bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontline flumatinib versus imatinib in patients with chronic myeloid leukemia in chronic phase: Results from the China randomized phase III study.
Authors: Li Zhang , Meng Li , Zhang Yanli , Zhu Huanling , Cui Jiuwei , Sun Aining , Hu Yu , Jin Jie , Jiang Hao , Zhang Xi , Li Yan , Liu Qifa , Liu Li , Zhang Wanggang , Gu Jian , Qiao Jian-Hui , Liu Bingcheng , Zhang Fengkui , Guo Yong , Wang Jianxiang 
Published: March 2020

7004 Background: Flumatinib (FM), a derivative of imatinib (IM), is a novel BCR-ABL1 tyrosine kinase inhibitor (TKI). The aim of this open-label phase III study was to validate the efficacy and safety of FM in comparison with IM as frontline treatment in Chinese patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CML-CP). Methods: Randomization was stratified by Sokal score with a 1:1 allocation to each arm. Primary endpoints were major molecular response (MMR = BCR-ABL IS≤0.1%) rates at 6 and 12 months. Molecular responses were assessed at a central laboratory blinded to treatment allocations during the study. Efficacy endpoints were analyzed for the intention-to-treat populations. This study is registered with ClinicalTrials.gov, number NCT02204644. Results: 400 eligible patients were randomized and patient characteristics at baseline were similar in each arm. The full analysis set (FAS) consisted of 393 patients who received FM 600 mg (n = 196) or IM 400 mg (n = 197) tablets once daily. Compared with IM, FM resulted significantly higher induction of MMR rate (%; 95%CI) at 6 month (33.7; 27.06-40.29 vs 18.3; 12.88-23.67; P = 0.0005) and 12 month (48.5; 41.47-55.47 vs 33.0; 26.43-39.56; P = 0.0021) and also at 3 month (8.2; 4.33- 12.00 vs 2.0; 0.06-4.00; P = 0.0058). Significantly more patients in the FM than in the IM arm achieved a complete molecular response (BCR-ABL IS≤0.0032%) at 12 months. Early molecular response (BCR-ABL IS ≤ 10%) at 3 months and early CCyR at 6 months were also significantly higher with FM than IM (82.1; 76.78-87.50 vs 53.3; 46.33-60.27; P < 0.0001 and 60.71; 53.88-67.55 vs 49.75, 42.76, 56.73; P = 0.0332). FM has a safety profile similar to IM. The rates of grade 3/4 TEAEs of FM were similar to IM, 56.57% (112 of 198) vs 41.38% (87 of 196). However, the frequencies of some nonhematological and hematological adverse events were significantly lower in the FM than in the IM arm, such as rash (4.59% vs 12.63%, P = 0.0064) and eyelid edema (0.51 vs 14.65, P < 0.0001); leukopenia (30.61 vs 62.63, P < 0.0001) and neutropenia (30.10 vs 59.60, P < 0.0001). No specific TEAE was identified in each arm. Conclusions: This phase III study met its primary endpoints. Our study results suggest that FM is comparable to IM in its safety and superior in its efficacy profile at 3, 6 and 12 month time points. These results support FM as a frontline treatment option for patients with newly diagnosed CML-CP. Clinical trial information: NCT02204644.
Correlation of BRAF V600E mutation with cardiac involvement assessed by heart imaging in a monocentric series of 205 patients with Erdheim-Chester disease.
Authors: Bravetti Marine , Azoulay Levi-Dan , Cohen-Aubart Fleur , Emile Jean-François , Amoura Zahir , Cluzel Philippe , Haroche Julien 
Published: March 2020

7019 Background: Erdheim–Chester disease (ECD), an inflammatory myeloid neoplasm, is an histiocytosis associated with multisystem infiltration. Cardiovascular involvement in ECD is under-diagnosed and associated with poor outcome. The targetable BRAFV600Emutation is present in up to 70% of all ECD. Methods: Retrospective study of 205 patients (pts) with ECD who had cardiac imaging (195 MRI, 10 CT when MRI was contraindicated). We identified the types of lesions (infiltration, tumor, and effusion), localization (pericardial, myocardial, valvular) and consequences on cardiac function (coronary stenosis, atrial wall dyskinesia, diastolic and systolic functions). Results: 141 (68.8%) pts were male. 30 (14.6%) had mixed histiocytosis (mainly ECD + langerhans cell histiocytosis). BRAF mutation ( BRAFm) was found in 112 (54.6%) cases, while 59 pts (28.8%) were Wild Type (WT) and 34 pts (7.6%) had unknown BRAF status. Among the 205 cardiac imaging, 101 (49.3%) were abnormal. Cardiac involvement was found in 93 pts (49%). Among these, 72 had an impairment of the right ventricular atrioventricular sulcus (74%), 65 of the right atrium (RA) enclosure (69%). Alteration of Tricuspid Annular Plane Systolic Excursion was found in 15% and correlated with the size of the tumor. Pericardial involvement (effusion, thickening or contrast enhancement) was found in 59 pts (29%). Among BRAFm pts, 75 (67%) had a heart abnormality while 37 (33%) had normal imaging; Among WT pts 14 (23.7%) showed heart abnormality, whereas 45 (76.3%) had normal imaging (RR 2.8 (CI: 1.8-4.5); p = 1.8*10-7). A RA tumor was present in 51 (45.5%) BRAFm but only 6 (10.2%) WT pts respectively (RR 4.5 (CI : 2.0-9.8); p = 7*10-6). BRAFm was also associated with aortic infiltration (RR 1.76 (CI: 1.2–2.5)) and pericardial involvement (RR 2.12 (CI: 1.1–3.9), p = 0.0017). Conclusions: Cardiac infiltration is frequent in ECD (49.3%), especially RA tumor. BRAFm is associated with RA, aortic and pericardial involvements.
Time from randomization to first subsequent induction/salvage therapy (ST) in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) treated with inotuzumab ozogamicin (InO) in the phase 3 INO-VATE trial.
Authors: Jabbour Elias , Stelljes Matthias , Advani Anjali S. , DeAngelo Daniel J. , Wang Tao , Neuhof Alexander , Vandendries Erik , Kantarjian Hagop M. 
Published: March 2020

7025 Background: Additional salvage regimens are burdensome for R/R ALL patients (pts) due to therapy-associated toxicities, which may affect quality of life with poor efficacy. In INO-VATE (Kantarjian et al, NEJM 2016), pts receiving InO vs standard chemotherapy (SC) had significantly greater remission rates and longer overall survival; after study treatment discontinuation, overall fewer STs (mainly burdensome chemotherapies) were used in the InO group vs SC. Methods: Study design was published. Adults with CD22+ ALL who were due to receive 1st or 2nd salvage treatment were randomized 1:1 to InO (n = 164) or SC (n = 162). Time to the first ST (TST) was time from randomization to the start of the first ST. Pts who did not receive any ST were censored. Data cutoff: Jan 4, 2017. Results: Fewer InO pts had ST vs SC pts (Table). Among the censored pts, 83/108 (76.9%) in the InO vs 54/69 (78.3%) in the SC group died, 23/108 (21.3%) vs 5/69 (7.2%) were alive at the end of the study, and 2/108 (1.9%) vs 10/69 (14.5%) were no longer being followed for survival. TST was longer in pts receiving InO vs SC. Overall median (95% CI) TST was 18.8 (14.7–NA) vs 3.9 (2.4–5.1) months; hazard ratio (HR) = 0.34, 97.5% CI: 0.23–0.49, 1-sided P< 0.0001. For pts (InO: 85, SC: 126) who never received hematopoietic stem cell transplantation (HSCT) on study, fewer InO pts had ST vs SC pts; TST was significantly longer in InO vs SC. For pts (InO: 70, SC: 18) who had HSCT directly after salvage, TST was extended in InO vs SC. Conclusions: In this study, treatment with InO provided the benefit of extended TST, effectively allowing patients a longer time period until an ST was needed in both patients who proceeded to as well as those who did not proceed to HSCT. Clinical trial information: NCT01564784. [Table: see text]
Nonclinical safety assessment of AMG 553, an investigational anti-FLT3 CAR-T therapy.
Authors: Karbowski Christine M , Goldstein Rebecca , Frank Brendon , Kim Kei , Li Chi-Ming , Gibson Bradford , Homann Oliver , Hensley Kelly , Brooks Ben , Yan Qinghong , Hernandez Rocio , Adams Gregor , Boyle Michael C , Arvedson Tara Lynn , Lebrec Herve 
Published: March 2020

7032 Background: FMS-like tyrosine kinase 3 (FLT3) is a tyrosine-protein kinase involved in hematopoiesis. In acute myeloid leukemia (AML), higher FLT3 transcript levels, independent of the presence of FLT3 mutations, correlate with higher leukocyte counts and higher degrees of bone marrow infiltration by leukemic cells. FLT3 protein is detectable on the cell surface of more than 80% of leukemia isolates from adult AML patients whereas FLT3 mutations are present only in approximately one third of patients. AMG 553 is a novel, investigational, adoptive cellular immunotherapy for the treatment of relapsed refractory AML, consisting of autologous T cells genetically modified ex vivo to express a transmembrane chimeric antigen receptor (CAR) to target FLT3 protein on the surface of AML cells irrespective of FLT3 mutational status. Methods: The nonclinical safety evaluation of AMG 553 includes assessment of FLT3 expression in normal tissues; in vitro assessment of cytotoxicity against human cells with or without FLT3 expression; toxicology studies in cynomolgus monkeys administered autologous T-cells transduced with an anti-FLT3 CAR or administered anti-FLT3 bi-specific T-cell engager (BiTE) antibodies. Results: Assessment of FLT3 expression in normal tissues indicates that FLT3 protein is detected on the cell surface of a subpopulation of human bone marrow hematopoietic stem and progenitor cells; expression in other tissues is cytoplasmic and not anticipated to be accessible to AMG 553. AMG 553-induced cytotoxicity was only observed in a percentage of primary bone marrow CD34+ cells. There was no evidence of CAR-T cell-mediated toxicity, expansion, or persistence in cynomolgus monkeys likely due to restricted cell surface FLT3 protein expression in healthy animals which demonstrates the limited value of such studies for this target. All findings in toxicology studies with anti-FLT3 BiTEs were consistent with the targeted killing of cells expressing FLT3 on the plasma membrane. Conclusions: The nonclinical safety data support AMG 553 as a novel therapeutic to target FLT3 protein on AML cells irrespective of FLT3 mutational status, while only affecting a percentage of normal hematopoietic stem and progenitor cells.
Phase II trial of CPX-351 (cytarabine:daunorubicin) liposome injection in patients with acute myeloid leukemia >60 years of age who have not been treated with intensive chemotherapy.
Authors: Ritchie Ellen K. , Lee Sangmin , Desai Pinkal M. , Ball Jeff , Samuel Michael S. , Curcio Tania , Miah Sumaiya , Roboz Gail J. 
Published: March 2020

7044 Background: This study enrolled older patients without age limitation to intensive chemotherapy with CPX 351 allowing for prior treatment with low intensity regimens for MDS or AML. Methods: 30 patients aged ≥65yrs with diagnosed AML received up to two induction cycles and consolidation cycles of CPX-351 as a first intensive therapy. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day mortality. Secondary efficacy endpoints included response rate and duration, and assessment of the relationship between cognitive function and treatment outcome. Although the primary efficacy endpoint data is pending, these interim results describe promising primary safety and efficacy endpoint results. Of the 30 patients enrolled, 10 patients (33.3%) were ≥75yrs old, 13 patients (43.3%) had had previous hematologic malignancies, 17 patients (56.6%) had adverse ELN risk stratification, and 16 patients (53.3%) had failed to respond to previous non-intensive treatments. In addition, all patients had an average of 2.1 co-morbid medical conditions. Results: 14 patients (47%) achieved best response criteria, with 12 patients (40.0%) achieving complete remission (CR) and 2 patients (6.6%) achieving complete remission with incomplete platelet or neutrophil recovery (CRi). 6 patients (20%) had a morphologic leukemia free state with pancytopenia and 10 patients had persistent disease. 8 patients (26.6%) went to stem cell transplant. 2 patients (6.6%) died within 30-days. Although final analysis on adverse events data is pending, 6 patients (20%) experienced a Grade 2 decrease in left ventricular ejection fraction (LVEF) at the end of first induction. Conclusions: These results suggest that in elderly AML patients regardless of age and prior treatment with non-intensive chemotherapy can be treated safely with CPX 351 with low 30 day mortality. CR in these patients is 40% with 26% going forward to stem cell transplant. Complete data will be assessed for OS and rate of MRD positivity. The relationship of cognitive and social factors to outcome will also be addressed.
Results from ongoing phase 1/2 clinical trial of tagraxofusp (SL-401) in patients with relapsed/refractory chronic myelomonocytic leukemia (CMML).
Authors: Patnaik Mrinal Mahesh , Ali Haris , Gupta Vikas , Schiller Gary J. , Lee Sangmin , Yacoub Abdulraheem , Talpaz Moshe , Wysowskyj Halyna , Shemesh Shay , Chen Janice , Brooks Christopher , Poradosu Enrique , Rupprecht Nicole , Pardanani Animesh Dev , Tefferi Ayalew , Wang Eunice S. , Taparia Minakshi , Verstovsek Srdan , Khoury Joseph , Pemmaraju Naveen 
Published: March 2020

7059 Background: Patients with chronic myelomonocytic leukemia (CMML) have historically poor outcomes, with ~6-7 mos median OS in relapsed/refractory (r/r) setting. Splenomegaly is a poor prognostic factor and potential target in CMML. CD123 is detected on blasts, monocytes, and neoplastic microenvironmental plasmacytoid dendritic cell (pDC) infiltrates part of the CMML malignant clone (Solary, et al). Tagraxofusp, a novel CD123 targeted therapy, demonstrated high levels of activity in BPDCN, an aggressive hematologic malignancy derived from CD123-expressing pDCs, and is FDA approved in BPDCN. As such, tagraxofusp may offer a novel approach in CMML. Methods: Multicenter, 2-stage Ph1/2 enrolling patients (pts) with r/r CMML. Objectives: determine optimal dose, evaluate safety and efficacy. Stage 1 dose escalation: IV tagraxofusp (7, 9, and 12 mcg/kg/day) dosed on days 1-3 every 21 days (C1-4), 28 days (C5-7), and 42 days (C8+). Stage 2 (ongoing), pts receive optimal S1 dose (12 mcg/kg/day; no MTD). Results: 20 pts (12 CMML-1; 8 CMML-2) enrolled. 18 pts 2nd-line (2 pts in 1L), HMAs most common prior therapy. Median age 69 (43-80); 81% male. 11 (52%) had baseline splenomegaly (spleen palpable below left costal margin by physical exam) of 2-27 cm. Most common TRAEs: hypoalbuminaemia (35%), thrombocytopenia (35%), nausea (30%), vomiting (30%), and fatigue (20%). Most common ≥Gr3 TRAEs were thrombocytopenia (35%) and nausea (5%). Capillary leak syndrome in 3 pts (15%; all Gr1&2). 100% (10/10) of pts with splenomegaly had spleen response: 80% (8/10) had reductions ≥50% and 67% (4/6) with spleen size ≥5 cm had reductions ≥50%. 3 pts achieved bone marrow complete responses, including 1 pt bridged to SCT in remission. Conclusions: Tagraxofusp demonstrated single agent activity in CMML as 80% of pts showed ≥50% reduction in splenomegaly by palpation. Splenomegaly in CMML, as in myelofibrosis, is a major cause of morbidity and associated with poor prognosis and impaired QoL. Targeting splenomegaly in myeloid neoplasms with proliferative features may be an important therapeutic goal. Given CD123 expression on CMML blasts, monocytes, and malignant pDCs, tagraxofusp may offer a targeted approach, especially in pts with splenomegaly. Updated safety and efficacy data to be presented. Registrational trial planned. Clinical trial information: NCT02268253.
Effect of fixed-duration venetoclax plus obinutuzumab (VenG) on progression-free survival (PFS), and rates and duration of minimal residual disease negativity (MRD–) in previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) and comorbidities.
Authors: Fischer Kirsten , Al-Sawaf Othman , Bahlo Jasmin , Fink Anna-Maria , Tandon Maneesh , Dixon Mark , Robrecht Sandra , Humphrey Kathryn , Böttcher Sebastian , Tausch Eugen , Humerickhouse Rod , Eichhorst Barbara , Wendtner Clemens-Martin , Langerak Anton W. , Kreuzer Karl-Anton , Goede Valentin , Stilgenbauer Stephan , Mobasher Mehrdad , Ritgen Matthias , Hallek Michael J. ,   CLL14 Study Investigators
Published: March 2020

7502 Background: The multinational, open-label, phase 3 CLL14 trial compared fixed-duration targeted VenG treatment with chlorambucil-obinutuzumab (ClbG) in previously untreated pts with CLL and comorbidities. Here we present endpoint analyses with particular emphasis on MRD− and PFS. Methods: Pts with a CIRS score >6 and/or an estimated creatinine clearance <70 mL/min were randomized 1:1 to receive equal duration treatment with 12 cycles (C) of standard Clb or Ven 400 mg daily in combination with G for first 6 C. Primary endpoint was PFS. MRD− in peripheral blood (PB) or bone marrow (BM) 3 months (mo) after treatment completion was a key secondary endpoint. MRD was analyzed serially from C4 every 3 mo by an allele-specific oligonucleotide polymerase chain reaction assay (ASO-PCR; cut-off, 10-4) and by next generation sequencing (NGS; cut-offs, 10-4, 10-5,10-6). Results: 432 pts were enrolled; 216 in each treatment group (intent-to-treat population). After 29 mo median follow-up, superior PFS was observed with VenG vs ClbG (HR 0.35; 95% CI 0.23–0.53; P<0.0001). MRD− by ASO-PCR was significantly higher with VenG vs ClbG in both PB (76% vs 35% [P<0.0001]) and BM (57% vs 17% [P<0.0001]) 3 mo after treatment completion. Overall, 75% of VenG MRD-negative pts in PB were also MRD-negative in BM vs 49% in the ClbG group. Landmark analysis for this timepoint by PB MRD status showed that MRD− was associated with longer PFS. Higher MRD− rates were achieved early and were more sustainable with VenG: 81% (VenG) vs 27% (ClbG) of pts were MRD-negative 12 mo after treatment completion; HR for MRD conversion 0.19; 95% CI 0.12–0.30 (median time off-treatment: 19 mo). MRD− rates by NGS confirmed these results; 78% (VenG) vs 34% (ClbG) of pts had MRD− at <10-4, 31% vs 4% at <10-6 and 35% vs 15% at ≥10-6–<10-5, respectively. Conclusions: Fixed-duration VenG induced deep (<10-6 in 1/3 of pts), high, and long lasting MRD− rates (with a low rate of conversion to MRD+ status 1 year after treatment) in previously untreated pts with CLL and comorbidities, translating into improved PFS. Clinical trial information: NCT02242942.
Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: A multicenter, open label, registration directed phase II study.
Authors: Fowler Nathan Hale , Samaniego Felipe , Jurczak Wojciech , Lech-Maranda Ewa , Ghosh Nilanjan , Patten Piers , Reeves James Andrew , Leslie Lori Ann , Chavez Julio C. , Ghia Paolo , Tarella Corrado , Burke John M. , Sharman Jeff Porter , Kolibaba Kathryn , O'Connor Owen A. , Cheah Chan , Miskin Hari P. , Sportelli Peter , Weiss Michael S. , Zinzani Pier Luigi 
Published: March 2020

7506 Background: Rituximab (RTX) alone or with chemo has substantially improved outcomes for patients (pts) with marginal zone lymphoma (MZL), but relapse is common and not all pts are candidates for or respond to current salvage therapies. Umbralisib is a novel, next-gen PI3Kδ inhibitor with unique inhibition of casein kinase-1ε (CK1ε) and a differentiated tolerability profile compared to earlier PI3Kδ inhibitors (Burris et al, 2018). This registration-directed study evaluates the efficacy and safety of umbralisib in pts with rel/ref (R/R) MZL. Methods: Pts had histologically confirmed MZL, ECOG PS ≤2, and ≥1 prior therapy including ≥1 anti-CD20 mAb-containing regimen. Pts received umbralisib 800 mg orally once daily until PD or unacceptable toxicity. The primary endpoint was overall response (ORR) as assessed by independent review (IRC) per 2007 IWG criteria. ORR by investigator assessment is reported here, and ORR by IRC is forthcoming. Secondary endpoints included duration of response (DOR), PFS, and safety. Results: 69 pts were enrolled; we report on the first 38 who are eligible for at least 6 months (mos) of follow-up as of the data cutoff. Among the 38 pts: extranodal (n = 23), nodal (n = 8), and splenic (n = 7). Median age was 67 years (range, 34-81). Median # of prior systemic therapies was 2 (range, 1-5). Seven pts (18%) had monotherapy RTX only, and 26 (68%) had at least one anti-CD20 mAb-containing chemoimmunotherapy. Median follow-up was 9.6 mos. ORR was 55% (4 CRs and 17 PRs). Eleven pts (29%) had stable disease (SD) of which 6 of these SD pts remain on study ranging from 7-12+ mos. The clinical benefit rate (CR+PR+SD) was 84%, and 91% of pts with at least 1 post-baseline assessment experienced tumor reductions. Median time to initial response was 2.7 mos, while median DOR was not reached (95% CI: 8.4-NR). The 12-month PFS was 71%. The most common all causality (≥20%) adverse events (AE) of any grade included: diarrhea (45%), nausea (29%), fatigue (26%), headache (26%), cough (24%), and decreased appetite (21%). The most common Grade 3/4 events were neutropenia (8%), febrile neutropenia (5%), and diarrhea (5%). As of the cutoff date 58% continue treatment. Conclusions: PI3Kδ inhibition with single-agent umbralisib is active and well tolerated in pts with R/R MZL, achieving durable responses with chemotherapy-free therapy. Clinical trial information: NCT02793583.
Phase 1/2 trial of acalabrutinib plus pembrolizumab (Pem) in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL).
Authors: Witzig Thomas E. , Maddocks Kami J. , De Vos Sven , Lyons Roger M. , Edenfield William Jeffery , Sharman Jeff Porter , Vose Julie , Yimer Habte Aragaw , Wei Helen , Chan Edward M , Patel Priti , Di Simone Christopher , Gandhi Mitul , Vaughn Jennifer , Kolibaba Kathryn , Cheson Bruce D. , Samaniego Felipe 
Published: March 2020

7519 Background: Acalabrutinib, a highly selective, potent, covalent Bruton tyrosine kinase (BTK) inhibitor, has a 24% overall response rate (ORR) as a single agent in R/R DLBCL. Pem targets PD-1, an immune checkpoint that limits anticancer responses. Pem showed responses in patients (pts) with Richter transformation who failed ibrutinib and can augment acalabrutinib activity in vitro. This study assessed acalabrutinib + Pem in R/R DLBCL. Methods: Pts with DLBCL, ≥1 prior chemoimmunotherapy and no prior allogeneic transplant received acalabrutinib 100 mg PO BID until progressive disease (PD) + Pem 200 mg/kg IV Q3W up to 2 y. Germinal center B-cell (GCB) vs non-GCB subtype was assessed by immunohistochemistry. Primary endpoint was safety. Results: Sixty-one pts (30 GCB; 31 non-GCB) were accrued, with a median age (range) of 67 y (30-85) and a median of 3 (1-8) prior therapies; 1 pt had prior autologous transplant. The most common Gr 3/4 adverse events (AEs) were neutropenia (15%) and anemia (11%). Gr 5 AEs were respiratory failure (n=3), sepsis, septic shock and abdominal abscess (n=1 each). All Gr atrial fibrillation was 5% (n=3), and major hemorrhage (≥ Gr 3) was 11% (4 gastrointestinal, 1 pulmonary, 1 epistaxis, 1 hematuria). Gr 3/4 immune-mediated events were elevated alanine aminotransferase (n=4), pneumonitis (n=2) and colitis (n=1). The ORR was 26% (Table) and was similar in GCB (27%) and non-GCB (26%) tumors. The median time on study was 5.2 mo (0.4-30.4+). Acalabrutinib/Pem discontinuations were due to PD (62%/56%) and AEs (15%/26%). As of June 2018, 10 pts remain on study; 6 on active therapy and 7 without PD. Conclusions: Acalabrutinib + Pem was well tolerated, with meaningful activity and some exceptional responders (>24 mo) in these R/R DLBCL pts. Randomized trials of the combination vs single agent are needed. Clinical trial information: NCT02362035. [Table: see text]