419

PRIMARY PANCREATIC LYMPHOMA: CLINICAL PRESENTATION, DIAGNOSIS, TREATMENT AND OUTCOME IN A MULTICENTRIC ITALIAN EXPERIENCE

D. Facchinelli¹ | E. Boninsegna² | S. Sina³ |

A. Borin⁴ | M. Tisi⁵ | F. Piazza⁶ | G. Scapinello⁶ |

E. Maiolo⁷ | M. Merli⁸ | P. Stefani⁹ | M. Basso¹⁰ |

A. Parisi³ | E. Manfrin³ | M. Krampera¹ | C. Visco¹ |

C. Tecchio¹

¹Department of Medicine, Hematology Unit, Verona, Italy; ²Public Health, Radiology, Mantova, Italy; ³Diagnostics, Pathology and Diagnostics, Verona, Italy; ⁴Surgery, General and Pancreatic Surgery, Verona, Italy; ⁵Department of Medicine, Hematology Unit, Vicenza, Italy; ⁶Department of Medicine, Hematology Unit, Padova, Italy; ⁷Department of Medicine, Hematology Unit, Roma; ⁸Department of Medicine, Hematology Unit, Varese, Italy; ⁹Department of Medicine, Hematology Unit, Treviso, Italy; ¹⁰Department of Medicine, Hematology Unit, Castelfranco Veneto, Italy

**Introduction:** Primary Pancreatic Lymphoma (PPL) is a very rare disease, representing only 0.1% of lymphomas and 0.2% of pancreatic tumors. PPL presentation is variable and may overlap the onset of other neoplastic or inflammatory pancreatic diseases, often resulting in diagnostic difficulties. Due to the limited number of PPL study series, standardized diagnostic and therapeutic protocols are currently lacking.

**Methods:** Diagnostic criteria for PPL were established according to the "Fourth WHO Classification of digestive tumors". Clinical and treatment data of patients diagnosed with PPL between 2005 and 2018 were retrieved from medical record databases of 7 Italian Hematology Units. Overall survival (OS) and progression free survival (PFS) were calculated according the Kaplan Meier test and compared by the log-rank test.

**Results:** Overall 37 patients were affected by PPL. Clinical manifestations at diagnosis are summarized in the table. Most patients (83%) had a high grade B cell histotype. Fifty nine % of patients were first line treated with chemotherapy, 21% with chemo + radiotherapy, 10% with surgery + chemotherapy, 3% with surgery and 7% did not receive any treatment. With a median follow up of 37.5 months the 2 year OS is 59% while the 2 year PFS is 45%. Provided the relatively low number of cases, patients with low grade lymphomas and a good risk Revised International Prognostic Index (R-IPI) had better median OS (not reached vs 26 months and not reached vs 8 months, p=0.31 and 0.001) and PFS (not reached vs 108 months and 108 vs 8 months, p=0.095 and 0.01) as compared to the others. There were no differences in OS and PFS between chemotherapy or chemo-radiotherapy treatments (p=0.8 and 0.33) while patients who underwent debulking surgery (alone or + chemotherapy) had a significant worse OS as compared to those treated with chemotherapy alone (median not reached vs 6 months, p=0.033). Importantly 3/28 (10.7%) patients with high

grade PPL experienced a central nervous system (CNS) relapse of disease.

**Conclusions:** PPL represents a rare and difficult-to-recognize disease with symptoms and pancreatic gland localization superimposable to those of pancreatic ductal adenocarcinoma. Most PPL are high grade non Hodgkin lymphoma. According to our study biopsy should be the preferred diagnostic method since debulking surgery was associated

<table><caption>TABLE 1</caption><thead><tr><th>CHARACTERISTICS</th><th>n (%)</th></tr></thead><tbody><tr><td>Median age (years)</td><td>56 (15-79)</td></tr><tr><td>M/F</td><td>22/15</td></tr><tr><td>ECOG&gt;2</td><td>6 (17%)</td></tr><tr><td>Presenting symptoms</td><td></td></tr><tr><td>Abdominal pain</td><td>20 (55%)</td></tr><tr><td>Jaundice</td><td>17 (47%)</td></tr><tr><td>B symptoms</td><td>11 (30%)</td></tr><tr><td>Laboratory values</td><td></td></tr><tr><td>LDH &gt; upper limits</td><td>14 (40%)</td></tr><tr><td>Pancreatic amylase &gt; upper limits</td><td>16 (52%)</td></tr><tr><td>CA 19-9 &gt; 25 U/L</td><td>6 (24%)</td></tr><tr><td>Diagnostic method</td><td></td></tr><tr><td>Percutaneous biopsy</td><td>16 (43%)</td></tr><tr><td>Endoscopic biopsy</td><td>14 (38%)</td></tr><tr><td>Surgical biopsy</td><td>4 (11%)</td></tr><tr><td>Debulking surgery</td><td>3 (8%)</td></tr><tr><td>Pancreatic location</td><td></td></tr><tr><td>Head</td><td>25 (70%)</td></tr><tr><td>Body and Tail</td><td>11 (30%)</td></tr><tr><td>Mean diameter, mm (range)</td><td>83 (20-180)</td></tr><tr><td>Histology</td><td></td></tr><tr><td>DLBCL</td><td>19 (51%)</td></tr><tr><td>High grade B cell lymphoma NOS</td><td>10 (27%)</td></tr><tr><td>Follicular lymphoma</td><td>4 (11%)</td></tr><tr><td>Hodgkin lymphoma</td><td>2 (5%)</td></tr><tr><td>PTCL</td><td>1 (3%)</td></tr><tr><td>Burkitt lymphoma</td><td>1 (3%)</td></tr><tr><td>Clinicale stage</td><td></td></tr><tr><td>I-II</td><td>17 (48%)</td></tr><tr><td>III-IV</td><td>19 (52%)</td></tr><tr><td>Type of treatment</td><td></td></tr><tr><td>Surgery</td><td>1 (3%)</td></tr><tr><td>Surgery + Chemotherapy</td><td>3 (10%)</td></tr><tr><td>Chemotherapy</td><td>17 (59%)</td></tr><tr><td>Chemotherapy + Radiotherapy</td><td>6 (21%)</td></tr><tr><td>No treatment</td><td>2 (7%)</td></tr></tbody></table>
with a worse OS. The high CNS relapse rate suggests that patients
with high grade PPL should receive CNS directed prophylaxis.

**Keywords:** extranodal lymphomas.

420
SEQUENTIAL
CHEMOTHERAPY/RADIOTHERAPY WAS
SUPERIOR TO SANDWICH THERAPY FOR
PRIMARY EARLY-STAGE DLBCL OF
WALDEYER'S RING

X. Wang<fnref n="1" /> | Q. Zhou<fnref n="1" /> | S. Zhou<fnref n="1" /> | Z. Qian<fnref n="1" /> | L. Li<fnref n="1" /> | L. Qiu<fnref n="1" /> | X. Ren² | X. Liu<fnref n="1" /> | H. Zhang<fnref n="1" />

Immunology/Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

**Introduction:** Waldeyer's ring (WR) consists of lymphoid tissue located in the pharyngeal and tubal tonsils, which are at the pharynx to the back of the oral cavity and the base of the tongue, as well as in the palatine and lingual tonsils. Diffuse large B-cell lymphoma of Waldeyer's ring (WR-DLBCL) is an extremely rare malignancy, and radiotherapy (RT) can improve survival for early-stage WR-DLBCL patients. However, the superiority of sequential chemotherapy/radiotherapy (CT+RT) and sandwich therapy (ST) remains unclear.

**Methods:** Eighty-two primary early-stage WR-DLBCL patients treated with CT+RT, ST or chemotherapy (CT) alone were enrolled. Treatment response and patient survival were evaluated. The clinicopathological parameters impacting PFS or OS were analysed by univariate analyses. The Kaplan-Meier test was used to analyse survival.

<figure><img src="image_250.png" /><figcaption>Fig.1. Kaplan-Meier curves of primary early-stage WR-DLBCL patients treated with CT and RT (A, OS curves), CT and ST (B, OS curves), CT and CT+RT (C, OS curves), CT+RT and ST (D, OS curves), and CT+RT and ST (E, PFS curves)</figcaption></figure>

<footnote n="1">¹Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; ²Department of</footnote>
Independent prognostic factors for PFS and OS were further studied using multivariate analyses.

**Results:** The ORR of patients treated with CT+RT and ST were 100% and 95.2% respectively, which were higher than the ORR of patients treated with CT alone (100% vs 90.3% and 95.2% vs 90.3%). Complete response of patients treated with CT+RT tended to be better than that of patients treated with ST (70.0% vs 61.9%). Importantly, patients treated with CT+RT could maintain the higher CR rate than those treated with ST (73% vs 33.3%) and those treated with CT alone (73% vs 45.2%) during the long follow-up. Patients treated with CT+RT but not ST had significantly superior OS (P=0.003) to the survival of patients treated with CT alone. Patients treated with CT+RT experienced better outcomes than those treated with ST did (5-year PFS, 47.4% vs 23.8%, P=0.049; 5-year OS, 83.3% vs 50.0%, P=0.032). The univariate analysis showed that CT+RT treatment regimen was significantly associated with better survival.

**Conclusions:** CT+RT was superior to ST and improved the survival for primary early-stage WR-DLBCL patients.

**Keywords:** chemotherapy; diffuse large B-cell lymphoma (DLBCL); radioimmunotherapy (RIT).

421
PRIMARY THYMIC MUCOSA-ASSOCIATED
LYMPHOID TISSUE LYMPHOMA:
7 CLINICAL CASES REPORT AND A REVIEW
OF THE LITERATURE

W. Xu | D. Xu | L. Wang | H. Zhu | J. Liang |
J. Li

Hematology, the First Affiliated Hospital of Nanjing Medical
University, Jiangsu Province Hospital, Nanjing, China; Key Laboratory of
Hematology of Nanjing Medical University, Nanjing, China;

<figure><img src="image_251.png" /><figcaption>**Figure 1.** Pathological features of thymic MALT lymphoma</figcaption></figure>
Collaborative Innovation Center for Cancer Personalized Medicine,
Nanjing, China

**Introduction:** Mucosa-associated lymphoid tissue (MALT) lymphoma is one kind of non-Hodgkin lymphomas (NHL), accounts for 7% to 8%. MALT lymphoma is an indolent, organophilic lymphoma that can nearly occur at any epithelial tissues and mucosal sites. The predilection sites of MALT lymphoma are gastrointestinal tract, salivary glands, lungs and other organs. Studies have shown that MALT lymphoma is associated with chronic inflammation and antigenic stimulation, including chronic infection of pathogens and autoimmune disease. Primary thymus MALT lymphoma is rare. Only 92 cases have been reported over the past 27 years, and only 15 cases reported from China before. Here we introduce 7 cases of primary thymic MALT lymphoma found in the First Affiliated Hospital of Nanjing Medical University, and takes a review of the literature.

**Methods:** We analyze 7 cases of primary thymic MALT lymphoma in the First Affiliated Hospital of Nanjing Medical University from December 2017 to February 2019. We evaluate the clinical features, laboratory test results, PET-CT scans, pathological specimen stained by hematoxylin-eosin (HE) or immunohistochemistry, etc (Figure 1). The median follow-up of 7 cases is 8 months (range 1 to 15 months).

**Results:** primary thymic MALT lymphoma is a kind of indolent small lymphocytic lymphoma, appears mostly in Asian women and is often accompanied with AID. SS is the most common AID. Both contrast-enhanced CT and other imaging findings before surgery and pathological specimen after surgery can see mass with smooth boundary, containing cystic cavities of different sizes and numbers. We can also observe a wide range of small to medium-sized lymphocytes, with increased plasma cells surrounding small blood vessels. Primary thymic MALT lymphoma is lack of API2-MALT1 fusion gene. All cases only received "watch and wait" approach after surgery. Up to now, none of them had recurrence, and their quality of life was no different from normal people.

**Conclusions:** When clinicians meet female patient with thymic solid-cystic or cystic mass, together with AID, especially SS, and without any symptom of myasthenia gravis, we should take primary thymic MALT lymphoma into consideration.

**Keywords:** Mucosa-Associated Lymphoid Tissue (MALT); positron emission tomography (PET); thyroid function.

## 422
FIRST-LINE ADJUVANT RADIOTHERAPY IMPROVES PFS IN PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA - A RETROSPECTIVE ANALYSIS OF 102 PATIENTS FROM A SINGLE CENTER

D. Salek | A. Janikova | J. Michalka | E. Miculkova |
M. Hadrabova | F. Folber | Z. Kral | J. Mayer

Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic

**Introduction:** The cure rate of primary mediastinal large B-cell lymphoma (PMBL) in the rituximab era is about 80-90%, using CHOP-like or more intensive induction regimens (e.g. DA-EPOCH-R). The use of consolidative radiotherapy (RT) varies among centers, mostly being a standard of care until now. PMBL typically affects young population, with a female predominancy. Therefore, there are concerns about a long-term toxicity of RT, including secondary breast and lung cancer and heart failure. On the other hand, RT could improve the local disease control and maybe reduce the relapse rate. Prospective trials for this rare disease are sparse and the role of radiotherapy (RT) in the consolidation of remission remains unclear.

**Methods:** We have retrospectively analyzed data of 102 patients (pts) with newly diagnosed PMBL treated in our center between 2001-2017, with a median follow-up 6.8 years (range 0.1 – 17.7). The induction regimen was predominantly CHOP-like chemotherapy (94%) plus rituximab (94%). Disease status was assessed after 6 cycles of induction chemotherapy, using PET-CT and the Cheson 2007 criteria. The eventual consolidation with radiotherapy depended individually on the physician decision only.

**Results:** Median age was 35 years (women: men = 1.1:1). B symptoms were present at 54% of pts, elevated LDH in 90% and ECOG 2-4 in 27% cases; the most of pts had aalPI 1 (51%). Five-year overall survival (OS) and progression-free survival (PFS) of the entire group were 86% and 80%, with 16 relapses and 8 deaths. After induction chemotherapy, the response was evaluated in 94 pts, 75% of them achieved complete remission (CR), 15% partial remission (PR), and 9/94 (10%) had a stable disease or progression (SD/PD). The SD/PD pts had poor outcome with only 30% OS at 5 years. The role of radiotherapy was analyzed in 71 pts with CR, where 40 of them (56%) received radiotherapy (RT+ group) on mediastinum or residual mass (the dose 36-44 Gy), and 31 (44%) were observed without RT. We have found statistically significant difference in PFS in favor of subgroup with radiotherapy (5-year PFS 97% vs. 80%, p=0.03). There were only 2 relapses in the RT+ group, compared to 6 relapses in pts without RT, but this effect was not projected into OS (5-year OS 95% in RT+ vs. 90% in observation cohort, p= n.s.).

**Conclusions:** Our retrospective and non-randomized data evaluating the role of radiotherapy in the first-line consolidation show that patients reaching PET negative CR after R-CHOP induction displayed lower relapse rate and better PFS, but these facts do not impact the overall survival. These results should be confirmed in a larger prospective randomized trial.

**Keywords:** primary mediastinal large B-cell lymphoma (PMLBCL).

## 423
PREDICTIVE VALUE OF END-OF-TREATMENT POSITRON EMISSION TOMOGRAPHY SCAN AFTER DA-EPOCH-R IN PRIMARY MEDIASTINAL B-CELL LYMPHOMA. REAL-LIFE EXPERIENCE

E. Derenzini¹ | S. Ramadan¹ | A. Vanazzi¹ |
T. Radice¹ | D. Avenoso¹ | A. Mulè² |
<figure><img src="image_252.png" /><figcaption>Figure 1</figcaption></figure>

S. Sammassimo<fnref n="1" /> | F. Gigli<fnref n="1" /> | E. Iannitto<fnref n="3" /> |

U. Consoli<fnref n="4" /> | C. Patti<fnref n="2" /> | C. Tarella<fnref n="1" />

**Background:** In recent years DA-EPOCH-R has been shown to be very effective in primary mediastinal B-cell lymphoma (PMBCL), and available data suggest that this regimen could obviate the need of consolidative radiotherapy (RT). However, the available evidence is based on a limited number of studies, and the large scale applicability of these data needs to be confirmed. In this study, we report the data of a real-life experience with R-DA-EPOCH-R regimen.

**Methods:** Between 2013 and 2018, 44 patients (pts) affected by PMBCL were treated with 6 cycles DA-EPOCH-R + 2 additional Rituximab infusions at 2 italian institutions. Median age at initial diagnosis was 36 years (range 18-55), 29 pts were female (female/male ratio=1.8/1). Histology was centrally reviewed. Positron emission tomography (PET) scans were performed at least 1 month after last Rituximab infusion. 26 pts had stage I-II, 18 pts stage III-IV. All but one pts had bulky disease at diagnosis.

**Results:** All pts evaluable for response (n=40) completed the planned treatment, which is still ongoing in 4 pts (all pts completed ≥ 4 cycles). 30 pts (68%) experienced grade III-IV hematological toxicities. 4 pts (9%) had febrile neutropenia. Prophylactic G-CSF was given to all pts. Among patients who completed treatment, end of treatment positron emission tomography (EOT-PET) scan was negative (Deauville score 1-3) in 28 patients (70%) and positive (Deauville 4-5) in 12 pts (30%). 15 pts (37%) underwent consolidative RT, 8 of them were in complete remission (CR) after R-DA-EPOCH (these pts were enrolled in a randomized trial). Four-year estimated overall survival (OS) and progression free survival (PFS) rates of the whole cohort were 87% (2 events)

and 84% (5 events) respectively. Serial EOT-PET scans were performed in 5 patients, receiving 10 scans. None of the EOT-PET positive pts evaluated with serial PET scans progressed. A negative EOT-PET scan translated in a 100% PFS and OS rate, with no relapses observed after a median follow-up of 12 months (range 4-60). Among pts with positive EOT-PET scans, 4-year estimated PFS rate was 53% (p<0.01 vs PET negative), and 4-year estimated OS rate was 73% (p=0.07 vs PET negative), with all relapses/progressions occurring within 6 months from therapy completion (Figure 1). Only 8 of 28 EOT-PET negative pts (28%) received consolidative RT, which was given to 7 of 12 EOT-PET positive pts.

**Conclusions:** These data confirm a very high negative predictive value of EOT-PET in PMBCL treated with DA-EPOCH-R, with no patient relapsing after a negative EOT-PET, irrespective of consolidative radiotherapy (which was given in a minority of pts). Serial final PET scans could reduce unnecessary radiotherapy in a fraction of EOT-PET positive pts. These data support the use of DA-EPOCH-R in PMBCL, confirming that this regimen enables to spare radiotherapy in the majority of patients in real-life.

**Keywords:** DA-R-EPOCH; Deauville's criteria; primary mediastinal large B-cell lymphoma (PMLBCL).

**Disclosures:** Derenzini, E: Research Funding: TG-Therapeutics.

424

THE ROLE OF RITUXIMAB IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): A SYSTEMATIC REVIEW AND META-ANALYSIS

W. Lee<fnref n="1" /> | S. Go<fnref n="1" /> | O. Kwon<fnref n="2" />

<footnote n="1">¹Oncohematology, European Institute of Oncology IRCCS, Milan, Italy;</footnote>

<footnote n="2">²Hematology Division, Ospedale Villa Sofia-Cervello, Palermo, Italy;</footnote>

<footnote n="3">³Divisione di Oncoematologia, Casa di Cura la Maddalena, Palermo, Italy;</footnote>

<footnote n="4">⁴Division of Hematology, ARNAS Garibaldi, Catania, Italy</footnote>

<footnote n="1">¹Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea; ²Neurology, Gyeongsang National University School of Medicine, Jinju, Republic of Korea</footnote>
**Introduction:** For primary central nervous system lymphoma (PCNSL) a high-dose methotrexate (HD-MTX)-based combination chemotherapy with or without whole-brain radiotherapy (WBRT) has been the preferred front-line treatment since 2000, although no consensus exists for the most effective chemotherapy regimen until now. Now rituximab plus combination chemotherapy is also frequently used for these patients. In this study, we evaluated the survival benefit of addition of rituximab to HD-MTX-based combination chemotherapy for the patients with primary central nervous system lymphoma (PCNSL) by a systematic review with meta-analysis of clinical studies.

**Methods:** We searched the electronic databases, MEDLINE, EMBASE, COCHRANE, Web of Science, and SCOPUS to retrieve clinical studies evaluating benefit of rituximab on the patients with PCNSL. A total of 5 articles were included into qualitative systematic review. Two of them were used to conduct qualitative meta-analysis. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across studies using a random-effects model.

**Results:** The 5 finally selected studies compared the OS between R+ group and control group. The OS was reported by median months of PFS, HR with 95% CI, or percent of OS for 2 years Three of the 5 studies reported overall survival (OS) by median month, in which OS was longer in the R+ group (rituximab add-on group) than in the control group. The other two studies presented OS as HR with 95% CI; the HRs between R + group and control group were 0.63 (95% CI, 0.42-1.02), and 0.73 (95% CI, 0.35-1.52). The risk of heterogeneity was very low between the 2 studies: Q-value = 0.859, *p* = 0.354; I² = 0.000. When we combined the 2 studies with a fixed effect model, the pooling estimate of HR was 0.604 with 95% CI of 0.413 to 0.883 (*p* < 0.01).

**Conclusions:** This study suggests that the addition of rituximab to HD-MTX-based combination chemotherapy could prolong OS as well as PFS. The meta-analysis on PFS suggests that there was no significant heterogeneity between the studies.

**Keywords:** methotrexate (MTX); primary CNS lymphoma (PCNSL); rituximab.

## 425
TREATMENT OF BING NEEL SYNDROME: USING A SLEDGEHAMMER TO CRACK A NUT?

J.A. Bomsztyk<fnref n="1" /> | P. Jareonsettasin<fnref n="1" /> | A. Rismani<fnref n="1" /> |
S. Keddie² | A. Church² | M.S. Hart² | C. Hoskote³ |
I. Davagnanam³ | A.S. Carroll⁴ | M.P. Lunn² | S. D'Sa<fnref n="1" />

**Introduction:** Bing Neel syndrome (BNS) is a rare complication of Waldenström's Macroglobulinaemia (WM) comprising direct

infiltration of the CNS by lymphoplasmacytic lymphoma. Asymptomatic patients need active surveillance; symptomatic patients require treatment. Systemic and intrathecal chemo/immune therapy and BTK inhibitors are effective, but their optimum deployment remains unclear.

**Methods:** Data from 30 WM and 2 MZL patients with CNS involvement were extracted from the Rory Morrison Registry for WM; 5 with DLCBL histology were excluded. Diagnostic data are presented separately. Responses are reported as per Minnema et al. (2017).

**Results:** 27 patients with BNS were evaluated (16 female, 11 male). Median age at WM/MZL diagnosis was 62 (36 - 71) and BNS diagnosis was 68 (53 - 74). A median of 1 prior line of therapy was given for WM (range 0 - 7).

First line therapies for BNS: MATRix in 14 (54%) [4 cycles in 6, 3 cycles in 1, 2 cycles in 6 and 1 ongoing]; IDARAM in 6 (23%) [4 cycles in 2; 2 and 3 cycles in one each and 1 cycle in 2]; HD MTX +/- R +/- ARA-C was given in 3 (12%); IT MTX following systemic chemo in 1 (4%); Ibrutinib 1 (4%) and Fludarabine-R 1 (4%). The majority (74%) showed a partial response, with CR in 4 (15%).

In 9 (45%) patients, treatment was consolidated for different reasons (to limit toxicity, to deepen response): Rituximab in 3 (30%); Ibrutinib in 3 (30%); ASCT in 2 (20%); IT MTX in 2 (20%) and IT Rituximab in 1 (10%). Three patients (12%) had no response and 2 (8%) progressed through first line therapy; 2 (8%) patients are inassessible due to ongoing therapy.

Relapse occurred in 5 patients at a median time of 17 months (3 - 81); 4 (80%) patients received second line therapy all achieving a response (including 1 CR). Median overall survival from BNS diagnosis was not reached; 7/27 (30%) of patients have died; 3/7 (43%) from disease progression, 1/7 (14%) from sepsis during treatment, 1/7 (14%) treatment-unrelated, 1/7 (14%) unknown (likely disease progression). Of the 7 who died; median age at death 69 (55 - 74); median survival from diagnosis of WM/MZL 122 months (6 - 232); median survival from BNS diagnosis 3 months (0 - 13).

**Conclusions:** Our results suggest that the use of adapted intensive regimens +/- consolidation with Rituximab or BTK Inhibitor induces a prolonged remission with limited toxicity. Further investigation including a prospective multicentred clinical trial is required to help elucidate optimum treatment in BNS.

**Keywords:** BTK inhibitors; lymphoplasmacytic lymphoma (LPL); Waldenström's macroglobulinemia (WM).

## 426
BING NEEL SYNDROME: FIRST SUSPECT, THEN PROVE - A ROLE FOR CSF IgM ANALYSIS?

J.A. Bomsztyk<fnref n="1" /> | P. Jareonsettasin<fnref n="1" /> | A.S. Carroll² |
S. Keddie³ | A. Church³ | M.S. Hart³ | C. Hoskote⁴ |
I. Davagnanam⁴ | A. Rismani<fnref n="1" /> | M.P. Lunn³ | S. D'Sa<fnref n="1" />

<footnote n="1">¹Haematology, University College London Hospital, London, United Kingdom; ²Neuroimmunology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; ³Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; ⁴Brain and Mind Research Institute, University of Sydney, Sydney, Australia</footnote>

<footnote n="1">¹Haematology, University College London Hospital, London, United Kingdom; ²Brain and Mind Research Institute, University of Sydney, Sydney,</footnote>
Syndney, Australia; ³Neuroimmunology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; ⁴National Hospital for Neurology and Neurosurgery, Neuroradiology, London, United Kingdom

**Introduction:** Bing Neel syndrome (BNS) is a rare complication of Waldenström's Macroglobulinaemia (WM) comprising infiltration of the central nervous system by lymphoplasmacytic lymphoma. Clinical presentation is heterogeneous and the diagnosis rests on abnormal neurological, radiological and cerebrospinal fluid (CSF) / cellular features.

**Methods:** Data from patients seen in our Neurohaematology Clinic were extracted from the Rory Morrison Registry for WM. From a total of 30 WM and 2 MZL patients with CNS involvement, 5 with high grade transformation to DLCBL were excluded here.

**Results:** 27 patients with BNS were characterised; female 16, male 11. Median age at WM/MZL diagnosis was 61 (36 - 71) and at BNS diagnosis was 68 (53 - 74). Median time from WM/MZL to BNS diagnosis was 31 months (0 - 222); median time from first symptoms to BNS diagnosis 2 months (0 - 69). A median of 1 line (range 0 - 7) of therapy was given for WM/MZL.

Clinical presentation was heterogeneous: motor weakness 48%; par-aesthesia 44%; visual disturbance 33%; cognitive decline 30%; ataxia 30%; headache 19%; psychiatric 11%; seizures 11%. 74% patients had an MRI with contrast prior to diagnosis, of which 80% had diffuse involvement (93% leptomeningeal, 7% perivascular) and 45% had tumoral disease (33% localised, 66% multifocal; 85% had brain and 50% spinal).

At BNS diagnosis CSF analysis was usually abnormal (12/18 patients). The median white cell count 13.5/µl (range 0 - 434) and red cell count 5.5/µl (1 - 3000) and flow cytometry frequently uninformative; MYD88 L265P was seen in the CSF of 4 patients. 15 patients underwent detailed analysis of CSF IgM, IgG and Albumin at diagnosis. Mean CSF IgM was 19.8mg/L (0.57-310), CSF IgG 85mg/L (13 - 297) and CSF Albumin 1262mg/L (155 - 4950); mean IgM CSF: serum ratio was 4.9 (0.04 - 35.91; normal <0.04) and IgM index (IgM ratio corrected for albumin) 0.2 (0.002 - 0.79), normal <0.045.

The combination of elevated CSF IgM and elevated Serum IgM was evaluated in 15 cases of BNS vs 20 other clonal haematological disorders. This has an 86.7% sensitivity, 75% specificity, 72.2% PPV and 88.2% NPV (c²(1)= 13.04, p<0.001) for the detection of BNS, which in combination with other features is diagnostically useful, but seldom measured.

**Conclusions:** Our study confirms the significant heterogeneity in clinical presentation of BNS, radiological findings and relationship to WM disease, emphasising the need for robust diagnostic tools. The optimum treatment approach remains to be elucidated.

**Keywords:** lymphoplasmacytic lymphoma (LPL); Waldenström's macroglobulinemia (WM).

427
A PROSPECTIVE STUDY ON THE
CIRCULATION AND CENTRAL NERVOUS

SYSTEM AFTERPRIMARY CENTRAL
NERVOUS SYSTEM B CELL
LYMPHOMATREATMENT WITH
RITUXIMAB

T. Lin | C. Peng | S. Liu | H. Huang | Z. Wang |

C. Guo | Q. Ren | X. Fang | H. Hong | F. Li |

Y. Ying Tian

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, China, Guangzhou, China

**Introduction:** The use of Rituximab for the treatment of primary central nervous system lymphoma(PCNSL) is controversial, whether the Rituximab permeability of blood-brain-barrier(BBB) can be improved by craniotomy is unknown.

**Methods:** ImmunocompetentPCNSL patients newly diagnosed via craniotomy or stereotactic biopsy were enrolled and received Rituximab (375 mg/m², Q3w) treatment. Systemicnon-Hodgkin's B cell lymphoma (systemic-B-NHL) patients without CNS involvement as the control group. The trough concentrations of Rituximab (C<sub>RTX</sub>) and CD19 levels in cerebrospinal fluid (CSF) and plasma were analyzed by ELISA and flow cytometry methods during each treatment cycle. The efficacy and adverse effects were recorded. Trial registration: ChiCTR1900021415.

**Results:** From December 2016 to February 2018, 23 PCNSL and 12 systemic-B-NHL patients were enrolled. The C<sub>RTX-CSF</sub> in craniotomy PCNSL group (0.2430[0.0606, 0.5198]µg/ml) was significantly higher than those in stereotactic-PCNSL group (0.0846[0.0235, 0.1178]µg/ml, P=0.000) and systemic-B-NHL group (0.1058[0.0764, 0.1431]µg/ml, P=0.000). The BBB penetrability of RTX in craniotomy PCNSL group (1.15%[0.92%, 2.03%]) was nearly four times that in stereotactic-PCNSL group (0.40%[0.28%, 0.54%], P=0.000) and three times that in systemic-B-NHL group (0.49%[0.26%, 0.61%], P=0.000). No significant differences in the C<sub>RTX-CSF</sub> for BBB penetrability of RTX were observed between stereotactic-PCNSL and systemic-B-NHL groups. The time for CSF CD19 cell clearance in craniotomy PCNSL patients tended to be reduced compared with stereotactic-PCNSL patients. The CR and ORR rates of craniotomy PCNSL patients were 30% higher than those of stereotactic-PCNSL patients.

**Conclusions:** The BBB penetrability of RTX and the CSF C<sub>RTX</sub> are significantly improved in PCNSL patients diagnosed via craniotomy. Rituximab could be recommended for routine use in craniotomy PCNSL patients.

**Keywords:** CD20; rituximab.

428
FRONTLINE THERAPY RESULTS IN
UNSELECTED PRIMARY CNS LYMPHOMA
PATIENTS WITHOUT CONSOLIDATION HD
<figure><img src="image_253.png" /></figure>

## CHEMOTHERAPY FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANTATION

**J. Michalka** | **D. Salek** | **E. Miculkova** |

**M. Hadrabova** | **A. Janikova**

*Department of Internal medicine, Hematology and Oncology and Faculty of Medicine, Masaryk University and University Hospital, Brno, Czech Republic*

**Introduction:** Therapy results from large prospective clinical trials in primary CNS lymphoma (PCNSL) are influenced by restrictive inclusion and exclusion criteria. Herein we present frontline therapy results in unselected patients with PCNSL based on retrospective analysis from single center database over the past 17 years, when consolidation high-dose chemotherapy with autologous stem cell transplantation (ASCT) was not a standard therapeutic approach.

**Methods:** Between 2000 and 2017 we register 79 patients with newly diagnosed PCNSL, median age 64 years (31 - 84). Frontline regimen for patients ≤ 70 years was 5-7x MPV +/- rituximab. Consolidation therapy conceded 2 cycles of cytarabine for selected patients in complete remission instead whole brain radiation therapy (WB RT) up to 45 Gy. None of the patients had consolidation HD chemotherapy with ASCT.

**Results:** Chemotherapy was administered to 72 patients (91 %), in 71 % (51 pts.) MPV regimen +/- rituximab. The rest of the patients had single agent methotrexate or cytarabine or WB RT. Only 35 patients completed at least 5 cycles of MPV-based chemotherapy, the others failed to complete because of unacceptable toxicity or progressive disease. Median OS in the whole unselected cohort was 38 months, 2-year PFS was 40 % and median PFS 14 months. Response rates were evaluated only in the subgroup of 35 patients who completed at least 5 MPV-based chemotherapy. Median age was 57 years (31 - 70), ORR was 80 %, progression was seen in 5 patients (14%), 2 were unable to assess. In this subgroup of relatively fit patients 2-year PFS was 45 % and 2-year OS was 55 %. 10 patients in CR after frontline therapy did not undergo WB RT consolidation, but received 2 courses of single

agent cytarabine instead. 5 of them reached durable remission and in the other 5 late relapses occured with median PFS 31 months (12-72).

**Conclusion:** R-MPV frontline therapy for PCNSL patients is widely used and considered as relatively effective with expected and manageable toxicity profile. But significant portion of patients is unsuitable for this regimen, mainly because of age and poor condition. Despite limited data from our single center database, only about 2/3 of all of the newly diagnosed PCNSL patients were fit for MPV-based chemotherapy and only 2/3 of them completed at least 5 cycles, that means nearly 50 % of all of the new cases. Compared to results from prospective clinical trials, long term survival data in this subgroup of relatively fit patients consolidated without HD-chemotherapy and ASCT are worse. Consolidation therapy with single agent cytarabine instead WB RT was administered as an option for selected patients in complete remission to avoid delayed neurotoxicity. Despite some long term remissions, late relapses were frequent after cytarabine consolidation, and so this approach cannot be recommended. Clinical factors that could predict recurrences in this subgroup were not identified, but the number of patients is too small for appropriate evaluation.

**Keywords:** autologous stem cell transplantation (ASCT); primary CNS lymphoma (PCNSL).

## 429
### IMPACT OF SURGERY TYPE ON THE OVERALL SURVIVAL TIME OF PATIENTS WITH PRIMARY BRAIN LYMPHOMA

**E. Wasik-Szczepanek¹** | **A. Walter-Croneck¹** |

**A. Szczepanek¹** | **D. Szczepanek²**

¹Department of Haematooncology and Bone Marrow Transplantation, Medical University in Lublin, Lublin, Poland; ²Department of Neurosurgery, Medical University in Lublin, Lublin, Poland

**Introduction:** The primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin lymphoma (NHL) without any symptoms of
systemic disease. They constitute about 3% of the primary central nervous system (CNS) tumors and about 1% of all NHL. They are diagnosed in patients of all ages, most often in men between 60 and 70 years of age. Histologically, they form a very homogeneous group of lymphomas. The most common (> 95%) are diffuse B-cell large lymphomas (DLBCL) expressing CD20, CD19 and CD79a antigens, which are non-germinal B-cell like (non-GCB). The aim of the study was to assess the significance of neurosurgical procedure scope (total resection, partial resection, biopsy) on overall survival (OS) and progression free time (PFS).

**Methods:** A retrospective study included 50 patients with PCNSL. There were 22 (44%) women and 28 (56%) men, aged 20-87 (mean age 62). Functional status of every patient was assessed using the Karnofsky scale, neurological examination and magnetic resonance imaging (MRI) of the head were performed. The final diagnosis was based on histopathological examination of tissue material obtained during a stereotactic biopsy or total / partial tumor resection.

**Results:** The most frequently diagnosed histopathological type of primary brain lymphoma was DLBCL (46/92%). In the majority of patients, PCNSL was located in the hemispheres of the brain (28/56%) and the corpus callosum (10/20%). Biopsy was performed in 26 (52%), partial resection in 6 (12%) and complete resection in 18 (36%) patients. In the entire study group, median overall survival was 16 months (0-108 months), while progression-free survival was 7.5 months (0-98 months). There was no statistically significant relationship between OS and PFS and the type of neurosurgical procedure performed (total resection, partial resection, biopsy) and the number and location of lymphoma tumors.

**Conclusions:** The lack of significant impact of complete tumor resection on OS and PFS in patients with PCNSL indicates the justifiability of performing it only in a selected group of patients, singled out on the basis of the neurological status and the location of lesions in the CNS.

**Keywords:** primary CNS lymphoma (PCNSL).

PTCL AND NK/T CELL LYMPHOMAS

430
PRE-TREATMENT SERUM ALBUMIN LEVEL AS A MEANS OF IMPROVING PROGNOSTIC MODELS IN PERIPHERAL T-CELL LYMPHOMAS: A STUDY FROM THE LATIN AMERICAN GROUP OF LYMPHOMAS (GELL)

B. Beltrán¹ | V. Otero² | C. Peña³ | L. Fiad⁴ |
C. Mahuad⁵ | I. Perdomo⁶ | D.A. Castro Uriol¹ |
M.A. Torres Viera⁷ | M.L. Rodriguez⁸ | T. Chisesi⁹ |
F. Valvert¹⁰ | G. Ignacio¹¹ | C. Chiattone¹² |
L. Villela¹³ | H. Idrobo¹⁴ | N. Cristaldo² |
F. Warley² | G. Garate⁵ | S.R. Paredes¹ |

M. Cabrera³ | O. Bonell¹⁵ | L. Malpica¹⁶ |
E. Sotomayor¹⁷ | J.J. Castillo¹⁸

¹Department of Oncology and Radiotherapy, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru; ²Department of Hematology, Hospital Italiano de Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina; ³Hematology Department, Hospital del Salvador, Santiago de Chile, Chile; ⁴Hematology Department, Hospital Italiano de La Plata, Buenos Aires, Argentina; ⁵Department of Hematology, Hospital Aleman, Ciudad Autonóma De Buenos Aires, Argentina; ⁶Department of Hematology, Hospital San José de Bogotá, Bogotá, Colombia; ⁷Hematology Department, Universidad Central de Venezuela, Caracas, Venezuela; ⁸Hematology and Bone Marrow transplantation Group, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia; ⁹Department of Hematology, SOLCA, Guayaquil, Ecuador; ¹⁰Department of Hematology and lymphoma, Cancer Center INCAN, Ciudad de Guatemala, Guatemala; ¹¹Department of Hematology, IMSS (Instituto Mexicano del Seguro Social), Ciudad de Mexico, Mexico; ¹²Hematology Division, Santa Casa Medical School, Sao Paulo, Brazil; ¹³Hematology and blood bank Service, ISSSTESON, Hermosillo, Mexico; ¹⁴Hematology, Universidad del Valle, Cali, Colombia; ¹⁵Hematology, Nacional Institute of Cancerology, Bogotá, Colombia; ¹⁶Division of Hematology and Oncology, University of North Carolina, North Carolina, United States; ¹⁷Hematology, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; ¹⁸Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, United States

**Introduction:** Peripheral T-cell lymphomas (PTCL) are heterogeneous and aggressive malignancies recognized by the 2016 WHO classification. The goal of this study is to evaluate the prognostic role of pretreatment serum albumin level (PAL) in aggressive PTCL subtypeS in a cohort of patients from Peru, Argentina, Chile, and Colombia.

**Methods:** Patients with PTCL treated between January 1991 and December 2017 were analyzed. Diagnosis of PTCL was based on histological findings. Overall survival (OS) curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Uni and multivariate logistic and Cox regression analyses were performed.

**Results:** 425 patients with PTCL met inclusion criteria; 48% were peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 38% were adult T-cell leukemia/lymphoma (ATLL) and 18% where others (ie. anaplastic, angioimmunoblastic, NK/T cell, enteropathy-associated and hepatosplenic lymphoma). The median follow-up was 3.5 years. 54% were younger than 60 years, and 55% were men. An ECOG ≥1 was seen in 48%, B symptoms in 65%, clinical stage III-IV in 75%, and high LDH level in 55% of the patients. PAL was <3.5 g/dl in 56% of the patients. 52% were classified as high/high-intermediate IPI score (31% and 21%, respectively), and 61% as high/high-intermediate PIT score (28% and 33%, respectively). 75% of patients received systemic therapy (25% best supportive care).

The IPI score and PIT score were useful to discriminate the highest risk group. High/high-intermediate had worse survival than low/low-
<figure><img src="image_254.png" /></figure>

intermediate IPI score (HR 2.92, 95%CI, 2.13-4.01, p<0.001); and high/high-intermediate had worse survival than low-low intermediate PIT score (HR 2.63, 95% CI, 1.88-3.68, p<0.001). In the multivariate analysis, the ATLL group had worse survival than PTCL-NOS (HR 1.82, 95% CI, 1.32-2.50, p<0.001). PAL<3.5 had poor survival than PAL>3.5 (HR 1.82, 95% CI, 1.33-2.48, p<0.001). The median OS at 5 years was 1.5 years with Albumin >3.5 and 0.6 years with Albumin <3.5.

When combining PAL<3.5 g/dl and IPI score (IPI-alb), patients were stratified in 3 risk categories: IPI-alb 0 with a median OS of 3.5 years, IPI-alb 1 with 1 year and IPI-alb 2 with 0.4 years. The IPI-alb 1 had worse survival than IPI-alb 0 (HR 2.13,95% CI 1.38-3.28, p=0.001), and IPI-alb 2 had worse survival than IPI-alb 0 (HR 3.73, 95% CI, 2.43-5.71, p<0.001). When we combine PAL<3.5 g/dl and PIT score (PIT-alb), were also stratified in 3 risk categories: PIT-alb 0 with a

median OS of 3.5 years, PIT-alb 1 with 1 year and PIT-alb 2 with 0.4 years. The PIT-alb 1 had worse survival than PIT-alb 0 (HR 2.08, 95% CI 1.30-3.33, p=0.002), and PIT-alb 2 had worse survival than PIT-alb 0 (HR 3.38, 95% CI, 2.13-5.38, p<0.001).

**Conclusions:** The PAL<3.5 g/dl could add prognostic value and improve the already known prognostic models IPI and PIT scores in PTCL. These findings warrant validation in prospective studies.

**Keywords:** prognostic indices; T-cell lymphoma (TCL).

**Introduction:** Patients with peripheral T cell lymphomas (PTCLs) generally have a poor prognosis with conventional chemotherapy. Consolidation with autologous stem cell transplantation is an option for patients with PTCL. However, whether prospective or retrospective studies on the timing of autologous stem cell transplantation remains controversial. We cannot determine whether autologous stem cell transplantation is necessary in patients with PTCL achieving first complete remission (CR1) following induction chemotherapy, especially in

<figure><img src="image_255.png" /><figcaption>Fig 1. Progression free survival(PFS) stratified by consolidative strategy. K-M PFS plots for patients who underwent ASCT in CR1 following induction regimens versus patients who underwent observation and waiting during CR1(P=0.723).</figcaption></figure>
patients with low-risk group. Therefore, we compare prognosis of low-risk patients who underwent ASCT in CR1 following induction regimens and patients who underwent observation and waiting during CR1.

**Methods:** We completed a retrospective analysis for low-risk PTCL patients who underwent either observation or up-front ASCT during CR1 in our center between 1/1/2007 and 12/31/2018. In our study, patients with PTCL age ≤65 years (median age, 52 years) and IPI score 0-1 were included. Histologic subtypes include PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma a(AITL) and anaplastic lymphoma kinase-negative large cell lymphoma (ALK-negative ALCL). In addition, patients with cutaneous T cell lymphoma and anaplastic lymphoma kinase-positive large cell lymphoma (ALK-positive ALCL) were excluded. The probabilities of PFS was calculated by the Kaplan-Meier method and compared by a log-rank test. The estimated lymphoma of relapse was calculated using cumulative incidence.

**Results:** In our center, 42 patients met all inclusion and exclusion criteria. And 29 patients underwent observation and waiting in CR1, 13 patients underwent consolidative ASCT. In low-risk patients of PTCL, with a median follow-up of 22 months, estimated 2-year PFS and 5-year PFS in the observation group were 57.4% and 46.0%, respectively. Among ASCT recipients, the 2-year and 5-year PFS were 67.7% and 54.2%, respectively. When considering incidence of disease relapse, the 1-year cumulative incidence of relapse in the observation and ASCT groups was 20.3% and 32.3%, respectively. However, there were no difference between observation and ASCT groups.

**Conclusion:** In conclusion, for low-risk PTCL patients achieving CR1 following induction therapy, consolidative ASCT does not extend progression-free survival compared to observation. We favor proceeding to observe and wait because of high toxic of hematopoietic stem cell transplantation.

**Keywords:** autologous stem cell transplantation (ASCT); peripheral T-cell lymphomas (PTCL).

## 432
OUTCOMES IN THE TREATMENT OF PATIENTS WITH T-CELL NON-HODGKIN'S LYMPHOMAS. THE EXPERIENCE OF SINGLE INSTITUTION

E.A. Gracia Medina<fnref n="1" /> | B. Benitez Caballero<fnref n="1" /> |

Y. Cruz Camejo<fnref n="1" /> | T. González Madruga<fnref n="1" /> |

E. Vasquez Olazabal<fnref n="1" /> | J. Jimenez Galaimena² |

D. Alfonso Estevez³ | D. Sanchez Pérez³ |

D. Corrales Otero⁴ | K. Ramirez Fajardo⁴ |

L. Pomar Durruthy<fnref n="1" /> | L. Martinez Espinosa<fnref n="1" />

T-cell non-Hodgkin lymphomas (NHL) are uncommon neoplasms that account for only 10-15% of all NHL. Every year in Cuba are diagnosed around 850 new cases of NHL, 12% of them are classified as T-cell NHL. A descriptive and retrospective study was performed to characterize patients with T-cell non-Hodgkin lymphoma diagnosed and treated at the National Institute of Oncology and Radiobiology (INOR), in the period from 2008 to 2016.

Between 2008 and 2016, 557 NHL received primary treatment at INOR, 56 of them (10.1%) were diagnosed as T-Cell NHL. A median age at diagnosed was 57 years. Most frequent histologic subtypes were Peripheral T-Cell Lymphoma NOS (26.8%), Anaplastic Large Cell Lymphoma (23.2%) Cutaneous Anaplastic Large Cell Lymphoma (16.0%) and Primary Cutaneous T-cell Lymphoma (14.3%). Most of the patients were diagnosed in advanced stage III-IV (57.6%), and 40.4% had extranodal involvement. The more frequent treatment modality was chemotherapy (64.3%) followed by the combination of chemotherapy with radiotherapy (26.8%). Most of patients were treated with CHOP/like regimens. High response rates were achieved with the combination treatment (86.7%). The 5 years overall survival was 29.5% for all patients, and 36.4% for patients who received treatment (n=52). The 5 years overall survival (OS) rate was better for patients with low-low-intermediate IPI (45.0%); cutaneous T-Cell Lymphoma subtype (65.0%); Ann Arbor stage I-II (68.8% p=0.021); treated with combined modality (77.9% p=0.003), and with CHOEP regimen (63.3% p=0.031); and patients who achieved completed response after primary treatment (66.3% p=0.001).

This is the first report from a series of T-Cell NHL treated at INOR. Outcomes in the treatment were similar to data reported internationally. A better characterization of the lymphoma subtypes could let identified subgroups of patients with better prognosis.

**Keywords:** non-Hodgkin lymphoma (NHL); peripheral T-cell lymphomas (PTCL); T-cell lymphoma (TCL).

## 433
T-CELL LYMPHOMA IN THE ELDERLY PATIENTS. WHO IS YOUNG, OLD, AND ELDERLY?

A. Janikova<fnref n="1" /> | R. Chloupkova² | P. Klener³ |

K. Benesova³ | V. Campr⁴ | D. Belada⁵ |

A. Sykorova⁵ | V. Prochazka⁶ | N. Kopalova<fnref n="1" /> |

J. Hamouzova³ | J. Pirnos⁷ | J. Duras⁸ |

H. Mocikova⁹ | M. Trneny³

<footnote n="1">¹Medical Oncology Departement, National Institute of Oncology and Radiobiology, La Habana, Cuba; ²Pathology Department, National</footnote>

<footnote>Institute of Oncology and Radiobiology, La Habana, Cuba; ³Radiotherapy Department, National Institute of Oncology and Radiobiology, La Habana, Cuba; ⁴Radiology Department, National Institute of Oncology and Radiobiology, La Habana, Cuba</footnote>

<footnote n="1">¹Department of Internal Medicine - Hematology nad Oncology, University Hospital Brno, Brno, Czech Republic; ²Institute of Biostatistics and</footnote>
<table><caption>TABLE 1</caption><thead><tr><th rowspan="2"></th><th colspan="5">Age at diagnosis</th><th rowspan="2">Log rank<br>p-value</th></tr><tr><th>&lt; 60 years<br>(n = 435)</th><th>60- &lt;65<br>(n = 140)</th><th>65- &lt;70<br>(n = 111)</th><th>70- &lt;75<br>(n = 101)</th><th>≥ 75 years<br>(n = 119)</th></tr></thead><tbody><tr><th>Median OS (95% CI)</th><td>9.8 yrs (-)</td><td>2.6 yrs (1.3-3.9)</td><td>2.2 yrs (1.3-3.2)</td><td>2.2 yrs (1.0-3.5)</td><td>1.3 yrs (0.8-1.9)</td><td>&lt; 0.001</td></tr><tr><th>Median PFS (95% CI)</th><td>3.7 yrs (1.5-5.9)</td><td>1.0 yrs (0.7-1.3)</td><td>1.4 yrs (0.5-2.3)</td><td>1.0 yrs (0.6-1.4)</td><td>0.8 yrs (0.6-1.1)</td><td>&lt; 0.001</td></tr></tbody></table>

Analyses, Faculty of Medicine Masaryk University Brno, Brno, Czech Republic; ³1st Internal Clinic- Clinic of Hematology, First Medical Faculty, Charles University, and General University Hospital, Prague, Czech Republic; ⁴Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Faculty Hospital in Motol, Prague, Czech Republic; ⁵4th Department of Internal Medicine - Hematology, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Hradec Kralove, Czech Republic; ⁶Department of Hemato-Oncology, University Hospital Olomouc, Olomouc, Czech Republic; ⁷Department of Oncology, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic; ⁸Department of Haematooncology, University Hospital Ostrava and Medical Faculty of the Ostrava University, Ostrava, Czech Republic; ⁹Internal Clinic of Haematology, University Hospital Kralovske Vinohrady Prague and Third Faculty of Medicine, Charles University Prague, Prague, Czech Republic

**Introduction:** Ageing of lymphoma population becomes the medical problem with growing proportion of patients > 60 years. Moreover, the term "elderly" is vague comprising people old between 61 to more than 100 years. We decided to analyze prognosis of the T-cell lymphoma patients >60yrs and different age subgroups within this cohort.

**Methods:** We used CLSG (Czech Lymphoma Study Group) database (Govtrial NT 03199066) for the retrospective analysis, where the

cohorts of patients were compared according to their age at diagnosis (<60 yrs, 60-<65, 65-<70, 70-<75, and ≥ 75 yrs), in terms of baseline parameters, treatment and survival.

**Results:** In total, 906 patients with new systemic T-cell lymphoma diagnosed 1999-2015 were identified, including 471 (52%) pts >60 years, 140 (15%) pts between 60 and <65yrs, 111 (12%) pts between 65-<70yrs, 101 (11%) pts between 70-<75yrs and 119 (13%) pts ≥75 yrs. With the age increases proportion of ECOG 3-4 (9.6% vs. 11.7% vs. 12.7% vs. 15% vs. 21.8%), and especially in cohort ≥75yrs decreases frequency of B-symptoms (44.5% vs. 55.2% vs. 51.4% vs. 54.5% vs. 36.3%). Proportion of sex, stage, bone marrow infiltration, bulky disease, and extranodal involvement were similar across age-groups.

Systemic chemotherapy was administered in 83.4% vs. 87.1% vs. 84.7% vs. 86.1% and 63% pts, including CHOP like therapy in 36% vs. 55% vs. 47% vs. 57% vs. 29%, CHOEP was given in 18% vs. 13% vs. 13% vs. 2% vs. 2%, and more intensive regimens were administered in 18% vs. 10% vs. 1% vs. 0% vs. 0%. In the 1st-line, auto-SCT was performed in 16.3% vs. 13.6% vs. 1.8% vs. 0% vs. 0% pts, but alo-transplants in 1.4% pts <60yrs only.

Overall survival (OS) differs significantly among cohorts with median 9.8 vs. 2.2 vs. 2.2 vs. 2.6 vs. 1.3 yrs (Table; p<0.001). Further, we analyzed survival according to IPI in three cohorts (<60yrs vs. 60-<75yrs vs. ≥75 yrs). Survival differences remained significant in the IPI low

<figure><img src="image_256.png" /><figcaption>Figure</figcaption></figure>
risk patients with median not reached for group <60yrs, 11.4yrs (95% CI; 5.6-17.3) for age 60-<75yrs and 3.4yrs (95% CI; 0.6-6.3) for patients ≥75yrs (p<0.001). For higher IPI groups, there were no significant differences in OS and PFS among age-cohorts.

**Conclusions:** There is evident that elderly T-cell lymphoma patients (>60yrs) represent heterogenous population, where we can recognise the patients aged 60- <75yrs who share similar clinical characteristics and similar outcomes and patients ≥75 yrs with significantly worse prognosis. Interestingly, the cohort of patients 60- <75 yrs has similar survival regardless difference in the therapy intensity.

**Keywords:** elderly; peripheral T-cell lymphomas (PTCL); prognostic indices.

## 434 - WITHDRAWN

## 435
RANDOMIZED PHASE II STUDY OF CHOP VS. FRACTIONATED ICED IN TRANSPLANT-ELIGIBLE PATIENTS WITH PREVIOUSLY UNTREATED PERIPHERAL T-CELL LYMPHOMA: INTERIM RESULTS OF CISL1504

S. Kim¹ | J. Jo² | D. Yoon³ | J. Hong³ | Y. Do⁴ |
J. Yea⁵ | S. Lim⁶ | H. Shin⁷ | H. Lee⁸ |
H. Yhim⁹ | J. Yi¹⁰ | Y. Choi¹¹ | M. Kim¹² |
D. Yang¹³ | W. Lee¹⁴ | H. Kang¹⁵ | C. Suh³ |
W. Kim¹

¹Medicine, Samsung Medical Cneter, Seoul, Republic of Korea; ²Internal Medicine, Ulsan University Hospital, Ulsan, Republic of Korea; ³Oncology, Asan Medical Center, Seoul, Republic of Korea; ⁴Internal Medicine, Dongsan Medical Center, Daegu, Republic of Korea; ⁵Radiation oncology, Yeungnam University Medical Center, Daegu, Republic of Korea; ⁶Internal Medicine, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea; ⁷Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea; ⁸Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea; ⁹Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; ¹⁰Internal Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea; ¹¹Internal Medicine, Chungnam National University, Daejon, Republic of Korea; ¹²Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea; ¹³Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea; ¹⁴Internal Medicine, Inje University Busan Hospital, Busan, Republic of Korea; ¹⁵Internal Medicine, Korea Cancer Center Hospital, Seoul, Republic of Korea

**Introduction:** The induction chemotherapy followed by autologous stem cell transplantation (ASCT) is a current widely used treatment strategy for patients with previously untreated peripheral T-cell lymphoma (PTCL). However, it is still not clear whether anthracycline-

<table><caption>TABLE 1</caption><thead><tr><th></th><th>CHOP<br>n = 40 (%)</th><th>Fractionated<br>ICED<br>n = 41 (%)</th><th>p</th></tr></thead><tbody><tr><td>Characteristics at<br>diagnosis</td><td></td><td></td><td></td></tr><tr><td>Age, median (range)</td><td>55.9 years<br>(27-64)</td><td>55.9 years<br>(29-64)</td><td>0.561</td></tr><tr><td>Histologic subtype</td><td></td><td></td><td>0.483</td></tr><tr><td>PTCL-NOS</td><td>19 (48)</td><td>16 (39)</td><td></td></tr><tr><td>AITL</td><td>16 (40)</td><td>15 (37)</td><td></td></tr><tr><td>ALK-negative ALCL</td><td>2 (5)</td><td>6 (15)</td><td></td></tr><tr><td>EATL</td><td>2 (5)</td><td>3 (7)</td><td></td></tr><tr><td>Others</td><td>1 (2)</td><td>1 (2)</td><td></td></tr><tr><td>Gender</td><td></td><td></td><td>0.413</td></tr><tr><td>Male</td><td>26 (65)</td><td>23 (56)</td><td></td></tr><tr><td>Female</td><td>14 (35)</td><td>18 (44)</td><td></td></tr><tr><td>Stage</td><td></td><td></td><td>0.212</td></tr><tr><td>I/II</td><td>2/7 (23)</td><td>1/3 (10)</td><td></td></tr><tr><td>III/IV</td><td>18/13 (77)</td><td>15/22 (90)</td><td></td></tr><tr><td>Bone marrow<br>involvement</td><td></td><td></td><td>0.107</td></tr><tr><td>Presence</td><td>9 (23)</td><td>16 (39)</td><td></td></tr><tr><td>Absence</td><td>31 (77)</td><td>25 (61)</td><td></td></tr><tr><td>IPI risk</td><td></td><td></td><td>0.424</td></tr><tr><td>Low</td><td>9 (23)</td><td>9 (22)</td><td></td></tr><tr><td>Low-Intermediate</td><td>18 (45)</td><td>13 (32)</td><td></td></tr><tr><td>High-intermediate</td><td>6 (15)</td><td>12 (29)</td><td></td></tr><tr><td>High</td><td>7 (17)</td><td>7 (17)</td><td></td></tr><tr><td>Treatment outcomes</td><td></td><td></td><td></td></tr><tr><td>Response to induction<br>therapy</td><td></td><td></td><td>0.639</td></tr><tr><td>Complete response</td><td>18 (45)</td><td>23 (56)</td><td></td></tr><tr><td>Partial response</td><td>6 (15)</td><td>6 (15)</td><td></td></tr><tr><td>Stable disease</td><td>0</td><td>1 (2)</td><td></td></tr><tr><td>Progressive disease</td><td>13 (33)</td><td>8 (20)</td><td></td></tr><tr><td>Not evaluated</td><td>3 (7)</td><td>3 (7)</td><td></td></tr><tr><td>Completion of planned<br>ASCT</td><td></td><td></td><td>0.456</td></tr><tr><td>Completed</td><td>20 (50)</td><td>21 (51)</td><td></td></tr><tr><td>Failed to complete</td><td>18 (45)</td><td>15 (37)</td><td></td></tr><tr><td>Ongoing</td><td>2 (5)</td><td>5 (12)</td><td></td></tr><tr><td>Relapse or progression<br>or death</td><td></td><td></td><td>0.904</td></tr><tr><td>Occurred</td><td>22 (55)</td><td>22 (54)</td><td></td></tr><tr><td>Absence of event</td><td>18 (45)</td><td>19 (46)</td><td></td></tr><tr><td>Survival status</td><td></td><td></td><td>0.860</td></tr><tr><td>Alive</td><td>29 (72)</td><td>29 (71)</td><td></td></tr><tr><td>Dead</td><td>11 (28)</td><td>12 (29)</td><td></td></tr></tbody></table>
<figure><img src="image_257.png" /></figure>

based chemotherapies such as CHOP could be a standard induction therapy for PTCL. Thus, we conducted a randomized phase II study to compare the efficacy of CHOP with a non-anthracycline-based chemotherapy regimen, fractionated ICED in transplant-eligible patients with PTCL (NCT02445404).

**Methods:** Patients are randomized at a 1:1 ratio to receive either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone: n=69) or fractionated ICED (ifosfamide, carboplatin, etoposide, dexamethasone: n=69) every 3 weeks for 6 cycles. After the 6th cycle, patients achieving complete or partial response undergo high-dose chemotherapy (Bu-Cy-Etoposide) followed by ASCT. The randomization is done by histologic subtype and International Prognostic Index. The primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival (OS) and overall response rate (ORR). The interim analysis is planned after 41 cumulative events occur. If interim analysis shows less than 0.017 of P-value, the study will be terminated after declaring fractionated ICED is better than CHOP. If P-value is between 0.017 and 0.686, the study will continue to proceed.

**Results:** The interim analysis was performed after 44 events occurred, and the outcomes of 81 patients were analyzed (CHOP: n=40; Fractionated ICED: n=41). All patients had 2 or less than 2 of ECOG performance, and their characteristics at diagnosis was not significantly different (Table 1). PTCL-NOS (n=35) and AITL (n=31) accounted for 81% of patients. The complete response rate of ICED (23/41, 56%) was higher than CHOP (18/40, 45%), thus, the ORR of ICED (29/41, 71%) was higher than that of CHOP (24/40, 60%). The planned ASCT was done in a half of patients in each arm. At a median follow-up of

17.9 months (95% Confidence Interval [CI]: 13.4-22.4), the median PFS of ICED was 11.0 months (95% CI: 5.8-16.1), and it was not significantly different from that of CHOP (7.3 months; 95% CI: 3.8-10.7). There was no significant difference of OS between two arms, either (Figure 1).

**Conclusions:** The interim results did not show significant difference between CHOP and fractionated ICED. This study will be continued until the planned number of patients based on the study protocol.

**Keywords:** autologous stem cell transplantation (ASCT); induction treatment; peripheral T-cell lymphomas (PTCL).

436
A PHASE II STUDY OF THP (PIRARUBICIN)-COP THERAPY IN PATIENTS WITH NEWLY DIAGNOSED ADVANCED PTCL: THP-3 STUDY OF JAPAN HEMATOPOIETIC MALIGNANCY CLINICAL STUDY GROUP

M. Ogura<fnref n="1" /> | K. Ohmachi² | R. Suzuki³ | Y. Atsuta⁴ |

T. Ito⁵ | K. Ohyashiki⁶ | S. Yano⁷ | M. Hidaka⁸ |

K. Ando² | N. Fukuhara⁹ | Y. Morishita¹⁰ |

T. Suzuki¹¹ | K. Tsukasaki¹² | N. Kobayashi¹³ |

K. Tsukamoto¹⁴ | Y. Ozawa¹⁵ | K. Yamamoto¹⁶ |

T. Hotta¹⁷ | T. Kinoshita¹⁶

<footnote n="1">¹Hematology and Oncology/Hematology and Oncology, Kasugai Municipal Hospital/Nagoya Daini Red Cross Hospital, Kasugai/Nagoya,</footnote>
Japan; ²Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan; ³Oncology and Hematology, Shimane University Hospital, Izumo, Japan; ⁴Data Center, Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan; ⁵Hematology and Oncology, Anjyo Kosei Hospital, Anjo, Japan; ⁶Hematology, Tokyo Medical University, Tokyo, Japan; ⁷Clinical Oncology and Hematology, Jikei University School of Medicine, Tokyo, Japan; ⁸Hematology, National Hospital Organization, Kumamoto, Japan; ⁹Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan; ¹⁰Hematology and Oncology, Konan Kosei Hospital, Konan, Japan; ¹¹Hematology, Shiga Medical Center for Adults, Moriyama, Japan; ¹²Hematology, Nagasaki University Hospital, Nagasaki, Japan; ¹³Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan; ¹⁴Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan; ¹⁵Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan; ¹⁶Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan; ¹⁷President, Nagoya Medical Center, Nagoya, Japan

**Introduction:** Although a randomized phase III study demonstrated superiority of brentuximab vedotin (BV) with CHP than CHOP alone in patients with newly diagnosed CD30+ peripheral T-cell lymphoma (PTCL) in progression-free survival (PFS) and overall survival (OS), it has not yet been established whether CHP is the most appropriate chemotherapy combined with BV. And, CHOP is still a de fact standard of care in newly diagnosed CD30-negative (neg) PTCL. Thus, new treatment regimen or strategy has been awaited since the outcome of patients (pts) with CD30-neg PTCL treated with CHOP is still poor. Pirarubicin (THP) is, an anthracycline drug, which is not affected by the multidrug resistance mediating p-glycoprotein, and is less cardiotoxic than doxorubicin. THP exhibits activity against some doxorubicin-resistant cell lines. A multicenter phase II study was conducted to evaluate the efficacy and toxicity of THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) therapy in newly diagnosed PTCL by Japan Hematopoietic Malignancy Clinical Study Group.

**Methods:** Eligibility criteria were as follows; newly diagnosed PTCL including PTCL-not otherwise specified (NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL); clinical stage of bulky II, III or IV; aged 20 to 79 years (yrs); PS 0-2 by ECOG's scale. THP-COP {doxorubicin is replaced with pirarubicin (50mg/m² on Day1) in CHOP} was delivered every 3 weeks up to 8 cycles in younger pts less than 69 years, and 6 cycles in elderly pts aged 70 to 79 yrs. The primary endpoint was complete response rate (%CR) including unconfirmed CR (CRu). The planned sample size was 40 pts, which provided at least 80% power with the expected %CR of 55%, threshold of 35%, and a one-sided α of 5%.

**Results:** From October 2007 to December 2012, 41 pts with a median age of 63 (21-77) yrs were enrolled. The numbers of pts with PTCL-NOS, AITL and ALCL was 21 (51%), 14 (34%) and 6 (15%), respectively. The number of stage II bulky, III and IV was 2 (5%), 22 (54%) and 17 (41%), respectively. 44 % were International Prognostic Index high/intermediate or high risk. The %CR including %CRu and overall

response rate were 51.2% (90% CI; 37.4-64.9) which met the primary endpoint, and 70.7% (95% CI; 54.5-83.9), respectively. The PFS (Figure) and OS at 3 years (3-year PFS and 3-year OS) were 43.5% (95% CI; 27.5-58.4) and 62.9% (95% CI; 43.3-77.4), respectively. Most common Grade 4 toxicities were hematologic: %Grade 4 neutropenia and thrombocytopenia were 80.5% and 9.8%, respectively. Cardiac adverse events were observed in 2 patients with Grade 1 arrhythmia. No secondary malignancies were observed.

**Conclusions:** In pts with untreated advanced PTCL including PTCL-NOS, AITL and ALCL, THP-COP demonstrated high efficacy with durable PFS and OS and acceptable toxicity profiles. Further large-scaled randomized study to compare with CHOP is warranted.

**Keywords:** chemotherapy; peripheral T-cell lymphomas (PTCL).

**Disclosures:** Ogura, M: Consultant Advisory Role: Celltrion, MeijiSeika Pharma, Mundi Pharma; Honoraria: Celgene, MeijiSeika Pharma. Ohmachi, K: Honoraria: Kyowa Hakko Kirin, Eisai, Chugai, Pfizer, Takeda, Celgene, JanssenPharma, Meiji Pharma. Atsuta, Y: Honoraria: CHUGAI, KyowaHakko Kirin, Yakut, JanssenPharma. Ohyashiki, K: Consultant Advisory Role: Celegen KK; Honoraria: Novartis Pharma KK, Bristol-Myers Squibb KK, Celegen KK, Nippon Shinyaku, Dainippon Sumitomo KK, Phizer KK, Jansen pharmaceutical KK, Otsuka pharmaceutical KK, Taiho pharmaceutical KK, Alexion, MSD KK, Kyowa Hakko Kirin KK, Takeda KK; Research Funding: Kyowa Hakko Kirin KK, Chugai pharmaceutical KK, Novartis pharmaceutical KK, Jansen pharmaceutical KK, Asuterasu KK. Yano, S: Research Funding: Otsuka Pharmaceutical Co., Kyowa Hakko Kirin Co., Astellas Pharma Inc., Mochida Pharmaceutical Co., Chugai Pharmaceutical Co., Eli Lilly Japan K.K., Takeda, MSD, Pfizer, Teijin, Sumitomo Dainippon Pharma Co., Ono Pharmaceutical Co., Japan Airlines, Zenyaku Kogyo, Daichi Sankyo, Eisai, CSL Behring. Hidaka, M: Research Funding: Chugai. Ando, K: Research Funding: MeijiSeika Pharma, Kyowa Hakko Kirin, Takeda, Eisai. Tsukasaki, K: Consultant Advisory Role: Daiich-Sankyo, Ono Pharma, HUYA; Honoraria: Chugai Pharma, Celgene, Mundy Pharma, Kyowa-hakko/Kirin, Takeda; Research Funding: HUYA, Bayer, Celgene, Chugai Pharma, Eizai, AbbVie, Daiich-Sankyo. Tsukamoto, K: Research Funding: Kiowa-Kirin, Chugai, Astellas, Takeda, MSD, Pheizer. Yamamoto, K: Consultant Advisory Role: Astra-Zeneca, Celgene, Chugai, HUYA, Meiji Seika Pharma, Mundipharma, Ono, Otsuka; Honoraria: Bristol-Myers Squibb, Celgene, Chugai, Eisai, HUYA, Kyowa Hakko Kirin, Meiji Seika Pharma, Mochida, Mundipharma, Novartis, Ono, Otsuka, Pfizer, Sumitomo Dainippon, Takeda; Research Funding: AbbVie, ARIAD Pharmaceuticals, Astra-Zeneca, Bayer, Celgene, Chugai, Eisai, Gilead Sciences, MSD, Novartis, Ono, Solasia Pharma, SymBio, Takeda, Zenyaku. Hotta, T: Consultant Advisory Role: Symbio.

437
PROGRESSION FREE SURVIVAL AT
12 MONTHS AFTER FIRST-LINE THERAPY
IS ASSOCIATED WITH FAVOURABLE
OUTCOMES AFTER FIRST
RELAPSE/PROGRESSION IN PERIPHERAL T-
CELL LYMPHOMA
Y. Shirouchi<fnref n="1" /> | M. Yokoyama<fnref n="1" /> | T. Fukuta<fnref n="1" /> |
A. Nishihara<fnref n="1" /> | N. Inoue<fnref n="1" /> | H. Uryu<fnref n="1" /> | Y. Kusano<fnref n="1" /> |
N. Nishimura<fnref n="1" /> | Y. Mishima<fnref n="1" /> | N. Tsuyama² |
K. Takeuchi³ | Y. Terui<fnref n="1" />

¹Hematology-Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; ²Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; ³Pathology Project for Molecular Targets, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

**Introduction:** Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas accounting for 5-15% of non-Hodgkin lymphomas. Survival outcomes of PTCL after relapse/progression are poorly understood. We analyzed the survival outcomes of PTCL after first progression/relapse, and report on newly identified prognostic factors for relapse/refractory PTCL (RR-PTCL).

**Methods:** We identified 83 patients with newly diagnosed PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL) between 2005-2017 in our institution. We then analyzed 48 cases with either disease progression or relapse after first line therapy (PTCL-NOS n=33, AITL n=10, ALK- ALCL n=4, ALK+ ALCL n=1). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and further compared by subtypes. Moreover, the ROC approach was used to determine the cut-off in discriminating between patient outcomes, then OS and PFS were compared. Additionally, possible prognostic factors were compared by log rank test. Variables that remained significant in univariate analysis were incorporated in multivariate analysis using the Cox proportional hazard regression model to further investigate independent prognostic factors.

**Results:** 54 patients (65%) experienced progression/relapse after first line therapy. After excluding those who did not receive salvage treatment at our institution, we analyzed the remaining 48 cases of RR-PTCL. A majority of patients were treated with ICE (45.8%) or GDP (20.9%). Other treatment included DHAP (4.2%), mogamulizumab (4.2%), pralatrexate (2.1%), and romidepsin (2.1%) among others (20.9%). The overall response rate (ORR) and complete remission (CR) rates were 27.7% and 51.1%, respectively, with median OS of 14 months (95% CI: 9-27 months) and PFS of 4 months (95% CI: 2-8months). No significant difference was observed among subtypes. Patients with PFS of at least 12 months before relapse/progression had significantly longer PFS and seemingly longer OS (Figure 1). Multivariate analysis revealed that presence of B-symptoms (HR: 6.20 95% CI: 2.30-16.72, P<.001) was significantly associated with inferior OS, whereas achieving CR or partial remission (PR) from salvage therapy was associated with superior OS (HR 0.41, 95% CI 0.19-0.89, P=.002). CR or PR after first line therapy (HR 0.30, 95% CI:0.14-0.64, P=.001) as well as after second line therapy (HR 0.28, 95% CI:0.14-0.55, P<.001) were identified to be predictive of better PFS.

**Conclusions:** Prognosis of RR-PTCL remains poor. Achieving PFS at 12 months after first line therapy was associated with significantly superior survival after first relapse/progression. Response (CR or PR) to therapy could serve as proxy for longer OS as well as PFS, and achieving CR or PR from previous therapy was also associated with better PFS.

**Keywords:** anaplastic large cell lymphoma (ALCL); angioimmunoblastic T-cell lymphoma (AITL); peripheral T-cell lymphomas (PTCL).

**Disclosures:** Yokoyama, M: Consultant Advisory Role: Chugai-Roche Pharmaceuticals Co LTD. Nishimura, N: Consultant Advisory Role: Chugai-Roche Pharmaceuticals Co LTD. Mishima, Y: Consultant Advisory Role: Chugai-Roche Pharmaceuticals Co LTD. Terui, Y: Honoraria: Bristol-Myers Squibb, Celgene, Janssen, Novartis Pharma and Takeda Pharmaceutical Co LTD.

<figure><img src="image_258.png" /></figure>

438
RESPONSE TO BRENTUXIMAB VEDOTIN
BY CD30 EXPRESSION: RESULTS FROM
FIVE TRIALS IN PTCL, CTCL, AND B-CELL
LYMPHOMAS

D. Jagadeesh<fnref n="1" /> | S. Horwitz² | N.L. Bartlett³ |
R. Advani⁴ | E. Jacobsen⁵ | M. Duvic⁶ |
A. Gautman⁷ | S. Rao⁸ | M. Onsum⁸ | M. Fanale⁸ |
Y. Kim⁹

<footnote n="1">¹Hematology and Medical Oncology, Cleveland Clinic, Cleveland, United States; ²Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, United States; ³Department of Medicine, Oncology Division, Washington University School of Medicine, Siteman Cancer Center, Saint Louis, United States; ⁴Medicine-Med/Oncology, Stanford Cancer Institute, Stanford, United States; ⁵Division of Hematologic Malignancies, Dana-Farber Cancer Institute,</footnote>
<table><caption>TABLE 1 ORR by CD30 expression, n/N (%)</caption><thead><tr><th></th><th>Study</th><th>CD30≥10%</th><th>CD30&lt;10%</th><th>CD30=0</th></tr></thead><tbody><tr><td rowspan="2">PTCL</td><td>SGN35-012</td><td>10/22 (45)</td><td>4/12 (33)</td><td>2/6 (33)</td></tr><tr><td>35-IST-030*</td><td>NA</td><td>4/6 (67)</td><td>1/2 (50)</td></tr><tr><td rowspan="3">CTCL (MF)</td><td>ALCANZA</td><td>20/28 (71)</td><td>12/22 (55)</td><td>NA</td></tr><tr><td>35-IST-001</td><td>11/20 (55)</td><td>11/20 (55)</td><td>NA</td></tr><tr><td>35-IST-002</td><td>12/15 (80)</td><td>9/17 (53)</td><td>NA</td></tr><tr><td>B-cell lymphoma</td><td>SGN35-012</td><td>17/47 (37)</td><td>24/66 (36)</td><td>17/50 (34)</td></tr></tbody></table>

NA=not applicable

*interim analysis of non-registrational study

Boston, United States; ⁶Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, United States; ⁷Clinical Development, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals Limited, Cambridge, United States; ⁸Development, Seattle Genetics, Inc., Bothell, United States; ⁹Department of Dermatology, Stanford University School of Medicine, Stanford, United States

**Introduction:** Brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, has been evaluated in multiple trials in patients (pts) with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell lymphoma. We examined the ability of CD30 expression level to predict response to BV across these patient populations.

**Methods:** Data were integrated from 275 pts with PTCL, CTCL, and B-cell lymphoma treated with BV from 5 prospective clinical trials. Study SGN35-012 evaluated BV plus rituximab or BV monotherapy in pts with relapsed/refractory non-Hodgkin lymphoma. The ALCANZA study compared BV to physician's choice of methotrexate or bexarotene in pts with mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL). Three investigator-sponsored trials evaluated BV monotherapy in pts with relapsed PTCL, MF, and pcALCL (35-IST-030, 35-IST-001, 35-IST-002). Exploratory analyses were conducted to examine the relationship between CD30 expression and objective response rate (ORR) for pts with CD30 expression ≥10%, <10%, or undetectable (0%) by IHC (malignant cells or lymphoid infiltrate; local review).

**Results:** 143 pts had tumors with CD30 <10%, including 58/143 with undetectable CD30. Activity with BV was observed at all levels of CD30 expression, including CD30=0 (Table). Analysis of the interaction between CD30 and duration of response is ongoing and will be shown in the presentation.

**Conclusions:** CD30 expression levels ≥10%, <10%, or undetectable did not predict response to BV in a range of CD30-expressing lymphomas: Clinical responses occurred in pts with CD30 low and CD30 undetectable lymphomas. Limitations of IHC, the dynamic nature and heterogeneity of cell-surface CD30 expression, and multiple mechanisms of action of BV may all contribute to this observation.

**Keywords:** brentuximab vedotin; CD30; non-Hodgkin lymphoma (NHL).

**Disclosures:** Jagadeesh, D: Research Funding: Seattle Genetics, Regeneron, MEI Pharma, Debiopharm. Horwitz, S: Consultant Advisory Role: Celgene, Millennium, Kyowa Hakki Kirin, Seattle Genetics, ADC Therapeutics, Corvus Pharmaceuticals, Innate Pharma, miRagen, Portola Pharmaceuticals, Verastem, Takeda; Research Funding: Celgene, Seattle Genetics, Takeda, Kyowa Hakko Kirin, Aileron Therapeutics, ADC Therapeutics, Verastem, Forty Seven. Bartlett, N: Consultant Advisory Role: Pfizer, Kite Pharma, Seattle Genetics; Research Funding: Seattle Genetics, Pfizer, Genentech, Kite Pharma, Merck, Bristol-Myers Squibb, Celgene, Immune Design, Forty Seven, Affimed Therapeutics, Janssen, Pharmacyclics, Millennium, Gilead Sciences, Novartis, MedImmune, Dynavax. Advani, R: Consultant Advisory Role: Genentech/Roche, Bristol-Myers Squibb, Pharmacyclics, Gilead Sciences, Bayer, Cell Medical, Seattle Genetics, AstraZeneca, Autolus, Takeda; Research Funding: Millennium, Seattle Genetics, Genentech/Roche, Pharmacyclics, Janssen, Celgene, Agensys, Merck, Kura, Regeneron, Infinity Pharmaceuticals, Forty Seven. Jacobsen, E: Consultant Advisory Role: Merck, Janssen, Seattle Genetics; Research Funding: Celgene; Other Remuneration: Merck. Duvic, M: Employment Leadership Position: Celgene, Kyowa Hakko Kirin, Forty Seven, Aclaris Therapeutics, Soligenix, Seattle Genetics, Millennium Pharmaceuticals, Mallinckrodt, Precision Oncology, Medivir; Consultant Advisory Role: Clinical Care Options/NCCN, Concert Pharmaceuticals, miRagen, Celgene, Taiwan Liposome, Defined Health, Huron Consulting, Evidera, HUYA Bioscience International, Guidepoint Global, Lynx Group, Kiniksa, Cell Medica, Dr. Reddy's Laboratories, Array BioPharma, MedaCorp, Medscape, Jonathan Wood and Associates; Honoraria: Kyowa Hakko Kirin, Aclaris Therapeutics, Celgene, Array BioPharma, Millennium Pharmaceuticals Seattle Genetics, Mallinckrodt, Cell Medical; Research Funding: Eisai, Kyowa Hakko Kirin, Allos Therapeutics, Shape Pharmaceuticals, Oncoceutics, Seattle Genetics, Mallinckrodt, Soligenix, Rhizen Pharmaceuticals, MPI Research. Gautman, A: Employment Leadership Position: Takeda; Stock Ownership: Takeda. Rao, S: Employment Leadership Position: Seattle Genetics, Bristol-Myers Squibb; Stock Ownership: Seattle Genetics. Onsum, M: Employment Leadership Position: Seattle Genetics; Stock Ownership: Seattle Genetics. Fanale, M: Employment Leadership Position: Seattle Genetics; Consultant Advisory Role: Bayer, BMS, Merck; Stock Ownership: Seattle Genetics; Honoraria: Takeda. BMS. Merck. Spectrum; Research Funding: Gilead, Genentech, Medimmune, Merck, BMS, ADC Therapeutics. Kim, Y: Consultant Advisory Role: Seattle Genetics, Eisai, Actelion, Kyowa Hakko Kirin, Millennium, miRagen, Innate Pharma, Medivir; Research Funding: Seattle Genetics, Millennium, Eisai, Merck, Kyowa Hakko Kirin, Soligenix, Innate Pharma, Neumedicines, Forty-Seven, Portola Pharmaceuticals, Horizon Pharma, miRagen; Other Remuneration: Innate Pharma, UpToDate.

439
A PHASE II TRIAL OF BRENTUXIMAB VEDOTIN (BV) AND LENALIDOMIDE (LEN)
# IN RELAPSED AND REFRACTORY (R/R) CUTANEOUS (CTCL) AND PERIPHERAL (PTCL) T-CELL LYMPHOMAS: PRELIMINARY RESULTS OF A PHASE II TRIAL

B.M. William<fnref n="1" /> | A. Abbasi<fnref n="1" /> | Y. Huang<fnref n="1" /> | R. Larbi<fnref n="1" /> | R. Giali<fnref n="1" /> | L. Yang<fnref n="1" /> | J. Brammer<fnref n="1" /> | C. Grantier<fnref n="1" /> | C. Hoffman<fnref n="1" /> | S. Ayyappan<fnref n="1" /> | R. Baiocchi<fnref n="1" /> | N. Epperla<fnref n="1" /> | B. Christian<fnref n="1" /> | L. Alinari<fnref n="1" /> | K. Maddocks<fnref n="1" /> | C. Chung<fnref n="2" />

**Background:** Patients with r/r tumor stage CTCL and/or PTCL have a poor prognosis. BV is currently FDA approved for CD30 positive CTCL and anaplastic large cell lymphoma (ALCL) with single agent activity in additional PTCL subtypes. Len also has single agent activity in patients with r/r CTCL/PTCL. The safety of the combination was established in a phase I trial in patients with r/r diffuse large B-cell lymphoma which defined the dose for this single-center, open label phase II trial of the combination in r/r CTCL/PTCL

**Methods:** Patients with ≥ 1 line of systemic therapy, at least stage IB (for CTCL), and no prior progression on BV were eligible. Treatment consisted of BV 1.2 mg/kg IV and Len 20 mg PO daily q3 weeks for a maximum 16 cycles. After 7 patients were treated, we reduced Len to 10 mg given safety/tolerability concerns. Responses are assessed by the ISCL/EORTC Global response criteria (for CTCL) and Cheson year criteria (for PTCL). The effect of treatment on quality of life (QOL) is assessed by Skindex-16.

**Results:** As of March 12, 2019, 14 subjects were accrued to the trial; 10 with mycosis fungoides, 2 with Sezary syndrome, 1 with CD30+ lymphoproliferative disorder, and 1 with systemic ALK-ve ALCL. Median age was 60 (49-74) years and 79% were males. For patients with CTCL, 2 (15%) had stage IB, 7 (54%) IIB, and 4 (31%) had stage IVA disease with median baseline modified Severity Weighted Assessment Tool (mSWAT) of 65 (4.4-190). Median CD30+ positivity by visual immunohistochemistry was 7.5% (1-75) and 6 (43%) patients had large cell transformation. Median number of prior therapies was 5.5 (1-9). Grade 3 adverse events (AEs) were reported in 8/14 (57%) patients; including neutropenia (4), thrombocytopenia (1), bronchitis (1), dyspnea (1), abdominal pain (1), vertigo (1), DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome (1), urinary tract infection (1), and tumor flare (2). All AEs were possibly related to Len and recovered with no sequelae. No new or worsening neuropathy was reported. Median number of cycles received was 3.5 (1-13). Best response in 12 evaluable patients, who completed ≥ 2 cycles of treatment, included complete response=2 (17%), partial response=3 (25%), and stable disease=7 (58%) with overall response rate of 38%. Currently 10/14 patients discontinued treatment due to progression (5), grade 3 thrombocytopenia (1), DRESS syndrome (1), tumor flare (2), and abdominal pain (1). On an earlier analysis of

Skindex-16 scores, 4/6 (66%) evaluable patients with CTCL had >50% reduction in their Skindex-16 scores after 2 cycles of treatment.

**Conclusion:** These results demonstrate that BV + Len is safe, has clinical activity in a heavily pre-treated patient population, with a potential to positively impact QOL in patients with T-cell lymphomas. Len doses >10 mg daily are poorly tolerated in CTCL patients because of tumor flare. Recruitment of both CTCL and PTCL patients for this trial is ongoing.

**Keywords:** cutaneous T-cell lymphoma (CTCL); peripheral T-cell lymphomas (PTCL).

## 440
# SURVIVAL BENEFIT WITH NOVEL AGENTS IN PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMAS (PTCL): THE COLUMBIA UNIVERSITY EXPERIENCE

H. Ma<fnref n="1" /> | E. Marchi<fnref n="2" /> | B. Cheng³ | O.A. O'Connor<fnref n="2" />

**Introduction:** Peripheral T-cell lymphomas (PTCL) are a group of rare and heterogeneous diseases characterized by an unfavorable prognosis. Conventional chemotherapy (CT) is only marginally effective as derived from the management of aggressive B-cell lymphomas. Patients often relapse, and available FDA-approved novel agents (NA) for these patients include pralatrexate and histone deacetylase inhibitors (HDACI). In these analyses, we aim to determine if NA improve outcomes in our cohort of patients.

<table><caption>TABLE 1 Patient Characteristics</caption><thead><tr><th>Subtype</th><th>Count (%)</th><th>Median Age, years (range)</th><th>Median OS, years (95% CI)</th></tr></thead><tbody><tr><td>Adult T-Cell Leukemia Lymphoma (ATLL)</td><td>18 (16)</td><td>46 (15-72)</td><td>2.53 (0.81-5.25)</td></tr><tr><td>ALK+ ALCL</td><td>8 (7)</td><td>24 (2-61)</td><td>NR (0.83-NR)</td></tr><tr><td>ALK- ALCL</td><td>10 (9)</td><td>63 (44-76)</td><td>7.38 (0.46-NR)</td></tr><tr><td>Angioimmunoblastic T-Cell Lymphoma (AITL)</td><td>33 (29)</td><td>56 (28-88)</td><td>2.94 (1.3-9.96)</td></tr><tr><td>PTCL not otherwise specified (NOS)</td><td>24 (21)</td><td>46 (19-76)</td><td>3.6 (1.29-12.79)</td></tr><tr><td>Other</td><td>19 (17)</td><td>50 (8-82)</td><td>2.32 (0.91-11.2)</td></tr><tr><td>TOTAL</td><td>112</td><td>57 (2-90)</td><td>3.3 (2.26-6.75)</td></tr></tbody></table>

<footnote n="1">¹Hematology, The Ohio State University, Columbus, United States;</footnote>

<footnote n="2">²Dermatology, The Ohio State University, Columbus, United States</footnote>

<footnote n="1">¹Hematology/Oncology, New York Presbyterian Hospital - Columbia University Medical Center, New York, United States; ²Center for Lymphoid Malignancies, Columbia University Medical Center, New York, United States; ³Biostatistics, Columbia University Medical Center, New York, United States</footnote>
<figure><img src="image_259.png" /><figcaption>Figure 1. The survival curves for patients who achieved CR (line 1) to second line novel agents compared to those who did not (line 0), p=0.0033.</figcaption></figure>

**Methods:** Research was conducted in accordance with the Institutional Review Board at New York Presbyterian Hospital - Columbia University Medical Center. From 1994 to 2018, 112 patients with PTCL were treated and included in the analysis. Overall survival (OS) was calculated from the time of diagnosis to death from any cause. Kaplan-Meier curves were generated and compared based on the log-rank test. Cox proportional hazard models were used to investigate the association by adjusting for age, gender, diagnosis, and the type of treatments. The analysis was done in SAS version 9.4.

**Results:** Table 1 summarizes the subtypes of PTCL, median age, and median OS. First line therapies mostly consisted of CT such as CHOP, CHOEP, and EPOCH. Patients who did not achieve a complete remission (CR) with first line CT were at increased risk of death (HR 4.6, p<0.0001). This remained true after excluding ana-plastic large cell lymphoma (ALCL), which has a better prognosis (HR 4.0, p=0.0001). Second and third line therapies included platinum- and gemcitabine-based CT, clinical trials, and novel agents. Importantly, patients who did not achieve a CR with second line novel agents had increased risk of death compared to those who achieved CR (HR 11, p=0.019) as shown in Figure 1. Patients who did not undergo autologous or allogeneic stem cell transplant (ASCT) had increased risk of death (HR 1.2, p=0.0058), and this impact was stronger after removing patients with ALCL from analysis (HR 2.5, p=0.016).

**Conclusions:** Our data is consistent with historical data, where ALK+ ALCL did better compared to other subtypes of PTCL. Patients who received NA as second line therapy after relapse and achieved CR had a survival benefit. Novel agents can be efficacious in a the relapsed/refractory population with limited treatment options. We are currently finding new ways to combine NA upfront to shift the paradigm in the treatment of these heterogeneous diseases.

**Keywords:** histone deacetylase inhibitors; pralatrexate; T-cell lymphoma (TCL).

**Disclosures:** O'Connor, O: Consultant Advisory Role: Celgene (Data Safety Monitoring Committee), Millennium, Mundipharma Pharmaceuticals, and TG Therapeutics (Travel Support only); Research Funding: Affimed, Agensys, Celgene, Merck, Seattle Genetics, Spectrum, TG Therapeutics and Trillium Pharmaceuticals.

441
TREATMENT OF RELAPSED AND
REFRACTORY T-CELL LYMPHOMAS: FIRST
PAVLOV STATE MEDICAL UNIVERSITY OF
SAINT-PETERSBURG EXPERIENCE

E. Lepik | A. Kozlov | E. Borzenkova | Y. Zalyalov |

K. Lepik | E. Kondakova | V. Baykov | I. Moiseev |

N. Mikhaylova | B. Afanasyev
Raisa Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation, First Pavlov State Medical University of Saint-Petersburg, Saint-Petersburg, Russian Federation

**Introduction:** T-cell lymphomas represent rare and heterogeneous group of aggressive non Hodgkin lymphomas. There are currently no standards for the treatment of relapsed/refractory T-cell lymphomas (r/r PTCL). A number of novel therapy approaches are aimed for improvement of outcomes in patients with r/r PTCL. This report summarizes the First Pavlov State Medical University experience in the treatment of patients with T-cell lymphomas.

**Methods:** We analyzed data of 34 patients with r/r PTCL eligible for stem cells transplantation treated in First Saint-Petersburg state medical University from 2005 to 2018. Among them n8 with anaplastic large cell lymphoma (ALK+), n3 with anaplastic large cell lymphoma (ALK-), n4 with angioimmunoblastic T-cell lymphoma, n5 with hepatosplenic T-cell lymphoma, n1 with γδ T cell lymphoma and n13 with PTCL not otherwise specified (PTCL-NOS). The median age was 46 years (range 11 – 73 years).

Median time from initial diagnosis to relapse or progression after primary therapy was 6.7 months (1.8-41). Among all patients n18 (53%) had a primary chemoresistant disease, while the rest n14 (47%) had a relapse after initial treatment. All patients received at least one line of salvage chemotherapy. The treatment was tailored according to biological factors presented in patients. In 7 patients with CD30+ PTCL the brentuximab vedotine was used. One patient with ALK+ anaplastic lymphoma received ALK inhibitor crizotinib. One patient with γδ TCL and PD-L1 hyperexpression was treatment with nivolumab. Responses were consolidated with hematopoietic stem cells transplantation. Overall 16 patients undergo SCT: high dose chemotherapy with autologous stem cells transplantation was performed in 10 patients, 11 patients underwent allogeneic hematopoietic stem cells transplantation (among them 5 patients with relapses after auto-SCT).

**Results:** At the time of analysis, 25 patients remain alive. The median follow up of alive patients was 29 months (1,5-101 mo). The median overall survival was not reached and 2-year survival rate was 82%. The disease status at the last follow up was CR in 15 patients, PR in 3 patients and PD in 16. Among factors significantly associated with adverse prognosis was lower ECOG performance status at the time of diagnosis (p=0,03). Patients that had undergo salvage SCT showed significantly better disease status at the moment of last follow up: 12/16 (75%) were in CR, versus 3/18 (17%) in patients who did not undergo SCT. No difference was found in OS between relapsed and primary refractory patients (p=0,73).

**Conclusions:** The results of analysis show that introduction of novel agents and consolidation with high dose chemotherapy and auto-SCT or allo-SCT in selected cases may improve outcomes in patients with relapsed and refractory peripheral T-cell lymphomas. Brentuximab

based regimens may be successfully used as a bridge therapy before stem cells transplantation.

**Keywords:** allogeneic stem cell transplant (alloSCT); autologous stem cell transplantation (ASCT); T-cell lymphoma (TCL).

442

ANALYSIS OF PUBLISHED TREATMENT OPTIONS FOR RELAPSED OR REFRACTORY (R/R) PERIPHERAL T-CELL LYMPHOMA (PTCL): AN EVIDENCE BASED DECISION MAKING APPROACH

E. Marchi¹

K. Tobina²

D. Maruyama²

H. Nagai³

O.A. O'Connor¹

¹Center for Lymphoid Malignancies, Columbia University Medical Center, New York, United States; ²Department of Hematology, National Cancer Center Hospital, Tokyo, Japan; ³Hematology/Oncology Research, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

**Introduction:** PTCL are rare diseases with a poor prognosis. Front line therapy achieves CR in 30% to 60% and OS of 25%. Patients with R/R disease have an even worse prognosis. There is no consensus on the management of R/R disease because evidence supporting most treatment approaches is modest. Many approaches are often not supported by literature, and categorizations regarding efficacy and toxicity without attention to details are ignored. Treatments that have achieved regulatory approval with stringent independent assessment of pathology and response are viewed as less established, or equivalent to smaller published experiences. In the effort to take a critical and comprehensive evidence-based approach to available standards in R/R PTCL we developed an objective scoring system for all types of studies published in the literature (eg randomized phase 3, case match control, phase 2, phase 1, case reports and small series) to aid decision-making based on an assessment of all the available data.

**Methods:** We performed an extensive review on PubMed of the clinical trials published in the literature that included patients with R/R PTCL. We proposed a rigorous scoring system based on a survey from nearly 100 authorities in the field to assess the scientific impact of each study based on the agreed study characteristics, including type of study (ie, randomized phase 3, case match control analysis, phase 2 weighted based on number of PTCL patients [> 100 vs < 100 patients], phase 1 with > 5 or < 5 PTCL patients enrolled, and retrospective) weighted based on percent of PTCL patients included; weighting for inclusion of central pathology or response review; weighting for detailed reporting of study metrics (ORR, CR, DoR, PFS). The scoring system included a penalty of - 0.5 each for ORR, DoR, or PFS not being reported and -0.2 for omitting previous lines of therapy. Studies that ranked 0 or below
were all grouped under the minimum score of 0. The proposed scoring system was evaluated by a panel of experts belonging to different academic institutions in three different continents, actively involved in T-cell lymphoma clinical research. The scoring system was modified accordingly based on recommendations made by 2 or more of the panel members.

**Results:** We identified 58 publications between 2004 and 2018. The scoring system spanned from 0 to 9. Only 12 of the 58 studies had a score above 5; 15 of 58 had a score between 1 - 5; remaining publications scored 0 - 1.

**Conclusion:** Our analysis suggests practice patterns are based on studies with low priority scores, and underweight robust clinical experiences. This analysis aims to produce an evidenced based approach for R/R PTCL.

**Keywords:** chemotherapy; peripheral T-cell lymphomas (PTCL).

443

AGGRESSIVE NK CELL LEUKEMIA: CLONALITY, CLINICAL AND GENETIC FEATURES

Q. Sun<fnref n="1" /> | Z. Qiu<fnref n="2" /> | Y. Wang<fnref n="1" /> | M. Wang³ |

L. Wang<fnref n="1" /> | Y. Wu<fnref n="1" /> | C. Qiao<fnref n="1" /> | H. Zhu<fnref n="1" /> |

W. Wu<fnref n="1" /> | J. Wu<fnref n="1" /> | Y. Xia<fnref n="1" /> | Y. Miao<fnref n="1" /> | L. Cao<fnref n="1" /> |

W. Xu<fnref n="1" /> | L. Fan<fnref n="1" /> | J. Li<fnref n="1" />

**Introduction:** Aggressive natural killer cell leukemia (ANKL) is an extraordinary rare aggressive malignancy of NK cells, but is relatively common in Asian. The accurate diagnosis of ANKL remains a great challenge. This study intends to describe the clonality, clinical and genetic features of ANKL and guide the diagnosis of this disease.

**Methods:** A total of 45 consecutive newly diagnosed ANKL patients were recruited from the First Affiliated Hospital of Nanjing Medical University, and clinical data were collected. Cytological morphology, flow cytometric analysis including killer cell immunoglobulin-like receptors (KIR), karyotypic analysis and molecular biology tests were used to diagnose and assess the monotypic clonality of NK cells. Survival analyses were done to verify the prognostic predictors of ANKL.

**Results:** All patients were adults, with a median age of 39 years (range 8-80 years) and a male: female ratio 1.4:1 (Table 1). B symptoms and fever were noted in all patients. Splenomegaly (91.1%) and hemophagocytic lymphohistiocytosis (HLH) (80.0%) were also

<table><caption>**TABLE 1** Clinical and biological characteristics of 45 patients with ANKL</caption><thead><tr><th>Characteristics</th><th>Number of Patients</th><th>%</th></tr></thead><tbody><tr><td><strong>Gender</strong></td><td></td><td></td></tr><tr><td>Male</td><td>26</td><td>57.8</td></tr><tr><td>Female</td><td>19</td><td>42.2</td></tr><tr><td><strong>Performance status (ECOG)</strong></td><td></td><td></td></tr><tr><td>0-2</td><td>22</td><td>48.9</td></tr><tr><td>3-4</td><td>23</td><td>51.1</td></tr><tr><td>LDH>250U/L</td><td>43</td><td>95.6</td></tr><tr><td>β2-MG>3.0mg/L (n=28)</td><td>26</td><td>92.9</td></tr><tr><td>Lymphocytosis</td><td>9</td><td>20.0</td></tr><tr><td>Neutropenia</td><td>20</td><td>44.4</td></tr><tr><td>Anemia</td><td>24</td><td>53.3</td></tr><tr><td>Thrombocytopenia</td><td>37</td><td>82.2</td></tr><tr><td><strong>Initial presentation</strong></td><td></td><td></td></tr><tr><td>Fever</td><td>45</td><td>100</td></tr><tr><td>Hepatomegaly</td><td>21</td><td>46.7</td></tr><tr><td>Splenomegaly</td><td>41</td><td>91.1</td></tr><tr><td>Hemophagocytic lymphohistiocytosis</td><td>36</td><td>80.0</td></tr><tr><td>Pleural effusion/ascites</td><td>24</td><td>53.3</td></tr><tr><td>EBV-DNA>5000copies/ml (n=38)</td><td>34</td><td>89.5</td></tr></tbody></table>

common. Most patients (34/38) were confirmed with EBV infection. Immunophenotyping of the ANKL cells were typically positive for CD2 and CD3, and CD7, CD16 and CD56 were positive for 66.7%, 52.9% and 87.8%, respectively. Either monotypic (n=8) or complete lack (n=20) of KIR expression was observed in 28 ANKL patients (Figure 1). Highly complex karyotypes were detected in five cases. No patient had clonal rearrangement of the T-cell receptor gene, and only one patient had STAT3 mutation. Median overall survival of ANKL patients was 27 days. HLH (P<0.001), pleural effusion/ascites (P=0.003), absolute lymphocyte count ≤4.0×10⁹/L (P<0.001), neutropenia (P=0.001), thrombocytopenia (P=0.009), positive EBV-DNA (P=0.036), positive CD56 (P=0.035), and performance status >2 (P<0.001) were identified as unfavorable factors of early death.

**Conclusions:** Our findings suggest that ANKL is a highly aggressive leukemia with high mortality. Detection of immunophenotyping and KIR may have important diagnostic value. More studies are needed to obtain a better understanding of the pathogenesis of this disease.

Complete lack of KIR antigens was observed in ANKL patient 20. The expression of KIR was evaluated by gating on the total population of CD3⁻ and CD56⁺ NK cells.

**Keywords:** Epstein-Barr virus (EBV); non-Hodgkin lymphoma (NHL).

<footnote n="1">¹Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China;</footnote>

<footnote n="2">²Department of Oncology, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, China; ³Department of Hematology, Nanjing First Hospital, Nanjing, China</footnote>
<figure><img src="image_260.png" /><figcaption>**Figure 1.** Representative tetramer staining of ANKL by FCM analysis</figcaption></figure>

444
CLINICAL OUTCOMES IN PATIENTS WITH
EPSTEIN-BARR VIRUS (EBV)-POSITIVE
NON-B CELL LYMPHOMA AT THE OHIO
STATE UNIVERSITY JAMES
COMPREHENSIVE CANCER CENTER (OSU
JAMES CCC)

J.E. Brammer¹ | P. Shindiapina¹ | A. Freud¹ |

C. Weigel¹ | C. Oakes¹ | A. Mishra² |

B. Mundy-Bosse¹ | P. Porcu² | R. Baiocchi¹

¹Hematology, The Ohio State University James Cancer Center, Columbus, United States; ²Oncology, Thomas Jefferson University, Philadelphia, United States

**Background:** EBV+ lymphomas, including extranodal NK/T-cell lymphoma (ENKTL), and EBV+ peripheral T cell lymphoma (PTCL) are rare, aggressive forms of non-Hodgkin lymphoma. EBV exhibits a restricted tropism for infecting naïve B lymphocytes; consequently, its oncogenic activity is most frequently associated with B cell lymphomagenesis. Given the rarity of EBV+ non-B cell lymphomas, there are no evidence-based treatment guidelines available. Here we
<table><caption>**TABLE 1** Patient Characteristics</caption><thead><tr><th></th><th></th></tr></thead><tbody><tr><td><strong>Demographics</strong></td><td>n/N (range or %)</td></tr><tr><td>Female</td><td>15/28 (54%)</td></tr><tr><td>Median age</td><td>58 (37-84)</td></tr><tr><td>Median ECOG</td><td>1 (0-3)</td></tr><tr><td><strong>Diagnosis</strong></td><td>n/N (range or %)</td></tr><tr><td>ENKTL</td><td>10/28 (36%)</td></tr><tr><td>PTCL AITL</td><td>9/28 (32%)</td></tr><tr><td>PTCL NOS</td><td>8/28 (29%)</td></tr><tr><td>Adult T cell leukemia/lymphoma</td><td>1/28 (4%)</td></tr><tr><td><strong>Disease characteristics</strong></td><td>n/N (range or %)</td></tr><tr><td>Median IPI</td><td>3 (1-5)</td></tr><tr><td>Stage III-IV</td><td>17/25 (58%)</td></tr><tr><td>LDH elevated</td><td>22/28 (79%)</td></tr><tr><td>Beta-2-microglobulin elevated</td><td>9/13 (69%)</td></tr><tr><td>Bone marrow involvement</td><td>7/24 (29%)</td></tr><tr><td>Peripheral blood involvement</td><td>5/20 (25%)</td></tr><tr><td>EBV viral load detectable</td><td>14/25 (56%)</td></tr><tr><td><strong>First line treatment</strong></td><td>n/N (range or %)</td></tr><tr><td>CHOP w/wo rituximab</td><td>7/28 (25%)</td></tr><tr><td>EPOCH</td><td>6/28 (21%)</td></tr><tr><td>SMILE (for ENKTL only)</td><td>7/28 (25%)</td></tr><tr><td>GELOX or GEMOX (for ENKTL only)</td><td>3/28 (1%)</td></tr><tr><td>Other systemic treatment</td><td>5/28 (14%)</td></tr><tr><td>Radiation therapy (Stage I-II only)</td><td>5/28 (18%)</td></tr><tr><td><strong>Response to first line treatment</strong></td><td>n/N (%)</td></tr><tr><td>CR</td><td>15/25 (60%)</td></tr><tr><td>PR</td><td>7/25 (28%)</td></tr><tr><td>No response</td><td>3/25 (12%)</td></tr></tbody></table>

report an analysis of clinical outcomes and prognostic factors of EBV+ non-B-cell lymphoma at OSU James CCC.

**Methods:** Data were collected by retrospective chart review and all diagnoses were established by a hematopathologist with investigator review. Univariate probabilities of overall survival (OS) and progression-free survival (PFS) were estimated utilizing the Kaplan-Meier method using IBM SPSS v 24.0. The log-rank test was utilized to assess for differences between groups in regard to OS and PFS.

**Results:** 28 patients, with a median follow-up time of 18 months, were treated for EBV+ non-B cell in 2014-2018. 10/28 (36%) had ENKTL and 17/28 (61%) had PTCL with 1 Adult T-cell lymphoma. Details of the patient demographics, disease characteristics and details of first-line therapy are listed in Table 1. OS for the entire cohort was 80% and 46% at 1 and 3 years. At 1 and 3 years, OS for PTCL was 80% and 41%, and 56% for ENKTL. Patients received a median of 2 lines of therapy. Response rate to frontline therapy was 88%, with 60% CR. OS was improved for patients who achieved a CR to first-line therapy (79% vs 33%) at 1 year and 66% vs 11% at 3 years, (p=0.004), Statistical significance was maintained within the ENKTL and PTCL disease cohorts. PFS for the entire patient cohort was 73%

and 27% at 1 and 3 years. PFS for ENKTL was 56% at 1 and 3 years, and PFS for PTCL was 59% and 16% at 1 and 3 years. PFS was improved in patients with IPI score of 1-2 vs 3-4 (PFS 75% vs 33% at 1 year, p=0.044). There was no significant association of sex, age, stage, EBV viral load, LDH elevation, absolute CD4 or CD8 counts and bone marrow involvement with either OS or PFS.

**Conclusions:** EBV-associated ENKTL and PTCL have similar OS and PFS rates with EBV+ PTCL outcomes similar to previously reported 5-year OS international PTCL consortium) expected for patients with PTCL. Sensitivity of EBV+ non B-cell lymphomas to chemotherapy and attainment of CR to first line of therapy was critical to achieving longer OS duration irrespective of disease type. Novel treatment approaches for patients with these rare histologic subtypes of lymphoma is clearly needed.

**Keywords:** Epstein-Barr virus (EBV); extranodal lymphomas; peripheral T-cell lymphomas (PTCL).

**Disclosures:** Brammer, J: Research Funding: Viracta: Clinical trial only.

Porcu, P: Research Funding: Viracta; clinical trial.

445

TREATMENT AND OUTCOMES OF PATIENTS WITH NK/T-CELL LYMPHOMA TREATED WITH MODIFIED (m)SMILE AND INTENSITY-MODULATED RADIOTHERAPY (IMRT), A SINGLE CENTER EXPERIENCE

P. Ghione¹ | S. Qi² | B.S. Imber³ |

S. Venkatraman⁴ | A. Moskowitz¹ | N. Galasso¹ |

M. Lunning⁵ | D. Straus¹ | C. Sauter⁶ | P. Dahi⁶ |

A. Dogan⁷ | J. Yahalom³ | S.M. Horwitz¹

¹Lymphoma Service, Memorial Sloan Ketterin Cancer Center, New York, United States; ²Radiation Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Shi, China;

³Department of Radiation Oncology, Memorial Sloan Ketterin Cancer Center, New York, United States; ⁴Department of Epidemiology and Biostatistics, Memorial Sloan Ketterin Cancer Center, New York, United States; ⁵Oncology and Hematology, University of Nebraska Medical Center, Omaha, United States; ⁶Bone Marrow Transplant Service, Memorial Sloan Ketterin Cancer Center, New York, United States;

⁷Hematopathology Service, Memorial Sloan Ketterin Cancer Center, New York, United States

**Introduction:** Extranodal NK/T cell lymphoma (ENKTL) is a rare subtype of lymphoma, poorly responsive to anthracycline-based chemotherapy. Treatment and prognosis are largely driven by stage, and the PINK and PINK-E scores appear to further refine it. Outcomes for patients with ENKTL have improved with L-asparaginase containing regimens into combined modality approaches. Based on the reported efficacy of SMILE (Yamaguchi, Cancer Sci, 2008), in 2009, we adopted a modified (m)SMILE (dexamethasone, methotrexate, ifosfamide, peg-asparaginase, etoposide) regimen given every 3 weeks, followed by
Localized (Nasal cavity only treatment)

<figure><img src="image_261.png" /></figure>

<figure><img src="image_262.png" /></figure>

<figure><img src="image_263.png" /></figure>

<figure><img src="image_264.png" /></figure>

<figure><img src="image_265.png" /></figure>

Dose (cGy)

<figure><img src="image_266.png" /></figure>

Locally advanced (Nasal cavity, nasopharynx and paranasal sinus treatment)

<figure><img src="image_267.png" /></figure>

<figure><img src="image_268.png" /></figure>

<figure><img src="image_269.png" /></figure>

<figure><img src="image_270.png" /></figure>

<figure><img src="image_271.png" /></figure>

Dose (cGy)

<figure><img src="image_272.png" /></figure>

radiotherapy (RT) as our standard approach. Main differences from the SMILE are: I) shorter course of chemotherapy, II) the use of peg-asparaginase (most common dose was 1500 U/m2), and III) lower dose and Intensity-Modulated Radiotherapy (IMRT) consolidation.

**Methods:** We retrospectively analyzed 28 patients with ENKTL treated at our institution with mSMILE from 10/2009-3/2019. Early-stage patients were planned to receive 2 cycles of mSMILE+IMRT, advanced stage 3-4 cycles of mSMILE+/-IMRT. We collected patient characteristics and estimated survival with the Kaplan-Meier method.

**Results:** Patient characteristics were: age median 52y (24-69); female 53%; Asian 25%, other races 75%. Response post mSMILE was 93% (26/28, CR 68%) and response post IMRT was 95% (23/24, CR 87.5%). After a median follow-up of 31 months (range 5-105) 17 patients are alive (61%). Among early-stage patients (IE)/low PINK-E (n=13), overall survival (OS) was 100% at the median follow up, and progression-free survival (PFS) was 92%. However, there were two subsequent events: one death due to relapse and one death from unrelated causes in remission. Intermediate and high-risk stage/PINK-E patients fared similarly, with an OS of 43% and a PFS of 33.3% at the median follow-up. Four pts (14%) had chemotherapy dose reductions, 9 pts (32%) experienced G3-4 non-hematologic toxicity, all pts had hematologic toxicity, for 21/28 (75%) G3-4. Twenty-four pts, (86%) received RT as part of their treatment course. 22/24 received IMRT consolidation post 1-2 mSMILE 16 with receiving 4500 cGy. Of these 22, 2 pts received IMRT consolidation composite with total body irradiation conditioning for allo-transplant to total doses of 3947 cGy. An example of IMRT field design is shown in the figure.

**Discussion:** In 28 patients treated at MSKCC for newly diagnosed ENKTL with mSMILE+/-IMRT, we confirmed the overall high response rate with mSMILE. This is a highly active albeit aggressive approach with good results in patients with early-stage/favorable risk disease for whom the PFS and OS were excellent. However,

outcomes remain inadequate for those with more extensive disease or higher risk factors. For these patients, the recent identification of new agents including pembrolizumab and daratumumab raise the possibility of novel regimens or approaches.

**Keywords:** extranodal lymphomas; L-asparaginase; T-cell lymphoma (TCL).

446

EXTRANODAL NATURAL KILLER (NK)/T-
CELL LYMPHOMA, NASAL TYPE – CASE
REPORT AND REVIEW OF CZECH
LYMPHOMA STUDY GROUP (CLSG)
DATABASE

K. Steinerova¹

P. Jindra¹

D. Lysak¹

M. Karas¹

M. Trneny²

P. Klener²

A. Sykorova³

D. Belada³

A. Janikova⁴

R. Pytlik⁵

V. Prochazka⁶

K. Benesova²

P. Blahovcova²

¹Department of Hematology and Oncology, Charles University Hospital, Pilsen, Czech Republic; ²¹st Department of Internal Medicine–Department of Hematology, First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic; ³⁴th Department of Internal Medicine-Hematology, University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic; ⁴Department of Hematology and Oncology, University Hospital, Brno, Czech Republic; ⁵Department of Clinical Hematology, University Hospital Kralovske Vinohrady and 3rd Faculty of Medicine, Praha, Czech Republic; ⁶Department of Hemato-Oncology, Faculty of Medicine, Olomouc, Czech Republic

**Introduction:** Nasal NK/T-cell lymphomas (ENKL) show a geographic predilection for Asian and South American populations (incidences
with 5.2 and 3%), and are uncommon in other countries (incidences with just 0.3% in North American and European countries). The prognosis for patients (pts) with advanced or refractory ENKL is extremely poor. The role of allogeneic transplantation (alloSCT) has been explored in a few small retrospective studies, which almost exclusively were comprised of Asian patients. Here, we describe the case report of pt with refractory ENKL successfully treated with haploidentical transplantation (haploSCT) and provide the analysis of ENKL in Caucasian pts using the observational database of the Czech Lymphoma Study Group (CLSG).

**Case report:** A 35-year-old woman was referred to our department with 6 years history of autoimmune granulomatosis (repeated biopsy from mouth), last biopsy from the right vestibule diagnosed ENKL. PET CT scan showed involvement of gingiva, face and one mediastinal lymph node. Pt was treated with 4 cycles of chemotherapy (CHOEP), after the initial improvement the progression of ENKL on the tongue was histologically verified. Salvage chemotherapy DHAP was started with subsequent progression after the first cycle. The 3rd line chemotherapy DeViC (2 cycles) was administered only with a partial transient effect and early recurrence of lymphoma infiltration. Radiotherapy of soft facial tissues was performed with complete regression of infiltrates. However early after the radiotherapy 2 new FDG accumulating lesions in spleen were detected. Early haploSCT was performed (donor haploidentical brother, reduced intensity conditioning). 1 year after the haploSCT pt is alive in complete remission of ENKL.

Further we analyzed the group of pts with ENKL from CLSG database. 40 adult (≥18 years) pts with ENKL were reported to the CLSG database between 1999 and 2018. The median age at the time of diagnosis was 52 years (range: 21-86); 62% were male and 74% had ECOG 0-1. Therapy was known for 37 pts; 18 (49%) received only chemotherapy (mostly CHOP and CHOEP), 2 (5%) radiation alone, and 17 (46%) received combined radiation and chemotherapy. 19 pts (52%) responded after the first line treatment; 16 pts (43%) achieved CR and 3 pts (8%) PR, 6 pts. (16%) were not evaluable and 12 pts (32%) had primary progressive disease. 10-years probability of OS of the whole group was 38%, RFS 27%. 7 pts from progressive disease group received second line chemotherapy with subsequent further progression, 1 pt underwent alloSCT and achieved complete remission. Except for the patient after alloSCT all pts died from disease progression.

**Discussion:** alloSCT should be considered for high-risk or advanced-stage patients in remission or relapsed/refractory ENKL. However, reports of alloSCT for ENKL are limited because of the rarity of the disease. GovTrial Number: NCT03199066.

**Keywords:** allogeneic stem cell transplant (alloSCT); extranodal lymphomas; reduced-intensity conditioning regimen (RIC).

**A. Fujimoto**¹ | **F. Ishida**² | **K. Izutsu**³ |

**S. Yamasaki**⁴ | **D. Chihara**⁵ | **J. Suzumiya**¹ |

**T. Mitsui**⁶ | **K. Ohashi**⁷ | **H. Nakazawa**⁸ |

**H. Kobayashi**⁹ | **J. Kanda**¹⁰ | **T. Fukuda**¹¹ |

**Y. Atsuta**¹² | **R. Suzuki**¹

¹Department of Oncology and Hematology, Shimane University Hospital, Izumo, Japan; ²Department of Biomedical Laboratory Sciences, Shinshu University School of Medicine, Matsumoto, Japan; ³Department of Hematology, National Cancer Center Hospital, Tokyo, Japan;

⁴Department of Hematology and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan

⁵Medical Oncology Service, Center for Cancer Research National Cancer Institute, National Institute of Health, MD, United States

⁶Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan; ⁷Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan;

⁸Department of Hematology, Shinshu University School of Medicine, Matsumoto, Japan; ⁹Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan; ¹⁰Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;

¹¹Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan; ¹²Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya University Graduate School of Medicine, Nagoya, Japan

**Introduction:** Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature natural killer cell neoplasm that is closely associated with Epstein-Barr virus. ANKL presents a fulminant clinical course, resulting in a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment, but the long-term outcomes after allo-HSCT remain unclear.

**Methods:** Using the national Japanese transplant registry database, the outcomes of 59 ANKL patients who underwent first allo-HSCT between 1997 and 2016 were analyzed.

**Results:** The median patient age was 37 years (range, 9 to 66), and males accounted for 68%. The median time from diagnosis to allo-HSCT was 3.7 months (range, 1.1 to 13.9). Twenty-nine patients received stem cells from cord blood (CB), 18 received them from peripheral blood (PB) and 12 received them from bone marrow (BM). Two patients had a prior history of autologous HSCT. Twenty-one patients (36%) had complete response (CR), and 7 (12%) had partial response (PR), but 31 (52%) were not responding at the time of allo-HSCT. Forty-four patients received myeloablative conditioning and 15 received non-myeloablative conditioning. Thirty-two patients received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, including 1 with additional post-transplant cyclophosphamide as part of haploidentical HSCT, whereas 26 received cyclosporin-based prophylaxis. The median overall survival (OS) and relapse-free survival were 3.9 months and 2.6 months, respectively. The median cumulative incidences of relapse and non-relapse mortality were 1.5 months and 2.2 months, respectively. The probability of OS was significantly
<figure><img src="image_273.png" /></figure>

higher for patients in CR or PR at allo-HSCT than for those without a response (40.6% vs 16.1% at 5 years after HSCT, P = 0.046). Among the 24 patients with primary induction failure at allo-HSCT, 15 achieved CR after allo-HSCT. The prognosis of these 15 patients was almost equivalent to that of those who received allo-HSCT in CR or PR, as shown in the Figure (P = 0.95). Regarding the stem cell source, the probability of OS was significantly higher for patients who received stem cells from CB than for those who received them from PB or BM (P = 0.04). The time from diagnosis to allo-HSCT was not different based on the stem cell sources (median CB 3.3 months, PB 3.7 months, and BM 4.1 months; P = 0.31). Patients who developed acute GVHD grade 1/2 had a significantly better prognosis than those with grade 3/4 or without GVHD (P < 0.001). At last follow-up, 42 patients (71%) had died. The most common cause of death was primary disease (62%).

**Conclusion:** Although patients with ANKL have a poor prognosis, allo-HSCT can induce stable remission even for patients with primary induction failure at HSCT. CB is a good alternative stem cell source, which enables timely allo-HSCT for this rapidly progressive disease.

**Keywords:** allogeneic stem cell transplant (alloSCT); Epstein-Barr virus (EBV); T-cell lymphoma (TCL).

**Disclosures:** **Ishida, F:** Research Funding: Bristol-Myers Squibb. **Izutsu, K:** Consultant Advisory Role: Eisai, MSD, Takeda, Ono, AstraZeneca, Abbvie, Bayer, Novartis, Chugai, Daiichi Sankyo, Otsuka; Honoraria: Kyowa Hakko Kirin, Eisai, MSD, Takeda, Janssen, Dainippon Sumitomo, Mundipharma, Nihon Mediphysics, Abbvie, Chugai, Zenyaku, Bristol-Myers Squibb, Astellas; Research Funding: HUYA bioscience, MSD, Astellas Amgen, AstraZeneca, Abbvie, Eisai, Ono, Sanofi, ARIAD, Symbio, Zenyaku, Celgene, Solaisia, Takeda, Daiichi Sankyo, Chugai, Novartis, Bayer, Pfizer. **Suzumiya, J:** Honoraria: Chugai-Roche, Celgene, Janssen, Takeda, Bristol-Myers Squibb; Research Funding: Celgene, Kyowa Hakko Kirin, Chugai-Roche, Eisai, Takeda, Celltrion, SymBio, Ono, Astellas. **Mitsui, T:** Research Funding: Astellas Pharma. **Suzuki, R:** Honoraria: Kyowa-kirin Chugai Bristol-Myers Squibb, Eisai MSD Takeda Meiji-Seika Ono-Pharma Novartis.

448
# UPDATED ANALYSIS OF GENETIC SEQUENCING OF NORTH AMERICAN ATLL

**M. Janakiram**¹ | **A. Villaorduna**² | **R. Sica**² |
**N. Kornblum**² | **I. Braunschweig**² | **E. Chung**² |
**U.A. Shah**³ | **Y. Wang**² | **A.K. Verma**² | **H.B. Ye**²

¹HOT, University of Minnesota, Minneapolis, United States; ²Oncology, Albert Einstein College of Medicine, Bronx, United States; ³Oncology, Memorial Sloan Kettering Cancer Center, Bronx, United States

ATLL (Adult T cell Leukemia Lymphoma) is an aggressive leukemia caused by HTLV-1 virus and is inherently resistant to chemotherapy. A recent whole genome/exome sequencing of 81 Japanese ATL cases identified alterations that overlap with the HTLV1 Tax interactome and are highly enriched for T cell receptor-NF-kB signaling, and T cell trafficking (Kataoka, Nagata et al. 2015). We showed that ATL in Caribbean patients carries a poor prognosis, has distinctive clinical and genomic features with more epigenetic mutations and less TCR mutations when compared to the Japanese cohort (Zell, Assal et al. 2016). Here we report the updated results of 35 patients in the Caribbean cohort (Shah U et al, 2018 and additional results).

Targeted exon sequencing was performed on 35 North American ATLL patients and classified by the Shimoyama criteria. 45.7% (n=16) were acute, 42.9% (n=15) were lymphomatous and 11.4% (n=4) were chronic/smoldering ATLL with an average of 4.92 and 3.75 identified mutations per sample in acute and chronic cases respectively. Genes most commonly mutated in North American ATLL were TP53 (8/35, 23%), FAT1 (8/35, 23%), EP300 (7/35, 20%), NOTCH1 (8/35, 23%), APC (5/35, 15%), TBL1XR1 (5/35, 14%). 54% (19/35) of the cases carry mutations in the epigenetic and histone modifying genes, including EP300, TET2, EZH2, MED12, PBRM1, DNMT3A, KMT2A, HIST1H1E, SPEN, IDH1, SMARCB1 and ASXL1. Comparison with the germline profiles demonstrated that the majority of epigenetic and TP53 mutations were somatic in nature while FAT1 alterations originated from the germline. Frequency of TCR pathway mutations was high in the Japanese cohort but was conspicuously low in our cohort (e.g., CARD11 was mutated at 11.4 vs 23.8% in the two cohorts) while tumor suppressor mutations like TP53 were also higher at 23% (vs 13.6% in the Japanese) in our cohort.

In summary, there is a higher rate of epigenetic mutations, lower rate of TCR pathway genes such as CARD11 in our cohort. Some of the differences might be due to the lower percentage of chronic/smoldering cases in our cohort. In the cohort from France, with African and Caribbean patients, 50% of patients had epigenetic mutations, which was considerably higher than the Japanese cohort (22.2%) and similar to our cohort (Marcais et al ASH 2018 abstract 2841). The impact of these epigenetic mutations on the development and clinical characteristics of ATLL merits further investigation and may provide a basis for epigenetic based therapies in ATLL.

**Keywords:** human T-lymphotropic virus (HTLV); molecular genetics; T-cell lymphoma (TCL).

**Disclosures:** JANAKIRAM, M: Honoraria: miRagen, Seattle Genetics.
States; ⁴Hematologic Malignancies, Thomas Jefferson University, Philadelphia, United States

<table><caption>TABLE 1 Patient Characteristics</caption><thead><tr><th>Characteristic</th><th>N=60 (%)</th></tr></thead><tbody><tr><td>Sex</td><td></td></tr><tr><td>Male</td><td>29 (48)</td></tr><tr><td>Female</td><td>31 (52)</td></tr><tr><td>Presenting Cytopenia</td><td></td></tr><tr><td>Neutropenia (ANC &lt;1500/mm³)</td><td>11 (18)</td></tr><tr><td>Anemia (HgB &lt;12 g/dL)</td><td>17 (28)</td></tr><tr><td>Both</td><td>13 (22)</td></tr><tr><td>Neither<sup>+</sup></td><td>15 (25)</td></tr><tr><td>Unknown</td><td>4 (7)</td></tr><tr><td>LGL Count: CD3CD8+ (at Diagnosis)</td><td>N = 52</td></tr><tr><td>&lt; 1500</td><td>25 (48)</td></tr><tr><td>≥ 1500</td><td>27 (52)</td></tr><tr><td>LDH at Diagnosis (190 = U/L Normal)</td><td>N = 50</td></tr><tr><td>≤ 190</td><td>28 (56)</td></tr><tr><td>&gt; 190</td><td>22 (44)</td></tr><tr><td>Splenomegaly</td><td>N=58</td></tr><tr><td>Yes</td><td>16 (27)</td></tr><tr><td>No</td><td>42 (43)</td></tr><tr><td>Associated Autoimmune Disease</td><td></td></tr><tr><td>Rheumatoid Arthritis (RA)</td><td>16 (27)</td></tr><tr><td>Autoimmune other than RA</td><td>6 (10)</td></tr><tr><td>None</td><td>38 (63)</td></tr><tr><td>Additional Hematologic Malignancy*</td><td></td></tr><tr><td>Pure Red Cell Aplasia</td><td>3 (5)</td></tr><tr><td>Myelodysplasia</td><td>2 (3)</td></tr><tr><td>Lymphoma</td><td>5 (8)</td></tr><tr><td>Evolving Myeloma</td><td>1 (2)</td></tr><tr><td>1st Line Treatment</td><td></td></tr><tr><td>None</td><td>11 (18)</td></tr><tr><td>Methotrexate</td><td>30 (52)</td></tr><tr><td>Cyclosporine</td><td>8 (13)</td></tr><tr><td>Other</td><td>10 (17)</td></tr><tr><td>2nd Line Treatment</td><td>N=24</td></tr><tr><td>Cyclophosphamide</td><td>10 (42)</td></tr><tr><td>Methotrexate</td><td>8 (33)</td></tr><tr><td>Cyclosporine</td><td>3 (13)</td></tr><tr><td>Other (Splenectomy, Pentostatin, BNZ-1)</td><td>3 (13)</td></tr><tr><td>3rd Line or Greater Treatment</td><td>N=13</td></tr><tr><td>Alemtuzumab</td><td>3 (23)</td></tr><tr><td>Cyclosporine</td><td>3 (23)</td></tr><tr><td>Other</td><td>7 (54)</td></tr></tbody></table>

**Introduction:** T-LGLL is a rare, incurable disorder characterized by clonal proliferation of CD3+CD8+ T-cells that can result in severe neutropenia, anemia and even death. Given the rarity of this disease, there is limited clinical data describing the course of the disease and prognostic factors for survival to guide treatment approaches.

**Methods:** This study was conducted at the OSU James-CCC with IRB approval. All patients with a diagnosis of T-LGLL at OSU prior to 1 October 2018 were included. T-LGL was defined by 2016 WHO criteria: a monoclonal T-cell receptor and CD3+CD8+ population on flow cytometry of at least 500 cells/mm³. All pathology was reviewed by the investigators. Response rates were determined utilizing the criteria from the ECOG 5998 study. Univariate probabilities of overall survival (OS) were estimated utilizing the Kaplan-Meier method using IBM SPSS v 24.0. The log-rank test was utilized to assess for differences between groups for OS.

**Results:** 60 patients, with median age of 64 years (range 30-87) were included in the analysis (Table). With a median follow-up time of 28 months, OS at 1, 3, 5, and 10 years was 94%, 82%, 72%, and 66%. There was a trend toward improved 5-year OS in patients with rheumatoid arthritis (RA) vs those without (88% vs 66%; p=0.138). Women had improved OS at 4 years when compared to men (87% vs 66%; p=.081), and there was a trend towards worse OS at 3-years for patients with LDH > 190 U/L (72% vs 86%; p=.139). There was no impact of age, cytopenia, lymphocyte count, concomitant hematologic malignancy or autoimmune disease, degree of anemia or neutropenia at diagnosis on OS.

Eighty-percent (48/60) patients received first line treatment; with 63% receiving methotrexate (MTX). Overall response rate (ORR) to frontline MTX was 37%; 3 CR (10%) 8 PR (27%). Of 43 evaluable patients, the ORR to all frontline therapy was 16/43=37% (30% PR, 7% CR). Twenty-four (40%) of patients received a second line treatment. Ten received cyclophosphamide (Cy), with 8/10 having received prior MTX. The ORR for 6 patients with prior MTX treatment who received Cy was 75%. ORR in 24 evaluable patients for all second line therapies was 54% (9 PR, 4 CR). 13 patients received a third line or greater treatment, with the ORR 54%.

**Conclusion:** In this large analysis of patients with T-LGLL, we observed impaired long-term survival, with worse OS in patients with high LDH or male sex. ORR to current agents at any stage of treatment is limited, with ORR around 40-50%, highlighting the need for novel therapeutics in this rare disease.

**Keywords:** T-cell lymphoma (TCL); T-cell receptor (TCR); T-cells.

450
THE COMBINATION OF VENETOCLAX AND IBRUTINIB IS EFFECTIVE IN RELAPSED/REFRACTORY T-PROLYMPHOCYTIC LEUKEMIA AND INFLUENCES BCL-2-FAMILY MEMBER DEPENDENCIES

<footnote>*At any time during T-LGL course; +Noted as a lymphocytosis; or incidental</footnote>
C.F. Kornauth¹ | C. Herbaux² | B. Boidol³ |

C. Guillemette⁴ | M.E. Mayerhöfer⁵ | U. Jäger¹ |

S. Kubicek³ | M.S. Davids² | P.B. Staber¹

¹Department for Internal Medicine I, Clinical Division for Hematology, Vienna, Austria; ²Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, United States; ³Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria; ⁴Cancer Research Center (CRC), Laval University, Quebec, Canada; ⁵Department for Radiology, Medical University Vienna, Vienna, Austria

**Introduction:** T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy with poor response to current treatment strategies associated with short survival. We recently demonstrated single agent activity of venetoclax in relapsed/refractory (r/r) T-PLL. As a next step, we set out to identify combination partners of venetoclax to overcome single-agent resistance mechanisms.

**Methods:** We applied next-generation functional testing of primary T-PLL cells from seven patients in a combinatorial screen to identify combination partners for venetoclax with 14 agents including ibrutinib, idelalisib, 5-azacytidine, 6-mercaptopurine, bendamustine, bortezomib, and cisplatin. Two late stage r/r-PLL patients were treated with the best scoring combination. BH3 profiling was performed on patient samples on treatment, and serum levels of drugs were determined using mass spectrometry.

**Results:** A pairwise combination screen of venetoclax on primary T-PLL cells with candidate small molecule inhibitors revealed synergistic action of venetoclax with ibrutinib, idelalisib, and 5-azacytidine, whereas cisplatin antagonized the effect of venetoclax across all patient samples tested. (Fig 1a) Two patients with T-PLL relapsed after at least two treatment lines including alemtuzumab were treated with the combination of venetoclax and ibrutinib, resulting in significant clinical responses with substantial decreases in leukocytosis, LDH and B2M, as well as substantial clinical improvement (Fig 1b). One patient had to stop treatment due to an infectious complication, and the response of the second patient is still ongoing. BH3 profiling indicated that venetoclax serum levels above 1µg/ml enhanced overall apoptotic priming, and ibrutinib increased cellular dependency on BCL-2, suggesting a complementary effect of the two drugs mechanistically.

**Conclusion:** Our early data suggest the possibility of a benefit to the venetoclax + ibrutinib combination in r/r-T-PLL. Ibrutinib may enhance the sensitivity of T-PLL cells to venetoclax by selectively increased BCL-2 dependency. These results provide the basis for an upcoming clinical trial testing the efficacy of combination venetoclax and ibrutinib in a larger cohort of r/r T-PLL patients.

**Keywords:** apoptosis; BTK inhibitors; T-cell lymphoma (TCL).

**Disclosures:** Davids, M: Consultant Advisory Role: AbbVie, Acerta Pharma, Adaptive Biotechnologies, Astra-Zeneca, Celgene, Genentech, Gilead Sciences, Janssen, MEI Pharma, Merck, Pharmacyclics, Roche,

<figure><img src="image_274.png" /></figure>

<figure><img src="image_275.png" /></figure>
Syros Pharmaceuticals, TG Therapeutics, Verastem; Research Funding: Acerta Pharma, Bristol-Myers Squibb, Genentech, MEI Pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem.

451
ADULT T-CELL LEUKEMIA/LYMPHOMA: EPIDEMIOLOGY, CLINICAL FEATURES AND OUTCOME OF A CARIBBEAN COHORT FROM GUADELOUPE

P. Helias<fnref n="1" /> | W.C. Lafrance<fnref n="1" /> | T. Chalabi² |
O. Hippomene<fnref n="1" /> | D. Clavier<fnref n="1" /> | S. Gaumond<fnref n="3" /> |
M. Berdou⁴ | M. Saliege⁴ | B. Garin² |
M. Laruelle⁵ | J. Deloumeaux⁶ | M. Parrens<fnref n="7" /> |
V. Baccini²

**Introduction:** Adult T-cell Leukemia/Lymphoma (ATLL) is a rare mature T-cell malignancy first described in Japan in 1977. The causative agent of ATLL has been identified as the Human T cell Lymphotropic Virus type 1 (HTLV-1) which is endemic in Japan, Caribbean area, South America and parts of sub-Saharan Africa. ATLL is an unfrequent and subsequently unknown in Europa, in opposite to the French overseas departments of the caribbean area. The aim of this study is to report and describe ATLL in the lesser Antilles at the modern area of zidovudine and interferon treatment.

**Methods:** We identified ATLL patients diagnosed in our institution between 2014 and 2018. Charts were reviewed to report clinicopathologic features, treatment patterns and outcomes. ATLL diagnosis is based for all patients on the presence of a clonal T cells proliferation along with positivity for HTLV-1 serology.

**Results:** Among 309 patients positive for HTLV-1 in the 5 years period, 24 developed an ATLL (7.76%). The median age at presentation is 59 years (27-92). The sex ratio M/F was 11/13. Based on the Shimoyama classification, 14 patients (58,9%) had acute subtype, 9 (37,5%) had lymphomatous and 1 (4,1%) chronic disease. 22/24 had lymphadenopathy or deep tumoral syndrom at diagnosis whereas 2 patients presented splenomegaly. LDH was elevated in 23 patients. Hypercalcemia was present in half of the cases. Lymphocytosis was present in 7 patients and typical flower cells in 14 cases. Circulating lymphocyte phenotyping, performed for 19 patients, showed clonal T-cells in 15 cases. Two third of the available karyotype were complex.

Most of the patients (n=22) received first-line treatment, whereas 2 quickly passed away before initiating any specific medication. As first line, 11 patients were treated by zidovudine and pegylated interferon, 10 patients received a polychemotherapy only or associated with zidovudine and peg-interferon and one received steroid only. Among the 15 patients with relapse or refractory diseases, 6 were able to receive a second line treatment. One patient benefits from haploidentical bone marrow transplantation. Five patients are still alive at last follow-up. Among them, 4 are still treated with interferon and zidovudine. Mean overall survival is 10.1 months. Among the 18 death with available data: 10 were related to ATLL progression and 8 to infections or acute respiratory distress syndrome.

**Conclusion:** We report the first description of ATLL in Guadeloupe island with young patients and dominance of acute and lymphomatous ATLL subtypes. Shimoyama classification requires a very low blood cell count (<1%) for lymphomatous category. Cytologic detection of flower cells needs trained biologists and can be improved by immunophenotyping which might be worthly introduced in this classification. Despite large and early use of zidovudine and interferon, with or without chemotherapy, ATLL remains a very poor prognostic disease. Innovative therapies are still needed.

**Keywords:** human T-lymphotropic virus (HTLV); interferon (INF); T-cell lymphoma (TCL).

452
PUVA AND INTERFERON α2b COMBINED THERAPY FOR PATIENTS WITH MYCOSIS FUNGOIDES: A SEVEN-YEAR RETROSPECTIVE STUDY IN RUSSIA

E.V. Grekova | O.Y. Olisova | K.V. Smirnov

V.A. Rakhmanov Department of Skin and Venereal Diseases, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

**Introduction:** Cutaneous T-Cell Lymphomas (CTCLs) are characterized by proliferation and accumulation of malignant monoclonal T lymphocytes or Natural Killer cells in the skin, which may also sequentially involve lymph nodes, internal organs and bone marrow. There are still only a limited number of controlled studies to support treatment decisions for MF patients with therapy being frequently determined by institutional experience and availability.

The aim of our survey was to investigate the efficacy and tolerability of combined PUVA and IFN-α2b therapy in patients with different stages of MF, refractory to first line treatment with PUVA.

**Methods:** We observed 31 patients with MF. The diagnoses were verified with histological, immunohistochemical methods and molecular analysis. The following combined IFN-α2b - PUVA treatment protocol was used: IFN-α2b was administered at a dose of 3 MU three times weekly. The dose was increased according to patient's tolerance up to

<footnote n="1">¹Hematology and Oncology Department, University Hospital of Guadeloupe, Pointe à Pitre/Abymes, France; ²Hematology Laboratory, University Hospital of Guadeloupe, Pointe à Pitre/Abymes, France;</footnote>

<footnote n="3">³Pathology, University Hospital of Guadeloupe, Pointe à Pitre/Abymes, France; ⁴Pharmacy, University Hospital of Guadeloupe, Pointe à Pitre/Abymes, France; ⁵Medical Oncology, Medical Center of Saint Martin, Saint Martin, France; ⁶General Cancer Registry of Guadeloupe, University Hospital of Guadeloupe, Pointe à Pitre/Abymes, France;</footnote>

<footnote n="7">⁷Pathology, University Hospital of Bordeaux, Pessac, France</footnote>
6 MU three times weekly. For PUVA therapy, 0.8 mg/kg oral 8-methoxypsoralen was given 1.5 hours before UVA radiation, three times a week with gradually increasing dose of 0.5-1.0 J/cm2 in every 2 sessions starting from a dose of 0.5-2 J/cm2 depending on skin phototype. Treatment toxicity was graded according to World Health Organization (WHO) criteria.

**Results:** In terms of the stage of the disease, patients were distributed as follows: IB - 3 (10%), IIA - 7 (23%), IIB - 6 (19%), IIIA - 4 (12%), IIIB - 3 (10%), IVA - 3 (10%), IVB - 5 (16%). The mean total IFN-α2b dose was 275 MU (range 171-576 MU). Conversely, the median PUVA sessions for the entire group of patients was 81 with the median joules/ cm2 being 177.13 (range 127-204 joules/ cm2) and the median combination treatment period being 189 days (range 133-254 days). The overall response rate was 93%, including complete response (CR) (73%) and partial response (PR) (20%). CR was found in 100% stage IIB-IIIA group respect 0% in stage IIIB-IV, P<0.05; the CR rate was in line with the mean CR percentage reported in previous studies (76.5%). Patients with early stage disease had a 2-year progression free survival of 100% vs. 82% for the advanced stage group (P<0.001). In our study, combined treatment showed a 2- and 5-year progression free survival (PFS) of 90% and 43%, respectively; obviously, patients with early stage disease had a superior 2-year PFS respect to the advanced stage group (100% vs 82%) (P < 0.001).

**Conclusion:** IFN-α2b + PUVA combined treatment seemed to be an efficacious therapy option for MF patients refractory to PUVA ± topical corticosteroids, presenting also a convenient tolerability profile, especially in patients with IB-IIB stage. This combined therapy protocol showed to be effective in both early and advanced MF disease stage, even if significantly better outcomes were observed for early stage disease.

**Keywords:** interferon (INF); mycosis fungoides (MF); phototherapy.

453
SURVIVAL AMONG A PATIENT COHORT
OF RELAPSED/REFRACTORY MYCOSIS
FUNGOIDES IN FRANCE, GERMANY, ITALY,
SPAIN AND THE UNITED KINGDOM

M. Bagot<fnref n="1" /> | T. Illidge² | N.A. Waser<fnref n="3" /> | M. He<fnref n="3" /> |

T. Li<fnref n="3" /> | R. Sambrook<fnref n="3" /> | A. Zomas⁴ |

N. Bent-Ennakhil⁴ | M. Little⁵ | P. Ortiz⁶ |

N. Pimpinelli⁷ | M. Dalal⁵ | C. Assaf⁸

Florence, Italy; ⁸Dermatology and Venerology, HELIOS Klinikum Krefeld, Krefeld, Germany

**Introduction:** Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL) wherein those with advanced stage have a poor prognosis, severe skin manifestations, blood and/or lymph node involvement, and compromised survival. The aim of this study was to describe patient clinical characteristics, management and survival in MF patients who were refractory or had relapsed after a first systemic therapy across 5 European countries.

**Methods:** A retrospective multicenter chart review study was conducted at 19 European sites. Patient data were pseudonymized following both central & local Ethics Committees approval. Inclusion criteria allowed patients to enrol if they had a first diagnosis of MF and proved to be relapsed/refractory (R/R) prior to 1-Jan-2016 after a first course of systemic therapy. Overall survival (OS) was estimated from the date of R/R (defined here as index date) using Kaplan-Meier estimates.

**Results:** This analysis included 69 R/R MF patients with a median follow-up of 3.9 (range: 0.1-16.9) years from the index date. The median age at index date was 60.0 (range: 22-84) years. After R/R 68 (98.6%) patients received further treatment including systemic therapies in routine practice (91.2%), allogeneic stem-cell transplant (1.5%) and treatment within a clinical trial (7.3%). At treatment initiation following R/R, the majority of patients had advanced stage, i.e. IIB-IVB (64.3%) as per the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer. At index date 45 patients (66.2%) had one or more new lymphoma lesions, mostly associated with MF subtype but other new subtypes were observed in a small number of patients. The presence of large cell transformation was detected in 12.5% at index date. In total 72.1% of patients became refractory or relapsed again at end of therapy in R/R, with a median time to next R/R of 15.8 (range: 0.6-174.6) months. In total, 27 deaths (39.1%) were observed during the study, with a median age at death of 65 (range: 50-85) years. The majority of patients (74.1%) died from CTCL, CTCL complications, or toxicity from treatment of CTCL. The estimated median OS was 11.5 years (95% CI: 6.5 – not reached [NR]) from time of R/R in this MF population (Figure). There were some differences in trends in OS according to treatment received for R/R, with single and combination chemotherapies having an estimated median OS of 6.5 years (95% CI: 2.25 – NR) compared to NR (95% CI: 12.1 – NR) for the other systemic therapies (i.e. retinoids, methotrexate, interferon and photopheresis).

**Conclusions:** This analysis from an observational study in treated R/R MF who previously received one systemic therapy estimates median OS at 12 years. The high rate of relapse suggests that the clinical burden of R/R MF is significant in Europe, and in this context recently approved targeted therapies have the potential of improving outcomes

**Keywords:** chemotherapy; cutaneous T-cell lymphoma (CTCL); mycosis fungoides (MF).

**Disclosures:** Bagot, M: Research Funding: Takeda Millenium. Illidge, T: Research Funding: Millenium.

<footnote n="1">¹Polyclinique de Dermatologie, Hopital Saint-Louis, Paris, France; ²The Christie Trust, University of Manchester, Manchester, United Kingdom;</footnote>

<footnote n="3">³Real World Evidence Strategy and Analytics (RWESA), ICON plc, Vancouver, Canada; ⁴EUCAN Medical Affairs, Takeda Pharmaceutical International AG, Zurich, Switzerland; ⁵Millenium Pharmaceuticals Inc, A wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, United States; ⁶Facultad de Medicina, Hospital Universitario 12 de Octubre, Madrid, Spain; ⁷U.O. Ematologia, Hospital P. Palagi,</footnote>
<figure><img src="image_276.png" /><figcaption>Figure: Kaplan Meier curve for OS from time of R/R</figcaption></figure>

Legend: Grey area represents the 95% CI. + represents censored data

HODGKIN LYMPHOMAS

454

TREATMENT PATTERNS, CLINICAL
OUTCOMES, AND BIOMARKER
EVALUATION IN CLASSICAL HODGKIN
LYMPHOMA: A PROSPECTIVE
OBSERVATIONAL STUDY IN US
ONCOLOGY PRACTICES

J. Svoboda<fnref n="1" /> | P. Armand² | P. Porcu³ |
J.M. Burke⁴ | D. Stevens⁵ | M. Moezi⁶ | M. Bajaj⁷ |
E.H. Cull⁸ | Y. Wan⁹ | C. Duan¹⁰ | A. Forslund¹¹ |
S. Gajavelli¹² | C. Yasenchak¹³

Princeton, United States; ¹⁰Moffitt Cancer Center, Bristol-Myers Squibb, Princeton, United States; ¹¹Precision Medicine and Translational Research in Oncology, Bristol-Myers Squibb, Princeton, United States; ¹²Bristol-Myers Squibb, Princeton, United States; ¹³Medical Oncology and Hematology, Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, United States

**Introduction:** Classical Hodgkin lymphoma (cHL) is highly curable with frontline multi-agent chemotherapy (CTx) +/- radiotherapy, but standard-of-care treatment (Tx) for relapsed/refractory (R/R) cHL fails in ~50% of patients (pts). The programmed death-1 (PD-1) inhibitors nivolumab and pembrolizumab have expanded Tx options in cHL. Thus, it would be beneficial to understand current Tx patterns and identify pts who are likely to be refractory to conventional Tx early in the disease course.

**Methods:** This is an ongoing, prospective, observational study (NCT02856646) at ~80 US oncology practices with a target enrollment of 500 pts and a planned follow-up of ≤ 5 y. Eligible pts were ≥ 18 y with histologically confirmed cHL, beginning any line of Tx. Index therapy was defined as Tx received at or within 2 wk of enrollment. Blood and tissue samples were collected for biomarker analysis, including PD-1 ligand (PD-L1) expression on Hodgkin Reed-Sternberg (HRS) cells/tumor microenvironment (TME), and quantification of CD68+ tumor-associated macrophages.

**Results:** At data cutoff, 266 pts were enrolled; median (range) age was 38 (18-90) y, 56% were male, and 82% white. In all, 260 (98%) pts received CTx, 5 (2%) immunotherapy (IO), and 1 stem cell transplantation as index Tx. 216 (81%) pts were Tx naive at study enrollment and

<footnote n="1">¹Lymphoma Program, University of Pennsylvania, Philadelphia, United States; ²Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States; ³Division of Medical Oncology and Hematopoietic Stem Cell Transplantation, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, United States; ⁴Medical Oncology / Hematology, Rocky Mountain Cancer Centers, Aurora, United States; ⁵Hematology and Medical Oncology, Norton Cancer Institute, Louisville, United States; ⁶Medical Oncology, Hematology and Internal Medicine, Cancer Specialists of North Florida, Fleming Island, United States; ⁷Medical Oncology, Illinois Cancer Care, Peoria, United States; ⁸Hematology/Oncology, Greenville Health System, Greenville, United States; ⁹Center for Observational Research, Bristol-Myers Squibb,</footnote>
<figure><img src="image_277.png" /><figcaption>Figure. Percentage of PD-L1+ HRS cells (A) and percentage of CD68+ cells (B) by disease stage among pts receiving frontline Tx</figcaption></figure>

received frontline Tx as index Tx; 50 (19%) pts had R/R disease. Frontline index Tx consisted of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 89% of pts; of evaluable pts, complete response (CR) was achieved in 70% and partial response (PR) in 16%. Among pts with R/R cHL, the most common index CTx were ICE (ifosfamide, carboplatin, etoposide; n = 19, 45%) and brentuximab vedotin (n = 15, 36%), and the most common index immunotherapy was nivolumab (n = 4, 80%); of evaluable pts, CR was achieved in 57% and PR in 14%. In total, 15 pts (6%) received IO during the study (as index or non-index Tx). Tx-related adverse events occurred in 83% of all pts, including 5 deaths. Analysis of toxicity patterns is ongoing. Currently, 196 pts have data available for biomarker analyses. Among frontline-treated pts (n = 158), increased CD68+ tumor-associated macrophages in TME correlated with advanced-stage disease (P < 0.001); increased PD-L1 expression in HRS cells showed a trend correlating with advanced-stage disease (Figure). Pts with CR after frontline Tx tended to have fewer CD68+ cells in the TME, but no difference in the percentage of PD-L1+ HRS cells or tumor-associated immune cells. Enrollment is ongoing and additional outcomes-biomarker association analyses will be presented.

**Conclusions:** Initial data from this study suggest that up to 30% of pts treated with conventional frontline CTx regimens did not achieve

CR. Defining predictors of outcomes to conventional Tx and immunotherapies using biomarkers may ultimately result in developing more effective and less toxic Tx algorithms.

**Keywords:** chemotherapy; Hodgkin lymphoma (HL); nivolumab.

**Disclosures:** Svoboda, J: Consultant Advisory Role: Astra-Zeneca, Bristol-Myers Squibb, Kite, Kyowa, Seattle Genetics; Research Funding: Bristol-Myers Squibb, Celgene, Incyte, Merck, Novartis, Pharmacyclics, Seattle Genetics, TG. Armand, P: Consultant Advisory Role: Adaptive, Affimed, Bristol-Myers Squibb, Infinity, Merck, Pfizer; Research Funding: Adaptive, Affimed, Bristol-Myers Squibb, Merck, Otsuka, Roche, Sigma Tau, Tensha. Porcu, P: Consultant Advisory Role: Innate Pharma, Viracta; Honoraria: Kiowa, Spectrum; Research Funding: ADCT therapeutics, BeiGene, Incyte, Innate Pharma, Kura, Miragen, Pfizer, Seattle Genetics, Viracta. Burke, J: Consultant Advisory Role: AbbVie, Astra-Zeneca, Bayer, Celgene, Genentech, Gilead, Juno, Seattle Genetics, Tempus Labs. Stevens, D: Other Remuneration: Membership on Board of Directors/advisory committee: Bayer. Cull, E: Other Remuneration: Speaker: Celgene. Wan, Y: Employment Leadership Position: Bristol-Myers Squibb. Duan, C: Employment Leadership Position: Bristol-Myers Squibb. Forslund, A: Employment Leadership Position: Bristol-Myers Squibb. Gajavelli, S: Employment Leadership Position: Bristol-Myers Squibb. Yasenchak, C: Consultant Advisory Role: Bristol-Myers Squibb, Seattle Genetics.

455

PRELIMINARY RESULTS OF A QUALITY
CONTROL STUDY ON INVOLVED NODE
RADIOTHERAPY IN THE EORTC/LYSA/FIL
H10 TRIAL ON STAGES I/II HODGKIN
LYMPHOMA

B.M. Aleman<fnref n="1" /> | U. Ricardi² | R.W. van der Maazen³ |
P. Meijnders⁴ | M. Beijert⁵ | A. Boros⁶ | F. Izar⁷ |
C.P. Janus⁸ | M. Levis² | V. Martin⁶ | L. Specht⁹ |
C. Corning¹⁰ | E. Clementel¹⁰ | C. Fortpied¹⁰ |
J.M. Raemaekers¹¹ | M.P. Andre¹² | M. Federico¹³ |
T. Girinsky⁶

<footnote n="1">¹Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands; ²Oncology, University of Turin, Turin, Italy; ³Radiotherapy, Radboud University Medical Centre, Nijmegen, Netherlands;
⁴Radiotherapy, GZA Ziekenhuizen campus Sint-Augustinus, Wilrijk, Belgium; ⁵Radiotherapy, University Medical Center Groningen, Groningen, Netherlands; ⁶Radiotherapy, Institut Gustave Roussy, Villejuif, France;
⁷Radiotherapy, Institut universitaire du cancer de Toulouse, Toulouse, France; ⁸Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, Netherlands; ⁹Oncology, Rigshospitalet, Copenhagen, Denmark; ¹⁰Head Quarters, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; ¹¹Internal Medicine, Rijnstate Hospital, Arnhem, Netherlands; ¹²Hematology, CHU UCL Mont-Godinne-Dinant, Yvoir,</footnote>
Belgium; ¹³Oncology, University of Modena and Reggio Emilia, Modena, Italy

**Introduction:** Recently, the final results of EORTC/LYSA/FIL H10 trial on early Positron Emission Tomography (PET) response-adapted treatment in stage I and II Hodgkin Lymphoma were published. In this trial a new radiotherapy concept was introduced: Involved Node Radiotherapy (INRT). The aim of the current study was to evaluate the quality of INRT in a large multicenter trial in a representative sample of patients.

**Methods:** Approximately 70% of 1950 patients enrolled in H10 were treated with INRT. The aim of this retrospective and descriptive study was to evaluate INRT in a representative sample (~10% of all irradiated patients). To obtain a representative sample, sampling was stratified by study group, year of treatment, size of treatment center, treatment arm and it was done proportional to the size of the strata. Because of the retrospective data collection difficulties with retrieval of the data was anticipated for 1/3 of the patients. The sample was completed with all patients with known recurrences to enable future evaluation of pattern of relapse in relation to the field. A feasibility questionnaire was mailed to centers from which cases were sampled.

The VODCA (Visualisation and Organisation of Data for Cancer Analysis) software, was used to perform the quality control. Most important items that were scored for each case were radiotherapy principle, delineation and coverage of the target volume and applied technique and -dose. Each case was reviewed by 2 reviewers and in case of disagreement an adjudicator was invited to review the case, in order to come to a conclusion.

**Results:** The sample consisted of 219 patients. The feasibility questionnaire showed that centers indicated that uploading the data would be possible for 134 cases. Data collection was, however, hampered by changes in radiology and treatment planning systems during the running period of the trial, significantly more than anticipated. Currently, data were retrieved for 52 patients. Preliminary review results are available for 34 patients. All evaluated patients were treated according to the INRT principle. Approximately 80% of cases were treated according to the protocol. Major deviations were mostly caused by definite or likely misses in target volume delineation.

**Conclusions:** The preliminary results of the current analysis show that principle of INRT was applied to all patients evaluated. Approximately 80% of the patients were treated according to the protocol, which is in line with results from other study groups. In future trials, either prospective quality assurance of radiotherapy will be done or data will be collected prospectively to enable quality control. The preliminary results should be interpreted with caution because of the number of patients evaluated and because of the potential bias as the currently available data may not be representative for all patients irradiated in the H10 trial.

**Keywords:** Hodgkin lymphoma (HL).

456
CLINICAL OUTCOMES ASSOCIATED WITH
THE TREATMENT OF NEWLY DIAGNOSED
STAGE IV CLASSICAL HODGKIN
LYMPHOMA IN PRACTICE SETTINGS IN
FRANCE, GERMANY AND THE UNITED
KINGDOM

M.R. Dalal¹ | M.U. Hentrich² |

A. Stamatoullas-Bastard³ | E.A. Zagadailov¹ |

A. Gautam¹ | N.A. Way⁴ | M. Cambron-Mellott⁴ |

T.M. Illidge⁵

¹Global Outcomes Research & Epidemiology (Oncology), Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA, Cambridge, United States; ²Rotkreuzklinikum Munich, Munich, Germany; ³Henri Becquerel Center, Rouen, France; ⁴Health Outcomes Practice, Kantar Health, San Mateo, United States; ⁵University of Manchester, Christie Hospital, Manchester, United Kingdom

**Introduction:** Classical Hodgkin lymphoma (cHL) is a hematologic malignancy with poor prognosis for advanced-stage patients who do not respond well to first line (1L) therapy. 1L treatment patterns for cHL are well-known. However, clinical outcomes associated with 1L treatments in a community setting have not been routinely assessed. This study examines clinical outcomes associated with commonly used 1L systemic regimens used to treat Stage IV cHL in France (FRA), Germany (DE), and the United Kingdom (UK) in a community setting.

**Methods:** Hematologists and oncologists (N=47) from FRA, DE, and the UK retrospectively identified patients diagnosed with Stage IV cHL and treated with 1L systemic therapy: doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); doxorubicin, vinblastine, and dacarbazine (AVD); dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP<sub>escalated</sub>); BEACOPP. Descriptive statistics examined patient demographics and 1L systemic regimens. Bivariate analyses (chi-square) compared second line (2L) treatment patterns by 1L systemic regimen. Unadjusted progression-free survival (PFS) was assessed with Kaplan Meier curves and PFS by 1L systemic regimen was compared with a log-rank test. Disease progression was defined as the occurrence of progression, relapse, 2L treatment, or death.

**Results:** Patients in 1L (N=78) were administered ABVD (57.7%), AVD (10.3%), BEACOPP<sub>escalated</sub> (24.4%), or BEACOPP (7.6%). Mean (SD) age at initial diagnosis for the aggregate patient sample was 49.5 (16.1) years, which was mostly male (71.8%) and distributed across FRA (30.8%), DE (26.9%), and the UK (42.3%). Outcomes and 2L treatment patterns are presented in **Table 1**. Median follow-up was 25.5 months (range: 14.0-80.3 months). Unadjusted PFS by 1L systemic regimen is presented in **Figure 1**. Median (95% CI) PFS was 32 months (16-43 months) for 1L ABVD patients, 13 months (0-not
<table><caption>**TABLE 1** 2L treatment patterns and clinical outcomes by 1L systemic regimen</caption><thead><tr><th rowspan="2"></th><th colspan="5">1L Systemic Regimen</th></tr><tr><th>Aggregate (N=78)</th><th>ABVD (N=45)</th><th>AVD (N=8)</th><th>BEACOPP (N=6)</th><th>BEACOPP escalated (N=19)</th></tr></thead><tbody><tr><td colspan="6"><strong>Median (95% CI) Unadjusted PFS</strong></td></tr><tr><td>12-Month PFS</td><td>69.2%<br>(59.0 - 79.5)</td><td>73.3%<br>(60.4 - 86.2)</td><td>50.0%<br>(15.3 - 84.7)</td><td>66.7%<br>(28.9 - 100)</td><td>68.4%<br>(47.5 - 89.3)</td></tr><tr><td>24-month PFS</td><td>52.4%<br>(40.3 - 64.4)</td><td>58.4%<br>(42.6 - 74.2)</td><td>16.7%<br>(0.0 - 45.7)</td><td>44.4%<br>(0.9 - 88.0)</td><td>54.7%<br>(30.9 - 78.6)</td></tr><tr><td colspan="6"><strong>2L Treatment Modality</strong></td></tr><tr><td>Systemic therapy only</td><td>24.4%</td><td>28.9%</td><td>25.0%</td><td>16.7%</td><td>15.8%</td></tr><tr><td>ASCT only</td><td>0.0%</td><td>0.0%</td><td>0.0%</td><td>0.0%</td><td>0.0%</td></tr><tr><td>Radiation therapy only</td><td>1.3%</td><td>2.2%</td><td>0.0%</td><td>0.0%</td><td>0.0%</td></tr><tr><td>Radiation therapy only as consolidation for 1L</td><td>1.3%</td><td>0.0%</td><td>0.0%</td><td>0.0%</td><td>5.3%</td></tr><tr><td>Radiation and systemic therapy</td><td>5.1%</td><td>0.0%</td><td>37.5%</td><td>16.7%</td><td>0.0%</td></tr><tr><td>ASCT and systemic therapy</td><td>7.7%</td><td>6.7%</td><td>0.0%</td><td>16.7%</td><td>10.5%</td></tr><tr><td>Radiation, ASCT, and systemic therapy</td><td>1.3%</td><td>0.0%</td><td>0.0%</td><td>16.7%</td><td>0.0%</td></tr><tr><td>No 2L treatment</td><td>58.9%</td><td>62.2%</td><td>37.5%</td><td>33.2%</td><td>68.4%</td></tr></tbody></table>

Note. No patients were deceased at the time these data were collected. 2L treatment modality differed by 1L systemic regimen in chi-square test, p=0.001. PFS: progression-free survival; CI: confidence interval; 1L: first line therapy; 2L: second line therapy; ASCT stem cell transplant; ABVD: doxorubicin, bleomycin, vinblastine, and dacarbazine; AVD: doxorubicin, vinblastine, and dacarbazine; BEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

estimable) for 1L AVD patients, not estimable for 1L BEACOPP, escalated patients, and 17 months (7-37 months) for 1L BEACOPP patients.

**Conclusions:** These findings demonstrate that treatment outcomes in the clinical practice setting with commonly used treatment regimens may be different than those observed in clinical trials. These findings underscore the unmet medical need in patients with cHL and the importance of novel treatment regimens.

**Keywords:** chemotherapy; classical Hodgkin lymphoma (cHL).

**Disclosures:** Dalal, M: Employment Leadership Position: This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Mehul Dalal is an employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Hentrich, M: Consultant Advisory Role: This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Marcus Hentrich received a consultancy fee for medical expertise on this project from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Stamatoullas-Bastard, A: Consultant Advisory Role: This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Aspasia Stamatoullas-Bastard received a consultancy fee for medical expertise on this project from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Zagadailov, E: Employment Leadership Position: This study was funded by Millennium Pharmaceuticals, Inc., a

wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Erin Zagadailov is an employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Gautam, A: Employment Leadership Position: This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Ashish Gautam is an employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Way, N: Research Funding: This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Nate Way is an employee of Kantar Health, who received funding to conduct this study from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Cambron-Mellott, M: Research Funding: This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. M. Janelle Cambron-Mellott is an employee of Kantar Health, who received funding to conduct this study from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Illidge, T: Consultant Advisory Role: This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA. Timothy Illidge received a consultancy fee for medical expertise on this project from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
<caption>Figure 1. Unadjusted PFS by 1L systemic regimen</caption>

Product-limit Survival Estimate

<figure><img src="image_278.png" /></figure>

Note: There is no significant difference of Kaplan-Meier survival time among 1L therapy groups. Log-rank p=0.138. PFS: progression-free survival; 1L: first line therapy; ABVD: doxorubicin, bleomycin, vinblastine, and dacarbazine; AVD: doxorubicin, vinblastine, and dacarbazine; BEACOPP: dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone; BEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

457

MODIFICATION OF ESCALATED BEACOPP WITH DACARBAZINE / PROCARBAZINE SUBSTITUTION REDUCES RED CELL TRANSFUSION REQUIREMENTS AND MAY SHORTEN TIME TO MENSTRUAL PERIOD RECOVERY

G. Follows<fnref n="1" /> | A. Santarsieri<fnref n="1" /> | K. Sturgess<fnref n="1" /> |

T. Menne² | W. Osborne² | T. Creasey² |

K.M. Ardeshna³ | S. Behan<fnref n="1" /> | S. Booth⁴ |

G. Collins⁵ | K. Cwynarski³ | S. Iyengar⁶ |

S. Jones⁷ | N. Martinez-Calle⁸ | P. McKay⁹ |

S.K. Nagumantry¹⁰ | D. O'Mahony¹¹ | J.F. Rudge¹² |

N. Shah¹³ | G. Stafford<fnref n="1" /> | A. Sternberg¹⁴ |

B. Uttenthal<fnref n="1" /> | A. McMillan⁸

Foundation Trust, Reading, United Kingdom; ⁵Haematology, Oxford University Hospitals NHSFT, Oxford, United Kingdom; ⁶Haematology, The Royal Marsden, London, United Kingdom; ⁷Haematology, Sherwood Forest Hospitals, Sutton in Ashfield, United Kingdom; ⁸Haematology, Nottingham University Hospital NHS Trust, Nottingham, United Kingdom; ⁹Haematology, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; ¹⁰Haematology, Peterborough City Hospital, Peterborough, United Kingdom; ¹¹Haematology, Cork University Hospital, Wilton, Republic of Ireland; ¹²Department of Earth Sciences, University of Cambridge., Cambridge, United Kingdom; ¹³Haematology, Norfolk and Norwich University Hospitals, Norwich, United Kingdom; ¹⁴Haematology, Great Western Hospital NHS Foundation Trust, Swindon, United Kingdom

**Introduction:** It is increasingly common practice to modify escalated BEACOPP (eBPP) by removing oral procarbazine and replacing with intravenous dacarbazine (250mg/m2 D2-3), hoping to reduce haematopoietic stem cell and gonadal toxicity. However, published data on the so-called 'escalated BEACOPDac (eBPDac)' regimen are limited.

**Methods:** We collected retrospective data from 14 UK and Ireland centres that offer this protocol for first line advanced stage Hodgkin

<footnote n="1">¹Haematology, Cambridge University Hospitals NHSFT, Cambridge, United Kingdom; ²Haematology, Freeman Hospital, Newcastle upon Tyne, United Kingdom; ³Haematology, University College London Hospital, London, United Kingdom; ⁴Haematology, Royal Berkshire NHS</footnote>
Lymphoma, and compared outcomes with matched patients treated
with eBPP at 4 UK centres.

**Results:** From 2009, 103 patients were managed first line with either eBPP (n=51) or eBPDac (n=52) with median follow-up 37 months for eBPP and 10.4 months for eBPDac patients. Patients were well matched with no significant differences in age (median: 25), sex, stage (stage 3/4: 82%) and international prognostic score (IPS3+:71%).

More patients treated with eBPDac received only 4 cycles of treat-
ment (54% vs 10%; p=0.0007) reflecting recent HD18 trial data
(1). In total, 74% patients achieved iPET Deauville score 2 or
3 and 98% patients achieved PET negative remission by end of
treatment. Of eBPDac patients, 78% achieved iPET Deauville 2 or
3 which was statistically similar to the eBPP cohort (68%; p=0.344)
and matched the 76% iPET D2/3 reported in HD18 (1). Of
103 patients, 102 are alive and 99 continue in first remission. Two
eBPP patients have relapsed at 13 and 41 months. One eBPDac
patient had primary refractory disease and one eBPDac patient
died with bowel perforation.

Toxicity was compared over the first 4 cycles. There was no differ-
ence in day 8 ALT between the two regimens although the mean day
8 neutrophil count was lower in eBPDac than eBPP patients (1.82 vs
2.35; p=0.056; G-CSF given day 9). There was a trend to fewer non-
elective days of in-patient care for eBPDac compared with eBPP
(mean: 2.8 vs 6.06; p=0.13), and eBPDac patients received fewer red
cell transfusions during cycles 1 to 4 compared with eBPP patients
(Mean 2.06 units vs 4.42 units; p=0.0009). Women aged < 35 with >
6 months post chemotherapy follow-up had a similar rate of return of
menstrual cycles (eBPP: 20/21; eBPDac: 11/12), although eBPDac
patients appeared to restart menstruation earlier post chemotherapy
completion (mean: 3.91 months vs 8.65 months, p=0.0002). However,
this could also reflect the higher mean chemotherapy cycle number
completed by the eBPP women (5.86 vs 4.67; p=0.0005). The use of
monthly Goserelin to suppress ovulation varied between centres.

**Conclusions:** Accepting the limitations of a retrospective study, we suggest that substituting dacarbazine for procarbazine is unlikely to compromise the efficacy of eBPP and may have some toxicity benefits. As it is highly unlikely that this single drug substitution will ever be tested in a prospective trial, publishing real-world data from eBPDac patients is important.

References

1. Borchmann P et al. Lancet. 2018;390:2790-2802

Keywords: BEACOPP; dacarbazine; Hodgkin lymphoma (HL).

**Disclosures:** Follows, **G:** Consultant Advisory Role: BMS, Takeda, Abbvie, Roche, Janssen, Celgene. Osborne, **W:** Consultant Advisory Role: Roche, Takeda, Servier, Gilead, MSD; Honoraria: Roche, Takeda, Pfizer; Other Remuneration: Novartis. Ardeshna, **K:** Consultant Advisory Role: Takeda, Roche, Celgene, ADC therapeutics. McKay, **P:** Consultant Advisory Role: BMS, Takeda, Roche, Janssen, Celgene; Other Remuneration: Lecture fees, support to attend conferences: Takeda, Janssen, Abvie, Gilead. Nagumantry, **S:** Honoraria: Abbvie, Takeda; Other Remuneration: Lecturing: Alexion, Takeda. Shah, **N:** Consultant Advisory Role: Abbvie, Janssen. Uttenthal, **B:** Honoraria: Roche, Takeda, Jazz.

UPDATE
SAFETY AND
EFFICACY
RESULTS OF «HLMoscow 1-3» STUDY FOR
THE 147 UNTREATED PATIENTS WITH
ADVANCED CLASSICAL HODGKIN
LYMPHOMA

G. Tumyan¹ | M. Kichigina¹ | E. Paramonova¹ |

E. Medvedovskaya¹ | O. Trofimova¹ | Y. Ryabuhina¹ |

E. Demina² | P. Zeynalova¹ | O. Kolomeytsev¹

¹Hematology, N.N. Blokhin National Cancer Research Center, Moscow,
Russian Federation; ²Hematology, National Medical and Surgical Center
named after N.I. Pirogov, Moscow, Moscow, Russian Federation

**Introduction:** Standard of care advanced stages classical Hodgkin lym-
phoma (cHL) remains a problem to the discussion over the past
decades. The ABVD is the well tolerant regimen but causes prolonged
remissions in approximately 70% of patients. The BEACOPP is effec-
tive in more than 85% of patients (pts) but associated with a high fre-
quency of early and late adverse events and toxicity. In order to
reduce the long-term effects of treatment, we initiated a protocol
«HLMoscow 1-3» based on 8 cycles of the BEACOPP-14. We omitted
bleomycin because of pulmonary toxicity, increased the dose of doxo-
rubicin to 50 mg\m2 and reduced the number of cycles from 8 to 6.

**Aims:** The purpose of our study was to achieve the highest cure rate with the least reduce the early and late toxicity. We aimed to assess the value of early-interim fluorodeoxyglucose (FDG)-PET scan after two cycles of EA(50)COPP-14 as a predictor of treatment outcome in cHL.

**Methods:** In 2009-2017, 147 pts with advanced stages cHL received treatment in the N.N. Blokhin Cancer Research Center under the protocol «HLMoscow 1-3»: 6 cycles of EA(50)COPP-14 + radiation therapy (RT) for residual mass > 2.5 cm. The median age was 28 years (17-50), 57% were female, B-symptoms were revealed in 69 pts (47%). Consolidation radiotherapy was given to 79 (54%) pts. Interim FDG-PET after 2 cycles (PET2) was performed in 87 (59%) pts. Interim PET images were scored according to the 5-point «Deauville score». Scores ≤3 on the PET2 were considered as negative and scores 4-5 were considered as positive.

**Results:** The median follow-up was 36 months. The efficacy of the protocol was high, estimated 4-year progression-free survival (PFS) was 86 ±4%, overall survival (OS) – 95 ±2,6%. More than 90% of pts received 6 cycles EA(50)COPP-14 without dose reduction. The most frequent advance events III-IV grades were neutropenia (88%), anemia (24%), infection (27,4%), but thrombocytopenia was rare (3,8%). The second tumors were diagnosed in 3 (2,04%) pts. Complete metabolic response (CMR) after 2 cycles had 74 pts (85%), PET2-positive were 13 (15%). CMR is a powerful prognostic and predictor factor for the favorable outcome of pts with cHL: 4-year PFS was 95 ± 2.5% in PET2-negative and 67 ± 17.1% in PET2-positive patients (p = 0.03).
**Conclusions:** The intensive EACOPP-14±RT program showed durable and early response with expected and slight toxicity for pts with advanced stage cHL. Interim FDG-PET is a strong and independent predictor of PFS in cHL and may help risk-adapted treatment strategies by selecting pts for less intensive treatment (omitted radiotherapy for PET2-negative pts)

**Keywords:** BEACOPP; classical Hodgkin lymphoma (cHL).

459
POOLED RESULTS OF THREE ANNUAL
COHORTS FROM AN OBSERVATIONAL
PROSPECTIVE STUDY DESCRIBING
BRENTUXIMAB VEDOTIN USE IN ROUTINE
PRACTICE IN FRANCE FOR HODGKIN
LYMPHOMA: INTERIM ANALYSIS

D. Sibon¹ | P. Quittet² | C. Borel³ |

A. Stamatoullas⁴ | P. Franchi-Rezgui⁵ |

H. Ghesquieres⁶ | R. Dulery⁷ | O. Benbrahim⁸ |

M. Hammoud⁹ | E. Durot¹⁰ | S. De Guibert¹¹ |

C. Coulibaly¹² | O. Casasnovas¹³ | R. Bouabdallah¹⁴ |

P. Brice¹⁵

¹Haematology, Hôpital Necker, Paris, France; ²Haematology, CHU Montpellier-Hop. ST Eloi, Montpellier, France; ³Haematology, IUCT-Oncopole, Toulouse, France; ⁴Haematology, Centre Henri Becquerel, Rouen, France; ⁵Haematology, Hopital Cochin, Paris, France;

⁶Haematology, Centre Hospitalier Lyon Sud, Pierre Bénite, France;

⁷Haematology, Hopital Saint Antoine, Paris, France; ⁸Haematology, CHR Orleans, Orleans, France; ⁹Haematology, Hopital Henri Mondor, Créteil, France; ¹⁰Haematology, Hopital Robert Debre, Reims, France;

¹¹Haematology, CHU Pontchaillou, Rennes, France; ¹²Oncology, Medical department, La Defense, France; ¹³Haematology, CHU de Dijon, Dijon, France; ¹⁴Haematology, IPC, Marseille, France; ¹⁵Haematology, Hopital St Louis, Paris, France

**Introduction:** Use of brentuximab vedotin (BV) in clinical practice has not been widely described as in clinical trial.

**Methods:** A national observational prospective study designed to evaluate the use of brentuximab vedotin (BV) for the treatment of Hodgkin lymphoma (HL) in routine practice. Patients receiving BV are registered in annual independent cohorts since 2015 and until 2018 at participating centers. We report here the pooled results of the 2015, 2016 and 2017 cohorts. The primary objective was to describe the use of BV therapy outside of clinical trials; Secondary objectives were to report response rate according to Cheson 2007, survival and safety.

**Results:** From January 2015 to December 2017, 45 sites registered 405 patients of which 396 were evaluable. 265 patients (67%) have been treated for HL, 127 (32%) for non-Hodgkin lymphoma and 4 for others. HL Patients had been diagnosed at a median of 1 year before BV initiation. They received at any time and modalities chemotherapy for 258 patients (97%), radiotherapy in 58 patients (22%), monoclonal

antibodies in 16 patients (6%) and others in 4 patients (1, 5%). For chemotherapy, ABVD was given in 61% of cases and BEACOPPesc in 27% of the cases. The median number of previous treatment lines before BV was 2 (range 0-9): 72 (27%) patients received BV in second line, 131 (49%) in third line and 56 (21%) beyond the third line. Six (2%) unfit patients with comorbidities received BV as part of first-line treatment. At BV initiation, median age was 39 (18-90) years: 62 (23%) patients were ≥ 60 years; 63% were male; Ann Arbor stage was III-IV in 65%; performance status was 0-1 in 89%; and B symptoms were present in 26%. BV was initiated mainly for relapse/progression in 150 (57%) and refractory in 70 (26%) patients.
The main indication for the second line treatment with BV was failure of the frontline treatment (83%), with intent of transplantation after BV in 171 (65%) patients (autologous in 141 patients, allogeneic in 30 patients). BV was used in monotherapy in 34% of HL patients or in combination with chemotherapy in 66% (mainly bendamustine or GVD regimen). The median number of BV cycles was 4 for all HL patients (IQR 3 - 6) and for patients who received BV+chemotherapy (IQR 3 -6). The overall response rate was 59% for all HL patients treated with BV; 115 (43%) patients proceeded to transplantation BV consolidation accounted for 7% of cases 104 of 265 (39%) patients discontinued BV and median time from initiation to discontinuation was 8 months if planned by physicians, 4 months for adverse events, 3 months for autologous transplantation, 4 months for allogeneic transplantation and 4 months if due to progression.

**Conclusions:** In the pooled data of the 2015, 2016 and 2017 cohorts of a French national observational study, BV was mainly prescribed after a median of 2 previous lines of treatment, often in combination with chemotherapy 66%, for a median of 4 cycles and as a bridge to transplantation in eligible patients.

**Keywords:** autologous stem cell transplantation (ASCT); brentuximab vedotin; Hodgkin lymphoma (HL).

**Disclosures:** Sibon, D: Consultant Advisory Role: Takeda. Coulibaly, C: Employment Leadership Position: Takeda. Casasnovas, O: Consultant Advisory Role: Takeda. Bouabdallah, R: Consultant Advisory Role: Takeda. Brice, P: Consultant Advisory Role: Takeda.

460
BRENTUXIMAB VEDOTIN SALVAGE
FOLLOWED BY CONSOLIDATION POST
AUTOLOGOUS HEMATOPOIETIC STEM
CELL TRANSPLANTATION IN HIGH RISK
RELAPSED REFRACTORY HODGKIN
LYMPHOMA

M. Damlaj | A. Alaskar | G. Gmati | K. Abuelgasim |

B. Alahmari | S. Ghazi | A. Alhejazi | M. Alzahrani

Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

**Introduction:** Brentuximab vedotin (Bv) improves PFS post autologous HCT in high risk relapsed/refractory classical Hodgkin Lymphoma (r/r
PFS In Recipients of Bv based Salvage Followed by Post HCT Bv Consolidation

<figure><img src="image_279.png" /></figure>

Overall Survival In Recipients of Bv based Salvage Followed by Post HCT Bv Consolidation

<figure><img src="image_280.png" /></figure>

cHL). Furthermore, chemoimmunotherapy salvage with Bv results in a higher rate of complete metabolic response (CMR) compared with chemotherapy alone as shown by multiple groups. Attainment of such CMR status prior to HCT is highly predictive of prolonged remissions.

**Aim:** To examine the outcome of Bv containing salvage followed by consolidation in high risk r/r cHL. Primary endpoint was overall response rate (ORR) including rate of CMR. Secondary endpoint was 2-year PFS and overall survival (OS).

**Methods:** Pts with high risk r/r cHL whom were candidates for curative HCT were identified and all records were retrieved retrospectively after IRB approval. High risk r/r cHL was defined as patients with primary refractory disease, relapse within 12 months of front line therapy or relapse with extranodal disease. Patients received Bv with salvage at 1.8 mg/kg on day 1 of each cycle. Post-HCT Bv consolidation was given starting day 30-45 at 1.8 mg/kg every 3 weeks for up to 16 cycles. Response assessment was done in accordance with the Lugano criteria including the definition of CMR as deauville score ≤

3. OS and PFS were computed using Kaplan-Meier method with log-ranks test.

**Results:** A total of 20 patients were identified and all records retrospectively collected. Baseline characteristics were as follows; 11 (55%) male with median age at HCT of 22 years. 12 (60%) had refractory disease with median time to relapse following front line therapy of 3.7 months. Bv was given with IGEV in 14 (70%), ESHAP in 4 (20%) and Bendamustine in 2 (10%). The ORR was 100% and all patients had evidence of partial response or better. Furthermore, 14 (70%) of patients achieved CMR status pre-HCT.

A total of 19 patients were collected during salvage with GCSF while the remaining patient was mobilized with GCSF alone. Median CD34 x10⁶/kg collected was 12.75 (2.51-42.5) and the median time to ANC and platelet engraftment was 12 (9-15) and 16 (11-20) days, respectively. Post HCT, all patients received Bv consolidation with a median number of doses of 12 (3-16). Observed adverse events on Bv consolidation were; grade 3 neutropenia in 9 (45%) requiring GCSF support
in all and dose reduction in 6 (30%), neuropathy grades 1-3 in 2 patients (15%), 3 (15%) and 1 (5%) leading to early discontinuation of planned consolidation in 4 (20%). Neuropathy resolved or improved in all cases. A total of 2 patients relapsed, both while on Bv consolidation. Median follow up was 15.4 months (3.8-56) with estimated 2-year PFS and OS of 83% and 95%, respectively as shown in table 2 and figure 1 A-B.

**Conclusion:** Use of Bv containing salvage followed by post-HCT consolidation resulted in excellent outcomes in high risk r/r cHL and did not impact stem cell mobilization. Adverse events were common but manageable. Longer follow up and further validation of these observations are warranted.

**Keywords:** brentuximab vedotin; classical Hodgkin lymphoma (cHL); Deauville's criteria.

## 461 BRENTUXIMAB VEDOTIN PRIOR TO ALLOGENEIC STEM CELL

### TRANSPLANTATION IN HODGKIN'S LYMPHOMAS: A RETROSPECTIVE EXPERIENCE BY THE RETE EMATOLOGICA PUGLIESE (REP)

F. Gaudio¹ | P. Mazza² | A. Mele³ | G. Palazzo² |

A. Carella⁴ | D. Pastore⁵ | N. Cascavilla⁴ |

V. Pavone³ | G. Specchia¹

¹Haematology, Policlinico Hospital, Bari, Italy; ²Haematology, "G. Moscati" Hospital, Taranto, Italy; ³Haematology, "G.Panico" Hospital, Tricase (LE), Italy; ⁴Haematology, "Casa Sollievo della sofferenza" Hospital, San Giovanni Rotondo (FG), Italy; ⁵Haematology, "A.Perrino" Hospital, Brindisi, Italy

Allogeneic SCT is an effective treatment modality for HL patients suffering relapse or progression after autologous SCT. However, the success of this treatment modality is largely dependent on the tumour being sensitive to salvage therapy before transplantation This study reports a retrospective multicentre experience of the Rete Ematologica Pugliese (REP) over the past 16 years, aiming to compare the patient characteristics and outcomes of 21 BV pre-treated patients to 51 patients who received reduced-intensity conditioning (RIC) allogeneic SCT without prior BV.

72 patients with cHL who received allogeneic SCT were retrospectively studied. Prior use of BV had no effect on either engraftment or on the incidence and severity of acute graft versus host disease (GVHD). Indeed, there was a lower incidence of chronic GVHD in the BV group, with a 43% cumulative incidence at 3 years versus 47% in the no BV group, although this was not statistically significant.

Despite the low incidence of chronic GVHD, we did not observe a worse survival in the BV-treated group: 3-year progression-free survival (PFS) was 53%, 3-year overall survival (OS) was 62%, 3-year non relapse mortality (NRM) was 19%. In the no-BV group the 3-year PFS was 33%, 3-year OS was 44%, 3-year NRM was 16%.

In patients who were chemorefractory at the time of transplant, we found a statistically significant difference in PFS between the BV and no BV group (51% vs. 10% - p=0.029).

In conclusion, patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT. However, chemorefractory patients pretreated with BV prior to transplant have a better survival, implying that BV can improve the outlook after allogeneic SCT. The decrease in chronic GVHD is an interesting finding that needs to be further studied in the allogeneic SCT setting, also for diseases other than HL.

**Keywords:** allogeneic stem cell transplant (alloSCT); brentuximab vedotin; classical Hodgkin lymphoma (cHL).

## 462 COMBINATION OF NIVOLUMAB AND BENDAMUSTINE IN PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA

N.B. Mikhailova | K.V. Lepik | E.V. Kondakova |

P.V. Kotselyabina | A.V. Kozlov | Y.R. Zalyalov |

M.O. Popova | E.S. Borzenkova | I.S. Moiseev |

V.V. Baykov | B.V. Afanasyev

Raisa Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation, First Saint Petersburg State Pavlov Medical University, Saint-Petersburg, Russian Federation

**Introduction:** Immune checkpoints inhibitors therapy had shown significant activity in patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL). However, disease relapse or progression is observed in the majority of patients. One potential approach to enhance the effect of anti-PD1 therapy is a combination with chemotherapy. Bendamustine is a bifunctional alkylating agent with antimetabolite properties that had demonstrated activity for the treatment of r/r cHL and therefore may be the candidate drug for a combined regimen.

The aim of this analysis was to evaluate the safety and the efficacy of nivolumab (nivo) and bendamustine (benda) combination in patients with relapsed r/r cHL.

**Methods:** This analysis included 41 adult patients (26 m/15 f) with a median age of 31 years (21-62). The median number of previous therapy lines was 6 (3-11). Among all patients, 38/41 (93%) had received nivo in monotherapy with the median number of infusions 18 (4-27), and one patient received 12 infusions of pembrolizumab. The previous treatment also included auto-HSCT in 18/41 (44%) of patients, 21/41 (51%) had prior treatment with brentuximab vedotine, 23/41 (56%) had prior treatment with benda. According to LYRIC criteria, the status of the patients at the moment of nivo/benda combination was disease progression (PD) in 54%, indeterminate response (IR) in 27%, stable disease (SD) in 10%, partial response (PR) 10%. Patients were treated in a 28-day cycle for up to 3 cycles. Benda (90 mg/m2) was infused on day 1,2 and nivo (3 mg/kg) on day 1 of the cycle.
Toxicity was graded according to the NCI CTCAE (version 4.03). After treatment completion, the responses were evaluated by PET-CT scan and assessed by investigators using LYRIC criteria.

**Results:** Median follow-up time was 21 months (range; 4-28) from the start of combined treatment. The objective response rate among all treated patients was 80% with the 44% CR rate; 5 (12%) patients had an IR and 1 patient - SD. The PD was the best response in 2 patients. Median OS was not reached, 39/41 (95%) of patients were alive at the time of analysis. Median PFS was 10 mo (7-12) with 32% of patients alive and free of disease progression. Twelve patients undergo allo-HSCT. Adverse events (AE) during treatment were observed in 36 (88%) of patients. The most common AE were fatigue (76%), nausea (66%), pruritus (37%), headache (37%). Grade 3-4 adverse events included 2 cases of leucopenia and thrombocytopenia, uveitis, colitis, pneumonia, infusion reaction in 1 case each. All cases of immune related AE resolved completely after treatment with glucocorticosteroids.

**Conclusions:** This analysis shows that nivo and benda combination have promising activity in the treatment of r/r cHL with a manageable toxicity profile. The combination showed efficacy despite the previous failure of the benda containing regimens or immune checkpoint inhibitors therapy. Nivo/benda combination may be used as the bridge therapy for allo-HSCT in selected patients with r/r cHL.

**Keywords:** classical Hodgkin lymphoma (cHL); PD-1; salvage treatment.

## 463
RESPONSE TO NIVOLUMAB AS ≥3rd LINE THERAPY IN PTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN'S LYMPHOMA (CHL) AND ITS IMPACT ON QUALITY OF LIFE IN RESPONDERS AND NONRESPONDERS

K. Lepik<fnref n="1" /> | N. Mikhaylova<fnref n="1" /> | E. Kondakova<fnref n="1" /> |

L. Tsvetkova<fnref n="1" /> | Y. Zalyalov<fnref n="1" /> | E. Borzenkova<fnref n="1" /> |

I. Moiseev<fnref n="1" /> | V. Baykov<fnref n="1" /> | T. Nikitina² |

N. Porfir'eva² | T. Ionova² | B. Afanasyev<fnref n="1" />

The goal of treatment of relapsed/refractory (r/r) cHL is to achieve long-term disease control with limited toxicity and complications of therapy and to improve patients' quality of life (QoL). We aimed to study response rates in pts with r/r cHL receiving nivolumab (Nivo) as ≥3rd treatment and to analyse QoL changes in responders and non-responders.

Pts with r/r cHL who received Nivo 3 mg/kg q2w till disease progression, intolerance/toxicity of Nivo or refusal were included in the study. Treatment response was assessed using CT/PET-CT in accordance with LYRIC criteria for response assessment of malignant lymphomas to immunotherapy. Safety was assessed in accordance with NCI CTCAE v. 4.03. For QoL assessment pts filled out RAND SF-36 and EQ-5D questionnaires, for symptom assessment - CSP-Lym 41-1w questionnaire; the data were analyzed at baseline, at 3 and at 6 mos after Nivo treatment start. Pts who achieved complete/partial response (CR/PR) were considered as responders (Rs), pts with disease progression (DP) - non-responders (nRs). For longitudinal QoL analysis paired t-test, Wilcoxon test and χ² test were used.

In total, 101 pts cHL were involved in the study: median age - 31 y.o., range 19-62, 52% males. All the pts received 2-10 previous treatment lines; 90 out of 101 pts received Nivo as part of a named patient program. At the time of diagnosis 63.4% pts had advanced stage (III-IV), 61.4% - primary chemotherapy resistance. Median follow-up - 25 mos (3-31). Adverse events (AEs) were reported in 87.1% pts (severe AEs of 3-4 grades -18.8%). At 3 mos of treatment response was registered in 51%pts (20.5% - CR, 30.8% - PR); 45% pts progressed and 4% had disease stabilization. Rs and nRs groups were similar by age and gender (p>0.05). Baseline QoL was dramatically worsened for all SF-36 scales in both groups. All the pts experienced symptoms before Nivo treatment start; >50% pts had moderate-to-severe symptoms. During 6 mos of Nivo treatment significant QoL improvement by almost all SF-36 scales was revealed both in Rs and nRs (p<0.05). Positive QoL changes were more pronounced in Rs, however QoL scales improved significantly in nRs as well. EQ VAS significantly improved during treatment in both groups: 59.5 before treatment vs 81.1 at 6 mos in Rs, 57.4 vs 76.2 in nRs, consequently (p≤0.001). The severity of the vast majority of symptoms (28/41) significantly decreased during 6 mos of treatment both in Rs and in nRs (p<0.05).

The results obtained in this observational study demonstrate that r/r cHL pts exhibit good response and tolerability to Nivo as monotherapy as well as experience dramatic QoL improvement and significant decrease of symptom burden. Nivo treatment is accompanied with QoL improvement and decrease of symptom burden both in responders and non-responders.

**Keywords:** Hodgkin lymphoma (HL); nivolumab.

**Disclosures:** Ionova, T: Research Funding: Principal Investigator BMS study.

## 464
REAL-WORLD HEALTHCARE RESOURCE UTILIZATION (HRU) OF CLASSICAL HODGKIN LYMPHOMA (CHL) PATIENTS (PTS) TREATED WITH ANTI-PD1 CHECKPOINT INHIBITORS IN THE UNITED STATES (US)

<footnote n="1">¹Department of Oncology, Hematology and Transplantation, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, I. P. Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russian Federation; ²Department of Oncology and Hematology, Multinational Center for Quality of Life Research, Saint-Petersburg, Russian Federation</footnote>
F. Laliberté¹ | M. Raut² | M. Duh³ | X. Yang² |

G. Germain¹ | S. Sen² | S. MacKnight¹ | K. Desai² |

P. Armand⁴

¹Health Economics & Outcomes Research, Groupe d'analyse, Ltée, Montréal, Canada; ²Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, United States; ³Health Economics & Outcomes Research, Analysis Group, Inc., Boston, United States;

⁴Medical Oncology, Dana-Farber Cancer Institute, Boston, United States

**Introduction:** cHL pts with relapsed/refractory (RR) disease who relapse after or are ineligible for autologous stem cell transplantation have a poor prognosis. Recently, the anti-PD1 monoclonal antibodies nivolumab (nivo) and pembrolizumab (pembro) were approved by the FDA (May 2016 and March 2017, respectively) as treatment options for RR cHL pts.

**Objective:** This study aims to describe real-world patient characteristics and HRU (hospitalizations and outpatient [OP] visits) among pts with RR cHL receiving pembro or nivo in the US.

**Methods:** A retrospective database analysis was conducted using Symphony Health's Patient Integrated Dataverse® (07/2014-06/2018). The date of the first dispensing or administration of pembro or nivo was termed the index date. Pts with ≥12 months of clinical activity prior to the index date, ≥1 hospitalization or ≥2 OP encounters with an ICD-9/10-CM diagnosis of cHL prior to the index date, no diagnosis of nodular lymphocyte-predominant HL, and ≥18 years of age were included. Baseline characteristics were assessed in the 12 months prior to the index date. HRU was evaluated over the follow-up period, from the index date to the end of clinical activity or data availability. Crude rates of hospitalizations and OP visits were expressed as rate per person per year (PPPY) to account for varying durations of observation across pts. Mean and median hospital length of stay (LOS) were reported.

**Results:** Among cHL pts, 92 received pembro and 225 received nivo. The mean age was 59 and 53 years among those treated with pembro and nivo, of whom 40% and 44% were female, respectively. Corresponding median (IQR) follow-up periods were 214 (92-325) and 249 (126-443) days. Mean baseline Quan-Charlson comorbidity index score for pembro and nivo pts was 4.9 and 4.0; 18% and 14% had depressive disorders, and 16% and 8% had substance-related/ addictive disorders, respectively. Of pembro pts, 7% had received nivo and 26% brentuximab vedotin (BV). Of nivo pts, none had received pembro, 40% BV, and 2% ibrutinib. Pembro and nivo pts had an average of 1.5 and 1.4 all-cause hospitalizations during the baseline period, respectively, while the corresponding rate of all-cause hospitalizations during follow-up was 0.9 and 1.3 PPPY with an associated mean [median] LOS of 3.1 [1.5] and 4.2 [2] days (Figure). The rate of all-cause OP visits during follow-up was 36.4 and 35.5 PPPY for pembro and nivo pts, respectively. The rate of cHL-related hospitalizations during follow-up was 0.1 and 0.4 PPPY for pembro and nivo pts, respectively, with an associated mean [median] LOS of 4.7 [1] and 7.4 [4] days.

<figure><img src="image_281.png" /><figcaption>Figure. Hospitalizations During Follow-up in cHL Patients Receiving Pembrolizumab or Nivolumab</figcaption></figure>

**Conclusion:** This real-world descriptive study attempts to provide an early assessment of pembro and nivo user profiles and HRU since their market approval in the US. cHL pts treated with pembro are found to be older at treatment initiation, with greater comorbidity burden and baseline hospitalization rates than the nivo group.

**Keywords:** classical Hodgkin lymphoma (cHL); nivolumab; Pembrolizumab.

**Disclosures:** Laliberté, F: Employment Leadership Position: Analysis Group; Research Funding: Merck & Co., Inc. Raut, M: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc. Duh, M: Employment Leadership Position: Analysis Group; Research Funding: Merck & Co., Inc. Yang, X: Employment Leadership Position: Merck & Co., Inc. Germain, G: Employment Leadership Position: Analysis Group; Research Funding: Merck & Co., Inc. Sen, S: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc. MacKnight, S: Employment Leadership Position: Analysis Group; Research Funding: Merck & Co., Inc. Desai, K: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc. Armand, P: Research Funding: Merck & Co., Inc.

465
RETREATMENT WITH NIVOLUMAB IN PATIENTS WITH R/R CLASSICAL HODGKIN LYMPHOMA AFTER DISCONTINUATION OF THE THERAPY WITH IMMUNE CHECKPOINT INHIBITORS

L. Fedorova | K. Lepik | N. Mikhailova |

E. Kondakova | Y. Zalyalov | V. Baykov |

E. Babenko | E. Borzenkova | L. Tsvetkova |

L. Stelmakh | B. Afanasyev

Oncology, Raisa Gorbacheva Memorial Research Institute of Children
Oncology Hematology and Transplantation, Pavlov First Saint Petersburg
State Medical University, Saint Petersburg, Russian Federation

**Introduction:** Immune checkpoint inhibitors (ICI) may allow to achieve a durable remission in patients with resistant or refractory (r/r) classical Hodgkin lymphoma. The population of patients who discontinued therapy due to various causes is increasing. In case of relapse after
the ICI treatment the optimal treatment is not yet defined. One of the
possible options is the retreatment of the patient with ICI. To date
there is lack of information regarding the retreatment of patients with
relapse after ICI cessation. Our aim was to determine the effective-
ness of nivolumab therapy in patients with r/r Hodgkin lymphoma
with relapse of disease after achievement of complete remission with
ICI and cessation of therapy.

**Methods:** This analysis included 20 patients (5 male/15 female) with median age 32 (20-47) years with r/r classical Hodgkin lymphoma who were treated with nivolumab (3 mg/kg every 14 days) and achieved CR. After nivolumab therapy was stopped the patients received no other treatment before the disease progression. Response was assessed by positron-emission tomography/computed tomography (PET/CT) using LYRIC criteria every 3 month. After relapse of disease the patients were retreated with nivolumab monotherapy or in combination with chemotherapy. Median follow-up after the retreatment initiation was 10 (6-14) months.

**Results:** In 20 patients previously treated with nivolumab the median number of cycles was 25 (18-30). CR was achieved after median of 6 (6-18) cycles. The median duration of therapy after CR achievement was 7 (1-15) months. Median follow-up after therapy discontinuation was 23 (13-24) months. At the time of analysis, all patients were alive. Eight (40%) out of 20 patients relapsed after therapy discontinuation. In 4 out of 8 patients relapse was confirmed by biopsy. Median time before the relapse was 11 (5-20) month. All patients had undergone the retreatment with nivolumab: 7 were treated with monotherapy and 1- in combination with chemotherapy. Doses of nivolumab were 3 mg/kg in 5 patients, 1,5; 1,0 and 0,5 mg/kg in one patient each. Six patients were evaluated for response: CR (n=3), PR (n=1), indeterminate response type 2 (n=2). The best response was achieved after median of 6 (6-12) cycles.

It is worth noting that 3 patients had adverse events after retreatment with nivolumab. Two of these patients did not have any complications during initial nivolumab treatment. Adverse events included pyrexia, thrombocytopenia and pneumonitis. In last case therapy was discontinued before resolution of complication, but the patient achieved the complete remission before therapy cessation.

**Conclusions.** This analysis demonstrates that patients with relapse after nivolumab discontinuation sustained sensitivity to nivolumab and achieved a response during retreatment with nivolumab monotherapy or with chemotherapy combination. Further research is needed to determine response rate and durability of response.

**Keywords:** classical Hodgkin lymphoma (cHL); nivolumab; PD-1.

466

RETROSPECTIVE COHORT STUDY TO
ASSESS THE PROGNOSTIC VALUE OF
BASELINE NECROSIS ON PET-CT IMAGING
IN HODGKIN LYMPHOMA

I. Chen¹ | N. Borges² | L. Winn² | W. Osborne² | 
G. Petrides¹

¹Radiology and Nuclear Medicine, Freeman Hospital, Newcastle upon Tyne, United Kingdom; ²Haematology, Freeman Hospital, Newcastle upon Tyne, United Kingdom

**Background:** Identifying prognostic markers at diagnosis is essential to determine optimal tailored therapy for patients. The presence of necrosis has been shown to be associated with inferior outcomes in patients with diffuse large B cell lymphoma. This retrospective cohort study assesses whether necrosis at baseline correlates with clinical outcomes in patients with Hodgkin lymphoma.

**Methods:** All available baseline PET-CT scans of patients diagnosed with Hodgkin lymphoma between January 2015 and December 2016 at a large UK teaching hospital were reviewed for evidence of tumour necrosis by a consultant radionuclide radiologist with a specialist interest in lymphoma. Potential necrosis identified on PET-CT was then confirmed visually and quantitatively on alternative imaging. The presence or absence of necrosis was correlated with prognostic markers (Total Metabolic Volume (TMV), Total Lesion Glycolysis (TLG) International Prognostic Index (IPI) (Hasenclever Index)) and response assessment (metabolic response, current remission status, relapse outcome and mortality).

**Results:** Fifty three patients' PET-CT scans were reviewed in total. Ten patients were confirmed to have necrosis on both PET-CT and alternative imaging. The presence of necrosis was associated with increased total mortality (40%) vs no necrosis (16%); Kaplan Meier survival analysis demonstrated a significant difference between the necrosis cohort compared with the no necrosis cohort using the log rank test (p = 0.042). The presence of necrosis did not correlate with other prognostic markers (TMV, TLG or IPI).

**Conclusion:** The presence of necrosis on baseline PET-CT scan in patients receiving frontline treatment for Hodgkin lymphoma significantly correlates with increased patient mortality. Tumour necrosis did not significantly correlate with other prognostic markers. Identifying high risk patients at diagnosis is important. The current UK practice of delivering more intensive frontline therapy to patients with a high IPI is suboptimal and intensifying treatment after a positive interim PET scan is also associated with poor outcomes. Robust prognostic markers at diagnosis are a priority for the management of patients with Hodgkin Lymphoma. This study has identified a new independent prognostic marker in Hodgkin Lymphoma and prospective clinical trials are required.

**Keywords:** Hodgkin lymphoma (HL); positron emission tomography (PET).

**Disclosures:** Osborne, W: Consultant Advisory Role: Roche, Takeda, Servier, Gilead, MSD; Honoraria: Roche, Takeda, Pfizer; Other Remuneration: Novartis. Petrides, G: Honoraria: Takeda and GE Healthcare.

467

PROGNOSTIC VALUE OF PRE-
TRANSPLANT PET/CT IN HODGKIN
LYMPHOMA