bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern of rasburicase (RAS) use in community oncology programs and impact on tumor lysis syndrome (TLS) outcomes.
Authors: Balcerski Wynter , Howard Scott C. , Napier Nicholas
Published: March 2020

e18559

Background: TLS complicates management of bulky chemosensitive cancers. Incidence and severity have increased with new, effective therapies. Prophylaxis/management vary widely. We assessed impact of RAS on outcomes of pts at risk for TLS. Methods: We examined medical records of 5860 pts newly diagnosed with hematologic cancers treated in 101 community hospitals (2010–2018) in the Guardian Research Network. We assessed TLS risk factors, use of uric acid-lowering therapy, e.g. RAS and TLS-related outcomes. RAS doses were grouped as very low/low: 0.01–0.09 mg/kg; medium/full: ≥ 0.1 mg/kg. Acute kidney injury (AKI) was defined using Risk, Injury, Failure, Loss, and End-stage kidney criteria. Early dialysis and early death occurred ≤ 30 days of diagnosis. Results: Of 5860 pts, 206 (3.6%) died early and 17 (0.3%) had early dialysis. AKI occurred in 441 (7.5%); 317 (72%) had AKI at presentation. TLS management varied by region, with RAS used in 4.7–8.1% (p < 0.001), and by baseline creatinine, with RAS used in 5.1% vs 38% (p < 0.001) with normal vs ≥ 3 mg/dL baseline creatinine, respectively. More than half of pts with elevated uric acid (EUA) or elevated creatinine (EC; > 2 mg/dL) at baseline did not receive RAS; they had disproportionate AKI (EC p < 0.001; EUA p < 0.001), early dialysis (EC p < 0.001; EUA p < 0.12) and early death (EC p < 0.001; EUA p < 0.001). Conclusions: Clinicians often use low RAS doses. Pts with hematologic cancers and EC and EUA at baseline have increased rates of AKI, early dialysis and early death. While immediate, aggressive supportive care for TLS is needed, it is inconsistently applied in this high-risk population. Funding Sanofi.
Outcomes of tbo-filgrastim, filgrastim-sndz or filgrastim for mobilization in patients undergoing an autologous hematopoietic stem cell transplant: A single center experience.
Authors: Neme Klodiana , Henkin David , Mikulandric Nancy , Grycki Meredith , Michael Angela , Smith Cassandra , Emole Josephine
Published: March 2020

e19000

Background: Studies have reported that use of filgrastim (G) or any biosimilar result in similar stem cell yield during hematopoietic stem cell mobilization, but little is known on the effect of these biosimilars on length of hospitalization for the transplant procedure, engraftment, and long term survival of autologous hematopoietic stem cell transplant (HSCT) patients. Beginning January 2017, the Henry Ford Cancer Institute (HFCI) began utilizing tbo-filgrastim (TBO) and filgrastim-sndz (SNDZ) as part of mobilization. This study was conducted to evaluate transplant specific outcomes in HSCT patients comparing biosimilar and reference filgrastim products. Methods: This study retrospectively evaluated all patients treated at HFCI who received G-CSF based mobilization for HSCT between 1/2017 and 11/2018. Patient-, mobilization- and transplant specific variables were collected and analyzed. Results: A total of 113 patients underwent stem cell mobilization followed by collection and autologous HSCT. Of the 73 patients analyzed, 62% had a diagnosis of Multiple Myeloma (MM), 22% had Non-Hodgkin Lymphoma (NHL). Approximately 45% of patients received TBO, 44% received G and remainder received SNDZ. The percentage of patients who proceeded to HSCT was 86%. There was no difference in adequate CD34+ yield among the three G-CSF products (P = 0.074). There was no difference in mobilization associated complications including bone pain and thrombocytopenia. Plerixafor use was similar among the groups (P = 0.55). Actual CD34+ (P = 0.31) and the number of apheresis sessions required to collect an adequate CD34+ yield (P = 0.30) were not different among the groups. No significant differences were noted in time to neutrophil (P = 0.96) or platelet engraftment (P = 0.91) and hospital length of stay (P = 0.78). We found similar rates of infection, febrile neutropenia, and mucositis among the three groups. Relapse rates were also similar among the groups. Conclusions: In our institution transplant related outcomes were similar among patients who received TBO, SNDZ, and G as part of their pre-transplant mobilization protocol.
Conceptual model of chronic lymphocytic leukemia.
Authors: Chung Helena , Blowfield Matthew , Krogh Calvin , Eek Daniel
Published: March 2020

e19001

Background: The study aimed to create a conceptual model (CM) of disease- and treatment-related signs, symptoms and impacts in patients with first-line (1L) or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Methods: The CM was based on literature searches, review of CLL patient blogs/forums, interviews with expert hematologists, and semi-structured concept elicitation interviews with 40 patients with CLL (20 1L, 20 R/R; with fatigue, weight loss, fever and/or night sweats in previous week). To identify salient concepts, the number of patients mentioning each concept and the concept’s mean disturbance rating (from 0 [not at all] to 10 [very]) were mapped. Results: Literature searches identified 32 prevalent concepts, with the most common being fatigue/tiredness. Patient blogs/forums revealed further symptoms (muscle/joint aches, headaches, weakness) and impacts (stress, fear of death, uncertainty). Clinicians reported recurrent infections and swollen lymph nodes as key signs of CLL and noted that fatigue is related to both symptoms (e.g. tiredness) and impacts (e.g. needing to rest and limit daily activities). In patient interviews, 50 concepts were revealed, with 42 present in both 1L and R/R; fatigue was the most prominent and impactful. Fatigue-related sub-concepts were identified, covering symptoms (tiredness/need to sleep, lack of energy, weakness, cognitive fatigue) and impacts (decreased ability to maintain social/familial/professional role, decreased physical functioning, frustration). Three versions of the CM were created: an overall model with all identified concepts, and two models highlighting the most salient concepts in 1L and R/R. Muscle/joint aches, night sweats, bruising, fatigue-related symptoms, fever and recurrent infections/illness were salient symptoms in both 1L and R/R, as were impacts such as anxiety/worry, stress, depression, financial difficulty, and fear of death. Shortness of breath and coughing were salient in 1L only, and swollen lymph nodes, headaches, pain/discomfort, weight loss, nausea/vomiting, and infusion reactions were salient in R/R only. Conclusions: The three versions of the CM can help to inform patient-centered end points to evaluate new treatments for 1L and/or R/R CLL.
Long-term effects of ibrutinib on blood pressure in patients with chronic lymphocytic leukemia (CLL).
Authors: Jones Jade , George Binsah , Peterson Christine B , Burger Jan Andreas , Jain Nitin , Wierda William G. , Keating Michael J. , Durand Jean-Bernard , Ferrajoli Alessandra
Published: March 2020

e19009

Background: Ibrutinb is approved for treatment of CLL. Hypertension (HTN) has been reported as a side effect of ibrutinib in 1-23% of patients. We previously reported HTN in CLL patients after 6 months of treatment with ibrutinib. In this study we describe the effects of long-term treatment with ibrutinib on blood pressure (BP). Methods: We performed a retrospective study, evaluating 150 CLL patients on ibrutinib-based clinical trials from 2010 to 2015. Patient demographics, co-morbidities, tobacco use, anti-HTN therapy were recorded. BP was evaluated at baseline and sequentially for up to 5 yrs. New onset HTN was defined as systolic BP (SBP) of ≥ 130 mmHg and/or diastolic BP (DBP) ≥ 80 on two separate visits with no prior HTN or anti-HTN therapy. An increase in baseline SBP by ≥10 and/or increase in DBP by ≥10 was considered significant regardless of the absolute BP. Univariate logistic regression analysis was performed to assess relationship of HTN risk factors and new HTN. Results: Patients’ median age was 65 yrs (68% male and 88% white). Median follow-up was 3 yrs. Pre-existing HTN was present in 44% of patients, 40% were on anti-HTN therapy prior to ibrutinib. New HTN developed in 65% of patients without prior diagnosis of HTN; 32 % of patients were started on anti-HTN therapy or received additional anti-HTN therapy. Of the patients who experienced an increase in BP, 33% experienced isolated systolic HTN. Median SBP was 130 at baseline, 132 at 1mo, 137 at 3mo, 135 at 6mo, 139 at 12mo, 138 at 3yrs, 144 at 5yrs (mean increase in SBP: 7.2, P < 0.001). In patients whose SBP was < 130 at baseline the median SBP was 119 at baseline, 122 at 1mo, 134 at 3mo, 130 at 6mo, 134 at 12mo, 135 at 3yrs and 141 at 5yrs (mean increase in SBP: 15.7, p < 0.001). 74% of patients experienced and increase in SBP ≥10. New HTN on ibrutinib was not associated with: tobacco use, obesity, chronic kidney disease or obstructive sleep apnea (p > 0.05). Conclusions: In this study we demonstrated a high rate of new HTN in patients on prolonged ibrutinib treatment. HTN in these patients is persistent, linear and independent of other risk factors. The increase in BP remained despite initiation of anti-HTN therapy. Additional studies are ongoing to define cardiovascular and renal complications associated with HTN in these patients.
Retrospective comparison of Cheson 2007 and Lugano classification criteria in independent review assessment of FDG-avid lymphomas.
Authors: Narang Jayant , Bajpai Surabhi , Jarecha Rudresh , Karve Sayali , Ludajic Katarina , Sharma Manish , Bohnsack Oliver
Published: March 2020

e19015

Background: Revised Response Criteria in Malignant Lymphoma (Cheson 2007) and Lugano Classification are the most commonly used guidelines to assess response to treatment in lymphoma in clinical trials. While not drastically different from Cheson 2007, important clarifications and modifications were provided in Lugano Classification, specifically in the use of PET in response assessments. Methods: We retrospectively compared the blinded independent review of 25 subjects across multiple studies, assessed using Cheson 2007 and Lugano Classification on separate case report forms by the same reviewer per subject on 2 different dates. Focus was given on comparison of endpoint assessments of Progression-Free Survival (PFS), Duration of Complete Response (DOCR) and Duration of Response (DOR). Results: Assessments using Lugano Classification showed increased DOCR in 12% (3 out of 25), and DOR in 24% (6 out of 25) of the subjects. Cheson 2007 showed better DOR in 8% (2 out of 25) of the subjects. For PET positivity, Lugano Classification requires comparison with liver and mediastinal blood pool, whereas Cheson 2007 requires comparison to background or mediastinal blood pool. The results suggest that this difference in assessment of PET positivity (blood pool versus liver) leads to achieving Complete Response (CR) earlier, leading to longer DOCR and DOR when assessed using Lugano Classification compared to Cheson 2007. Lugano Classification also showed longer PFS in 16% (4 out of 25) of the subjects. When Progressive Disease (PD) was due to identification of new lesion(s), the two criteria showed similar PFS; however, when PD was due to lesion measurements and PET positivity assessment, Lugano Classification showed a longer PFS. Better PFS in Lugano Classification was observed because enlarging lymph nodes do not always show increased PET activity. Conclusions: In Independent review assessments for FDG avid lymphoma, using Lugano Classification showed better DOCR, DOR and PFS as compared to Cheson 2007. Further studies with increased number of subjects and intra-reader variability assessments are warranted to investigate the two criteria.
Hodgkin lymphoma in United Arab Emirates UAE, epidemeology, histological types and treatments outcome: Case series of 47 cases from Mafraq Hospital, Abu Dhabi, UAE.
Authors: Maarraoui Aladdin , AlMessabi Ahmed , Al Teneji Omar , Maarraoui Yasmeen
Published: March 2020

e19016

Background: Approximately 9,050 Americans gets diagnosed annually with Hodgkin's Lymphoma HL and approximately 1,150 dies each year from HL(1).Nodular Lymphocyte-predominant LP (NLPHL) represents 5% of HL (2). Mafraq Hospital is a tertiary hospital in Abu Dhabi, UAE, We suspected that we are seeing more than expected cases of NLPHL.Therefore, we carried a retrospective study to review all cases of HL seen at our oncology unit for the period from 01/01/2016 till 30/06/ 2018. Methods: We developed Excel data collection tool. After Ethics approval, Electronic Medical Records of all cases seen with the diagnosis of HL between 01/2016 and 06/2018 at Mafraq Hospital were reviewed. Results: Total of 47 case were collected. 8 cases (17%) were found to have NLPHL, The rest of cohort were 39 cases, 22 (57%) of them had nodular sclerosis HL, 4 cases (10%) mixed cellularity HL, 2 (5%) lymphocyte rich HL, no cases of lymphocyte depleted HL. 9 (23%) of cases were classical HL with no type as diagnosis was made from core biopsies. 2 cases (5%) unlisted type.The stage for the 42 case were as follows Stage I: 1 case = 2.3%, Stage II: 24 case = 57.1%Stage III: 11 case = 26.1%Stage IV: 6 cases = 14.2%. Conclusions: We saw 23 (49%) females and 24 (51%) males. Our hypothesis that NLPHL is more frequently seen in UAE seems to be correct as 17% of all HL cases seen were from this subtype. Mean age at diagnosis of all HL cases is 33 years. In the NLPHL there were 2 (25%) females and 6 (75%) males. Mean age at diagnosis for NLPHL is 31.8 years. Most HL patients received ABVD as first line regimen. This is documented in 38 out of 47 case. Mean overall survival registered at the closure of the study is 45 months. It is important that this overall survival is premature as no patient has relapsed or died.
Disease characteristics of diffuse large B-cell lymphoma predicting relapse after autologous stem cell transplantation.
Authors: Gaut Daria , Oveisi David , Howell Grant , Romero Tahmineh , Schiller Gary J.
Published: March 2020

e19030

Background: High-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) is standard of care for patients with diffuse large B-cell lymphoma (DLBCL) whose diseases relapse after, or are refractory to, first-line therapy. However, there are still high rates of relapse following ASCT, and non-relapse mortality also affects survival rates. Prognostic indicators are therefore needed to identify the best candidates for HDC/ASCT. Methods: We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed, 33 refractory) who underwent HDC/ASCT at the University of California Los Angeles from 2010-2015. Results: The median age at the time of ASCT was 61 years (IQR 51.5-68.0). 80 patients (72%) had DLBCL in a complete response at the time of ASCT, and the majority (98 patients, 88%) had ECOG performance status of 0-1. After a median follow-up of 4.6 years (IQR 2.2-8.1), the 1-year progression-free survival (PFS) rate was 77.3% (95% CI 69.7%-85.7%) and the 1-year overall survival (OS) rate was 84.7% (95% CI 78.2%-91.7%). 41 patients (37%) relapsed after ASCT with a median PFS of 11 months (IQR 5.0-20.0). 37 patients (33%) died, 23 (21%) from relapse mortality, 11 (10%) from non-relapse mortality, and 3 (3%) from unknown cause of death. In univariate analysis, 2 variables were significantly associated with curtailed PFS and OS: higher number (≥ 3 vs < 3) of chemotherapy regimens prior to ASCT (HR 2.20, 95% CI 1.19-4.06, p = 0.013 for PFS; HR 2.01, 95% CI 1.06-3.84, p = 0.036 for OS) and higher International Prognostic Index (IPI) score at time of ASCT (trend HR 1.61, 95% CI 1.10-2.35, p = 0.018 for PFS; trend HR 2.02, 95% CI 1.37-2.98, p = 0.001 for OS). Higher National Comprehensive Cancer Network (NCCN) IPI score at time of ASCT (trend HR 2.29, 95% CI 1.34-3.90, p = 0.002) and refractory versus relapsed disease (HR 1.99, 95% CI 1.04-3.82, p = 0.038) were also significantly associated with curtailed OS. Conclusions: Our study suggests that IPI, while a validated prognostic tool at diagnosis, is also a prognostic indicator at time of ASCT for PFS and OS. NCCN IPI at time of ASCT was also found to be predictive of OS. Age-adjusted IPI was not associated with outcome following ASCT.
Efficacy of mogamulizumab in previously treated patients with less advanced mycosis fungoides: Results from the MAVORIC study.
Authors: Geskin Larisa J. , Scarisbrick Julia , Bagot Martine , Fisher David Christopher , Elmets Craig , Duvic Madeleine , Beylot-Barry Marie , Kim Ellen J. , Moriya Junji , Leoni Mollie , Zinzani Pier Luigi
Published: March 2020

e19031

Background: In the MAVORIC Phase 3 study, patients (pts) with previously treated mycosis fungoides (MF)/Sezary syndrome (SS) stage IB-IVB who received mogamulizumab (MOGA) had significantly prolonged progression-free survival and greater overall response rates (ORR) compared to pts on vorinostat (VORI) (Kim et al. Lancet Oncol 2018). Less advanced MF (stage IB/IIA) is a chronic skin malignancy that can involve blood and nodes and may require many lines of systemic therapy over the disease course. This post-hoc analysis specifically examined efficacy and safety of the recently approved MOGA in stage IB/IIA MF pts. Methods: In MAVORIC, stage IB-IVB MF/SS pts who were treated with ≥1 prior systemic therapy were randomized to MOGA or oral VORI. In the post-hoc analysis, time to next treatment (TTNT) was defined as time to any therapy excluding topical steroids or focal radiation treatment. ORR was based on global composite response in 4 disease compartments – skin, blood, lymph nodes, and viscera – achieved at 2 consecutive visits at least 8 weeks apart. Individual compartment responses were also assessed. Results: A total of 85 pts with stage IB/IIA MF were included (MOGA, IB n = 15, IIA n = 21; VORI, IB n = 27, IIA n = 22). Overall, 24% (10/42) of IB pts and 28% (12/43) of IIA pts had received ≥6 prior therapies. Median TTNT with MOGA in IB pts was 11.5 months (mo) (95% CI, 1.4,16.0) compared to 3.1 mo (95% CI, 2.7, 5.3) with VORI; in IIA pts, median TTNT was 10.1 mo (95% CI, 5.5, 12.6) and 4.9 mo (95% CI, 2.4, 8.0), respectively. ORR in IB pts receiving MOGA and VORI was 20% (3/15) and 18.5% (5/27), respectively; ORR in IIA was 19% (4/21) and 0% (0/22), respectively. With respect to stage IB and IIA, compartmental response rates with MOGA were: skin (20% [3/15], 38% [8/21]), blood (0% [0/2], 75% [6/8]), and lymph node (0% [0/0], 15% [3/20]), respectively. Adverse events were generally manageable and consistent with the ITT population. Conclusions: Though MAVORIC was not powered to determine treatment effect by disease stage, this post-hoc analysis of TTNT, ORR, and compartmental response in stage IB/IIA demonstrates meaningful clinical benefit with MOGA in previously treated, less advanced MF pts. Clinical trial information: NCT01728805.
Clinical characteristics and prognosis of primary breast lymphoma: Cleveland Clinic experience.
Authors: Kewan Tariq Zuheir , Covut Fahrettin , Thapa Bicky , Spiro Timothy Peter , Haddad Abdo S. , Daw Hamed
Published: March 2020

e19035

Background: Primary Breast lymphoma (PBL) is a rare form of extranodal non-Hodgkin lymphoma (NHL). The majority of PBL are diffuse large B-cell lymphoma (DLBL). Current treatments can achieve an overall survival of 5 years in 80% of the patients. We evaluated prognostic factors and survival rates in PBL patients at Cleveland clinic foundation (CCF). Methods: We retrospectively identified patients diagnosed with PBL at CCF between January 2004 and January 2018. Baseline characteristics were compared between the indolent and aggressive lymphoma groups using two sample T-test for continuous variables, chi-square test and fisher’s exact test for categorical variables. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 36 patients with PBL were identified, of whom 35 patients (97.2%) were females with a median age of 66 years (34-95). Of all patients, 23 (63.9%) were indolent lymphoma and 13 (36.1%) were aggressive lymphoma. The most common subtypes were marginal zone lymphoma (33.3%), DLBL (25%) and follicular lymphoma (19.4%). Only 2 patients (5.6%) had implant-associated anaplastic large T-cell lymphoma. There was significant difference in presentation between indolent and aggressive lymphoma patients; 78.3% of indolent lymphoma patients presented with incidental mammogram lesions compared to 30.8% of aggressive lymphoma patients (P-value = .019).Seventy five percent of the patients presented with stage IE, 16.7 % presented with stage IIE and 8.3% presented with stage IV. Treatment received included chemotherapy (55.6%), radiotherapy (47.2%), surgeries (16.7%), and rituximab (80% of patients received chemotherapy). Six patients (16.7%) didn’t receive treatment. Only one patient received central nervous system prophylaxis. Median follow-up of patients was 37.1 months. Three-year OS for patients with indolent and aggressive PBL was 94.4% (95% CI 84.4% - 100%) and 90.9% (95% CI 75.4% - 100%), respectively (p = 0.69). Conclusions: Marginal zone lymphoma was the most common subtype in our cohort. Indolent lymphoma commonly present as incidental mammogram finding. Prognosis of PBL is not affected by histologic subtype, tumor stage and bilateral breast involvement. Current treatments achieve good control of the disease.
Phase 2 study of parsaclisib (INCB050465) for relapsed or refractory diffuse large b-cell lymphoma (DLBCL) (CITADEL-202).
Authors: Coleman Morton , Belada David , Casasnovas René-Olivier , Gressin Rémy , Lee Hui-Peng , Mehta Amitkumar , Munoz Javier , Verhoef Gregor , Corrado Claudia , DeMarini Douglas James , Zhao Wanying , Chen Xuejun , Fay Keith
Published: March 2020

e19038

Background: Parsaclisib, a potent, highly selective, next-generation PI3Kδ inhibitor, showed preliminary efficacy as monotherapy for relapsed or refractory non-Hodgkin lymphoma, including DLBCL (Abstract 410, ASH 2017), in a phase 1/2 study. This phase 2 study further assessed parsaclisib in patients (pts) with relapsed or refractory DLBCL (NCT02998476). Methods: Pts enrolled into 2 groups (A, Bruton tyrosine kinase [BTK] inhibitor naïve; B, BTK inhibitor experienced) and received oral parsaclisib 20 mg QD for 8 wks, then 20 mg QW. In a planned interim futility analysis conducted in the first 40 pts treated in Group A, if ≤13 (≤32.5%) responded by IRC assessment, Group A was to be terminated. Results: At data cutoff (22 Jun 2018), 60 pts (Group A, n = 55; Group B, n = 5) were treated (median age, 71 y [range, 36—94]; men, 63.3%; ≥3 prior systemic therapies, 60%). At the planned interim analysis in Group A, ORR (by PET) was 25% (10/40 pts; 5 CMR, 5 PMR); the futility boundary was crossed. At data cutoff, ORR in Group A was 25.5% (14/55 pts; 8 CMR, 6 PMR); median PFS was 2.2 mo (95% CI: 2.0‒4.1); median DOR was 4.5 mo (95% CI: 2.1‒5.1). ORs were observed in germinal center B-cell (GCB) and non-GCB subtypes. ORR in Group B was 20% (1/5 pts; 1 CMR). The most common non-hematologic treatment-emergent adverse events (TEAEs) occurring in > 10% of all pts (all grade [Gr]; Gr 3/4) were rash events (21.7%; 1.7%), colitis/diarrhea events (16.7%; 5%), nausea (16.7%; 0%), cough (15%; 0%), and pyrexia (15%; 8.3%). Gr 3/4 AST and ALT elevations occurred in 5% and 1.7% of pts, respectively; Gr 3/4 neutropenia and anemia occurred in 5% of pts each. The most frequent ( > 5%) serious TEAEs were pyrexia (8.3%), general physical health deterioration (6.7%), and hypercalcemia (6.7%). TEAEs led to therapy discontinuation in 7 pts (2 treatment-related), dose interruption in 20 pts (10 treatment-related), and dose reduction in 3 pts (all treatment-related). Median duration of therapy was 57.5 d (range, 11–318). Conclusions: Parsaclisib monotherapy using a QD followed by QW dosing regimen was well tolerated with no new safety signals reported. Further evaluation of parsaclisib in all subtypes of DLBCL is ongoing in a combination study Clinical trial information: NCT02998476.
Tumor-associated myeloid derived suppressor cells of granulocytic nature as a potential biomarker for prognostication of response in treatment of diffuse large cell lymphoma.
Authors: Mukherjee Kalyan Kusum , Dhar Sukanya , Chakraborty Mohona , Bhattacharjee Rajib , Bhanja Shayani , Das Subhadip , Ghosh Sarbari , Sarkar Madhurima , Dasgupta Shayani , Ghosh Diptendu , Bose Anamika , Baral Rathindranath
Published: March 2020

e19040

Background: NHL is a type of lymphoma either B or T cell origin. However, 85% is of B cell type, especially diffuse large B cell lymphoma (DLBCL) with CD20+ in nature. Standard of care of CD20+DLBCL is R-CHOP 6 to 8 cycles and 66% patients generally respond to this treatment. Remaining 34% is still unresponsive to R-CHOP. Thus, establishment of a biomarker is required to intensify the treatment.Out of different scope of biomarker development, alterations in immune cellular components within tumor microenvironment may be tried as a potential biomarker to assess the possibility of occurrence of residual disease and relapse within 2 years for the DLBCL patients with 6-8 cycles of R-CHOP. Methods: 51 of selected pt.CD20+ DLBCL were treated with 6-8 cycles of R-CHOP and included in the present study. A panel of immune cells CD4+, CD8+ T cells, CD4+CD25+FoxP3 regulatory T cells, CD33+CD11b+CD14-/+ MDSCs and CD8+CD45RO+ Memory T cells were studied by flow-cytometry at different phases of treatment. Results: Within 51selected patients, 9 were disease free and 11patients exhibited stable disease for 2years (stable, non-relapsed, n = 20) following the completion of treatment. Rest of the patients (n = 31) showed relapse in different time periods within 2 years. Among several immune cells, CD33+CD11b+MDSCs were remarkably elevated in high grade residual and relapsed DLBCL patients compared to non-relapsed patients and normal healthy individuals. CD33+CD14- granulocytic, but not CD33+CD14+ monocytic MDSCs are mostly increased in relapsed patients than those having stable disease. CD4+CD25+FoxP3 regulatory T cells are also elevated in relapsed DLBCL patients, but increment is not comparable as MDSCs. No significant alteration was noticed in CD4+ and CD8+ T cells. Among relapsed patients CD8+CD45RO+ Memory T cells are increased, those are mostly corrupted in nature. Conclusions: Observed correlation between increased granulocytic MDSCs with the occurrence of residual disease and/or relapse suggests granulocytic MDSCs might be a potential biomarker for prediction of residual and relapse for DLBCL patients.
Durability of complete response after blinatumomab therapy for refractory/relapsed aggressive B-cell non-Hodgkin lymphoma.
Authors: Viardot Andreas , Hess Georg , Bargou Ralf C. , Morley Nicholas , Gritti Giuseppe , Iskander Karim , Cohan David , Zhang Alicia , Franklin Janet , Coyle Luke
Published: March 2020

e19041

Background: Achieving durable response in patients (pts) with relapsed/refractory (R/R) aggressive B-cell lymphoma (B-NHL) is challenging. Blinatumomab, a bispecific T-cell engager (BiTE) immunotherapy targeting CD19-expressing cancer cells, has shown promising efficacy in pts with R/R aggressive B-NHL. We report the durability of complete response (DOCR) in pts treated with blinatumomab. Methods: The DOCR in pts with R/R aggressive B-NHL responding to blinatumomab was assessed using data from two phase 2 studies (study 1 [N = 25], NCT01741792; study 2 [N = 41], NCT02910063) in pts with R/R aggressive B-NHL. CR was assessed using Cheson (study 1) and Lugano (study 2) criteria. Time-to-event variables were analyzed using the Kaplan-Meier (KM) method. Results: Baseline pt characteristics in the pooled analysis were: median age 59 years (range, 4177); 54% men; 54% treatment refractory; median 2 lines of prior therapy (range, 17); and 15% with prior autologous hematopoietic stem cell transplant. Of 25 pts treated with blinatumomab in study 1, 4 (16%) evaluable pts achieved CR. Of 41 pts treated with blinatumomab in study 2, 9 (22%) achieved CR. Median DOCR was not reached (Table). At a median follow-up of 9.1 months in the pooled analysis, 3 pts (23%) had relapsed (study 1, n = 2 [50%]; study 2, n = 1 [11%]). At 12 and 18 months, the KM probability of maintaining CR in the pooled analysis was 53.0% (95% confidence interval [CI], 8.5, 85.0). Conclusions: For pts with R/R aggressive B-NHL who received blinatumomab, a durable response is possible. Longer-term follow up is needed to fully characterize the DOCR to blinatumomab. Clinical trial information: NCT01741792; NCT02910063. [Table: see text]
A core laboratory approach to large-scale radiomics and machine-learning prediction of DLBCL outcomes after first-line treatment using results from the phase III GOYA study.
Authors: Chauvie Stephane , Dalmasso Federico , Pierce Larry , Nielsen Tina , Sahin Deniz , Lee Calvin , Mattiello Federico , Kostakoglu Lale , Kinahan Paul
Published: March 2020

e19042

Background: We are using the phase 3 GOYA study to retrospectively investigate using quantitative image texture features (i.e. radiomics, evaluating tumor heterogeneity) to improve the prognostic value of baseline FDG-PET. We report on the considerations for analysis, which is ongoing, and solutions to methodological challenges. Methods: GOYA, an open-label, randomized, phase 3 study, enrolled 1418 patients from 207 centers; 1334 had a baseline FDG-PET scan with detectable lesions. Image data with annotated regions of interest (ROIs) defined by qualified physicians were transferred to the Cuneo imaging core laboratory. Images were interpolated to a common 4x4x4 mm voxel size and ROI masks using 4 different definition methodologies were used to define image sub-volumes that contained the lesions. Large ROIs in normal liver were also defined. The 42 Haralick radiomic image texture features were computed using the PET oncology radiomics test suite. Results: A total of 9286 lesions were analyzed. Interpolation of images to a fixed size is challenging in this cohort due the large number of features to be computed (~1.5M). As a test, the lesions were differentiated from liver ROIs using 5 classifiers (e.g. support vector machine, random forest, etc) with an accuracy of 0.995–0.999. The mean (±SD) of the metabolically active tumor volume was 21.2±22.2 mL (range 0.2–146 mL) with a preponderance of smaller lesions as shown by the median of 15.0 mL. The skewed distribution had downstream effects on many of the quantitative (e.g. total lesion glycolysis) and radiomic image texture features. The majority of texture features were computable; 5 (Coarseness, Contrast, Busyness, Complexity, Texture Strength) required interpolation to a 2x2x2 mm voxel size, requiring extended computation time. FDG-PET images came from a variety of PET/CT scanners; thus, a unified image reconstruction protocol was not possible. Conclusions: Radiomics analysis of large phase 3 imaging trials is feasible. However, careful attention should be paid to the entire processing chain, including tests for non-computable features values due to highly skewed distributions and lesion size. Clinical trial information: NCT01287741.
SYK inhibition with fostamatinib in Waldenström's macroglobulinemia: In vitro cell based assays.
Authors: Markovtsov Vadim , Masuda Esteban
Published: March 2020

e19047

Background: Waldenström's macroglobulinemia (WM) is characterized by accumulation of IgM secreting neoplastic B cells in the bone marrow (BM). B-cell antigen receptor (BCR) signaling plays a pivotal role in the regulation of integrin-mediated retention of lymphoma cells in the BM. Signaling through the BCR leads to activation of spleen tyrosine kinase (SYK) and downstream kinases which play a role in lymphoma pathobiology. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib targets BCR-controlled signaling and integrin-mediated adhesion in WM cells, but patients with WM may become refractory to ibrutinib treatment. As SYK signaling is upstream of BTK, we explored the effect of the SYK inhibitor R406 (the active metabolite of fostamatinib) on BCR mediated signaling and cell adhesion in WM. Methods: MWCL-1 cells were treated with R406, CAL101 (PI3 kinase inhibitor) or ibrutinib at concentrations up to 10µM and stimulated with anti-IgM antibodies or PMA. The cells were transferred to plates coated with fibronectin to assess cell adhesion. For the proliferation assays, MWCL-1 cells or primary B cells were pretreated with kinase inhibitors, followed by stimulation of primary B cells with anti-IgM. Results: Anti-IgM or PMA alone stimulated the adhesion of MWCL-1 on fibronectin. The addition of R406 had a comparable effect to ibrutinib on inhibition of IgM mediated cell adhesion (IC50 = 0.32µM), consistent with the effect of both compounds on BCR mediated signaling. Neither compound affected PMA induced cell adhesion, indicating that the effect on IgM mediated cell adhesion was not due to toxicity. Lack of off-target toxicity was further confirmed in the MWCL-1 proliferation assays where the compounds showed less potency than in BCR-mediated assays. Comparable inhibition of adhesion and proliferation was seen with CAL101. Conclusions: Preliminary preclinical studies with R406 show that SYK is involved in BCR mediated signaling and cell adhesion in WM. CAL101 mediated inhibition of adhesion further confirmed the role of SYK, which is upstream of PI3K. R406 was as effective as ibrutinib in blocking WM cell adhesion. Further studies of SYK inhibition with fostamatinib as a potential treatment option for WM are warranted.
Cost-Effectiveness of brentuximab vedotin with chemotherapy in frontline treatment of CD30-expressing peripheral T-cell lymphoma.
Authors: Feldman Tatyana , Zou Denise , Rebeira Mayvis , Lee Joseph , Harris Mack , Ma Wenkang , Fanale Michelle A. , Manley Thomas John , Feliciano Joseph , Rao Shangbang , Kansal Anuraag
Published: March 2020

e19060

Background: The most common frontline treatment for peripheral T-cell lymphoma (PTCL) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen. In the recently reported phase 3 ECHELON-2 trial, brentuximab vedotin (BV) in combination with CHP (A+CHP) demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) compared to CHOP, with a manageable safety profile. The objective of this analysis was to evaluate the cost-effectiveness of A+CHP in the frontline setting for CD30-expressing PTCL. Methods: A partitioned survival model consisting of 3 health states (PFS, post progression survival, and death), was constructed using clinical and quality of life data from ECHELON-2 from a US payer perspective over a lifetime time horizon. PFS and OS observed from ECHELON-2 were extrapolated using standard parametric distributions. The best-fitting distributions (log-normal for both arms) were selected based on statistical goodness of fit and clinical plausibility of the long-term projections. Health utilities were derived from the European Quality of Life 5-Dimensions (EQ-5D) data collected in ECHELON-2. The average utility scores for the pre- and post-progression periods were estimated via a repeated-measures mixed-effects model. Medical resource use and costs were from literature. Results: The model predicted A+CHP extended undiscounted PFS by 2.92 and OS by 3.38 years over CHOP. These survival gains drive the value in the model. After adjusting for quality of life and discounting, A+CHP was associated with 1.79 quality-adjusted life years (QALYs) gained at an incremental cost of $176,842, yielding an incremental cost-effectiveness ratio (ICER) of $98,987. Sensitivity analyses of alternative model assumptions provided ICERs from $64,000 to $154,000. The estimated probability that A+CHP is cost-effective compared with CHOP was 75% at a willingness-to-pay threshold of $150,000. Conclusions: Based on the ECHELON-2 trial data, this analysis showed for patients with previously untreated CD30-expressing PTCL, treatment with BV in combination with CHP is likely to be cost-effective in comparison to CHOP.
GX-G3, a long-acting G-CSF, compared with pegfilgrastim in reducing duration of severe neutropenia after chemotherapy for non-Hodgkin’s lymphoma.
Authors: Ertan-Ahmed Senem , Kiehl Michael G. , Radinoff Atanas , Graklanov Vasko , Tzvetkov Nikolay , Mihăescu Rodica , Özatlı Düzgün , Atalay Figen , Turgut Burhan , Cho Seok-Gu , Rekhtman Grygoriy , Sahin Adem , Oncel Hatice , Choi Yuri , Yang Sang-In , Choi Yoon-Jeong , Heo MinKyu , Sung Young Chul
Published: March 2020

e19065

Background: G-CSF is used in patients at significant risk for developing severe neutropenia (neutrophil count < 0.5 × 109/L or grade 4 neutropenia) following myelosuppresive chemotherapy. GX-G3, human G-CSF fused to hyFc is a proposed alternative to Neulasta. Methods: An open-label, randomized, phase II study was designed to compare the effects of subcutaneous (SC) injection of GX-G3 (a long-acting G-CSF) at doses of 150, 250 and 350 μg/kg with Neulasta 6 mg administered SC in patients receiving R-CHOP for advanced NHL (n = 65). The primary objective was to assess the duration of severe neutropenia after 1st cycle of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). The following parameters were also assessed: duration of severe neutropenia after 2nd cycle of chemotherapy, optimal time for GX-G3 intervention (two GX-G3 250 μg/kg cohorts; administered 24 and 72 hours after R-CHOP), incidence of severe neutropenia and febrile neutropenia post R-CHOP, pharmacokinetics, and safety. Patients were randomly assigned to receive GX-G3 or reference drug, Neulasta, one dose after 1st and 2nd cycle of R-CHOP for a total of 2 doses. Results: The mean duration of severe neutropenia after 1st cycle was shortest in GX-G3 350 μg/kg group [GX-G3 150, 250 (24h, 72h), 350 μg/kg and Neulasta®; 3.2, 2.3, 2.0, 1.3 and 2.4 days, respectively]. The results of all GX-G3 groups and Neulasta were not significantly different for duration of severe neutropenia after 2nd cycle of R-CHOP, incidence of severe neutropenia and febrile neutropenia, or toxicity profile. The elimination half-life of GX-G3 and Neulasta ranged from 29.8 to 66 hours and 19.2 to 76.8 hours, respectively. Conclusions: GX-G3, in all tested dosage regimen, was safe and well tolerated in this patient population. A single injection of GX-G3 per chemotherapy cycle provided neutrophil support with safety and efficacy similar to that provided by Neulasta. GX-G3 administration after 24 hours, compared to 72 hours post R-CHOP treatment resulted in relatively shorter duration of severe neutropenia. Clinical trial information: 2015-002693-20.
Post-transplant lymphoproliferative disorder-related admissions in the United States.
Authors: Yu Arlene , Acharya Prakash , Singh Seema , Durdevic Momcilo , Stan Andreea , Nimkar Abhishek , Elenius Henrik , Jesmajian Stephen , Naaraayan Ashutossh
Published: March 2020

e19071

Background: Post-transplant lymphoproliferative disorders (PTLD) is an immunosuppression-related malignancy complicating solid organ transplant (SOT) and non-solid organ transplant (NSOT) (peripheral stem cell and bone marrow transplant). The epidemiology of PTLD-related hospital admissions (PRA) is unclear. The objective of our study is to describe the trend and outcomes of PRA in the United States. Methods: A descriptive, retrospective study was conducted using the National Inpatient Sample database from 2009-2014. PRA were selected using International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis code (238.77). Multivariate regression analysis was performed to determine mortality and length of stay (LOS) in PRA. Results: The incidence of PRA in transplant-related hospital admissions was 7.19 per thousand admissions (pta) in 2009 and 7.24 pta in 2014 with annual percentage change (APC) of 0.1% (p = 0.9). The median age of patients with PRA was 47 (25-75 percentile: 19-61) years, 38.8% were females, 69.9% were white and 10.7% were African-American. Among patients with PRA, 91.1% had SOT [kidney (31.4%), liver (20.9%), heart (14.6%), lung (7%) and small intestines (1.89%)]; 7.1% had NSOT [bone marrow (3.9%) and peripheral stem cell (2%)] and 1.8% had two or more organ transplants. The most common principal diagnosis in PRA were complications of organ transplant (33.3%), encounter for anti-neoplastic chemotherapy (11.4%), neutropenia (5%), acute kidney injury (3.7%) and hearing loss (1.7%). Among transplant-related hospital admissions, PRA had higher adjusted odds of inpatient mortality [Odds ratio (OR) 2.57 (Confidence Interval (CI) 1.69-2.42), p < 0.001] and longer LOS [4.22 days (CI 3.26-5.17), p < 0.001] than non-PRA. Among PRA, those with NSOT have higher adjusted odds of mortality [OR 2.98 (CI 1.07-8.29), p = 0.036] and longer LOS [16.27 days (CI 3.51-29.03), p < 0.013] compared to those with SOT. Conclusions: PRA have higher odds of mortality and longer LOS compared to other transplant-related hospital admissions. Even though SOT accounts for most of the PRA, the adjusted odds of mortality are significantly higher in PRA with NSOT.
Clinical and cytogenetic features of nonsecretory multiple myeloma (NSMM) in the era of novel agent induction therapy: The Mayo Clinic experience.
Authors: Nandakumar Bharat , Gonsalves Wilson I. , Buadi Francis , Dispenzieri Angela , Dingli David , Lacy Martha , Kapoor Prashant , Lin Yi , Kourelis Taxiarchis , Muchtar Eli , Go Ronald S. , Warsame Rahma M. , Hayman Suzanne R. , Leung Nelson , Hwa Lisa , Fonder Amie L. , Kyle Robert A. , Gertz Morie A. , Rajkumar S. Vincent , Kumar Shaji
Published: March 2020

e19519

Background: NSMM is a rare subtype of myeloma that has not been well characterized in the era of novel agent induction therapy. Thus, we evaluated the clinical and cytogenetic features of patients with newly diagnosed NSMM evaluated at our institution. Methods: We evaluated all NSMM patients seen at the Mayo Clinic, Rochester from 2008-2017 based on the absence of a detectable monoclonal protein in their serum and urine electrophoresis and having a concurrent involved serum immunoglobulin light chain of less than 5 mg/dL. Survival analysis was performed by the Kaplan-Meier method and clinical and cytogenetic features were reported descriptively. Results: This cohort consisted of 30 consecutive patients with NSMM with a median age of 62 years (40-79) of which 16 (53%) were male. The median bone marrow plasma cell involvement was 70% (Range: 0 – 100). There were 3/25 (12%) patients who presented with a creatinine of 2 mg/dL or greater and 6/23 (26%) patients who presented with hypercalcemia (11 mg/dL or greater). The ISS classification of this cohort is as follows: Stage 1- 8 (36%) patients, Stage 2- 3 (14%) patients and Stage 3- 11 (50%) patients. There were 6 (21%) out of 28 patients with high risk cytogenetics (either del 17p, t(4;14), t(14;16) or t(14;20). The distribution of primary cytogenetic abnormalities among this cohort was as follows: t(11;14) – 16 (57%), t(4;14) – 1 (4%), trisomies – 6 (21%) and other - 5 (13%). The median overall survival (OS) for patients in this cohort was 59 months (95% CI: 34 – 64). In comparison to a control cohort of newly diagnosed secretory myeloma patients matched for age, gender and year of diagnosis in a 1:2 ratio, the median OS was worse for the NSMM cohort but this was not statistically significant (59 vs. 92 months, p = 0.257). Conclusions: Patients diagnosed with NSMM had a predisposition towards having a t(11;14) primary cytogenetic abnormality. In the era of novel agent induction therapy, they may have a survival outcome that may be worse than newly diagnosed secretory myeloma patients.
Can autologous stem cell transplantation abrogate the poor prognosis associated with high LDH in myeloma patients?
Authors: Ilhan Osman , Cengiz Seval Guldane , Toprak Selami Kocak , Civriz Bozdag Sinem , Yuksel Meltem Kurt , Topcuoglu Pervin , Arslan Onder , Ozcan Muhit , Demirer Taner , Akan Hamdi , Beksac Meral , Gurman Gunhan
Published: March 2020

e19524

Background: Multiple myeloma (MM) is a plasma cell neoplasia characterized by a diffuse clonal plasma cell infiltration of the bone marrow. Serum lactate dehydrogenase (LDH) is a relevant biomarker in MM and in the era of novel agents, LDH confirmed its negative impact on survival in newly diagnosed setting (Bal et al., presented at ASH2018). Methods: This single center retrospective study included 208 patients with a diagnosis of MM who underwent ASCT at our center between January 2008 - Mart 2018 were prospectively analyzed. We identified patients with baseline serum LDH values (ULN = 247 U/L). We compare baseline characteristics and outcomes of ASCT according to LDH values. Results: All clinical data were available in 208 cases (High LDH: 92 (44.2%), Normal LDH: 116 (55.8%)) There were 87 (41.8 %) female and 87 (41.8 %) male patients. The median age at diagnosis of MM was 63 years (range, 37-77 years). The median time of follow-up was 48 months (range, 2.8-197.5 months). Of the 92 patients with high LDH who underwent ASCT, median age was 65 years and ECOG performance status was 1 and 58.6 % were male. There was no statistically differences in performance status, induction treatment regimens and the number of treatment line prior to ASCT. Induction therapy consisted of 3 drugs in 91.3% and 2 drugs in 8.7 % in high LDH group (p = NS). Forty-eight (53.3%) patients with high LDH received a bortezomib-based induction and 35 patients (40.2 %) achieved ³ very good partial remission (VGPR) after the induction therapy. During follow up, 45 relapses were occurred and all relapsed patients died. According to the long-rank test, estimated 5-year OS was not significantly different between normal and high LDH categories (63.3 %±0.6 % vs. 64.6 %±0.5 %; p = 0.99). Median PFS was 101.4 months (95% CI: 73.7-129) in high LDH group and 92.1 months (95% CI: 71.1-113.1) in normal LDH group (p = 0.99). Conclusions: Elevated LDH was confirmed as a poor prognostic factor in previous reports. In our transplanted patients with high LDH cohort, clinical outcomes are favorable and similar those have normal LDH. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant LDH levels on ASCT outcomes.
Treatment patterns and outcomes among t(11;14) myeloma patients in a real-world setting.
Authors: Norden Andrew David , Mathura Shivam , Hansen Eric , Goldberg Stuart L. , Siegel David Samuel DiCapua
Published: March 2020

e19531

Background: There is uncertainty about the prognostic and predictive significance of t(11;14), long considered a standard risk cytogenetic abnormality in multiple myeloma (MM). This translocation is associated with elevated BCL-2 expression which may explain responses to venetoclax that have been reported previously. In a real-world database derived from EMR data, we sought to characterize real-world treatment patterns and outcomes from this unique MM cohort. Methods: Records for MM patients with t(11;14) diagnosed between 2000 and 2017 were identified in the COTA real-world database. Descriptive statistics were used to summarize the data. Results: 399 MM patients with t(11;14) were identified. Patient characteristics are summarized in the Table. The most frequent first-line treatments were bortezomib + dexamethasone + lenalidomide (134, 33.6%), bortezomib + cyclophosphamide + dexamethasone (69, 17.3%), and bortezomib + dexamethasone (60, 15.0%). Six (1.5%) patients received venetoclax. Response and progression-free survival data are being analyzed and will be presented at the meeting. Median overall survival was 14.3 (95% CI 10.4 – not yet reached) years. Conclusions: Real-world databases are useful in describing treatment patterns and outcomes in narrowly defined cohorts such as MM with t(11;14). The OS result reported here is unexpectedly long and will be fully explored prior to presentation. [Table: see text]