bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of efficacy and safety with obinutuzumab plus chemotherapy versus rituximab plus chemotherapy in patients with previously untreated follicular lymphoma: Updated results from the phase III Gallium Study.
Authors: Townsend William , Buske Christian , Cartron Guillaume , Cunningham David , Dyer Martin J.S. , Gribben John G. , Zhang Zilu , Rufibach Kaspar , Nielsen Tina , Herold Michael , Hiddemann Wolfgang , Marcus Robert 
Published: May 2020

8023 Background: Immunochemotherapy is standard of care for patients (pts) with previously untreated advanced stage follicular lymphoma (FL). Four-year data from the Phase III GALLIUM study (NCT01332968) have previously demonstrated an improvement in the primary endpoint of investigator-assessed progression-free survival (PFS) for obinutuzumab (GA101, G) plus chemotherapy (G-chemo) versus rituximab plus chemotherapy (R-chemo) (Townsend et al. ASH 2018). Here, we report efficacy and safety results from an updated analysis. Methods: Eligibility criteria: ≥18 years; advanced stage, previously untreated grade 1–3a FL; requiring treatment according to Groupe d’Etude des Lymphomes Folliculaires criteria. Pts were randomized 1:1 to receive G 1000mg IV (day [D] 1, 8 and 15 of Cycle 1; D1 of each subsequent cycle) or R 375mg/m2 IV (D1 of each cycle) with CHOP, CVP, or bendamustine for 6 or 8 cycles. Responders received maintenance therapy with the same monoclonal antibody every 2 months for 2 years. Results: 1202 pts (median age 59 years) were enrolled (n = 601 per treatment arm). Median duration of follow-up was 76.5 months. Pts receiving G- vs R-chemo demonstrated improved PFS (5-year PFS: hazard ratio [HR] 0.76; 95% CI: 0.62–0.92; p = 0.0043; 70.5% [95% CI: 66.4–74.1] vs 63.2% [95% CI: 59.0–67.1]). There was no notable difference in 5-year overall survival (OS), with few events in either arm (HR 0.87; 95% CI: 0.62–1.22; p = 0.41; G-chemo: 90.2% [95% CI: 87.5–92.4]; R-chemo: 89.4% [95% CI: 86.6–91.6]). Time-to-next-treatment (TTNT) was greater in the G- vs R-chemo arm (5-year TTNT rate: HR 0.72; 95% CI: 0.57–0.90; p = 0.0039; 79.7% [95% CI: 76.1–82.7] vs 72.9% [95% CI: 69.1–76.4]). Incidence of grade 3–5 adverse events was 79.3% in the G-chemo arm and 71.2% in the R-chemo arm, and consistent with those reported in the primary analysis (Marcus et al. N Engl J Med 2017). Conclusions: These data further demonstrate the clinically meaningful and durable benefit of treatment with G-chemo relative to R-chemo in previously untreated FL pts. Acknowledgement: GALLIUM was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of William Townsend, was provided by Louise Profit and Stephanie Lacey of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd. Clinical trial information: NCT01332968 .
Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: Follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial.
Authors: Al-Sawaf Othman , Zhang Can , Tandon Maneesh , Sinha Arijit , Fink Anna Maria , Robrecht Sandra , Tausch Eugen , Schary William L. , Ritgen Matthias , Wendtner Clemens Martin , Kreuzer Karl A , Eichhorst Barbara , Stilgenbauer Stephan , Hallek Michael J. , Fischer Kirsten ,   CLL14 Study Investigators
Published: May 2020

8027 Background: The CLL14 trial demonstrated significant improvement of progression-free survival (PFS) with fixed-duration venetoclax-obinutuzumab (VenG) as compared to chlorambucil-obinutuzumab (ClbG) in patients with previously untreated CLL and coexisting conditions. Here, we report follow-up data on safety and efficacy. Methods: Patients with previously untreated CLL and coexisting conditions were randomized 1:1 to receive 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab. Primary endpoint was investigator-assessed progression-free survival. Key secondary endpoints were response rates, rates of minimal residual disease (measured every 6 months up to 5 years after last patient enrolment) and overall survival. Follow-up is ongoing but all patients are off study treatment. This trial was registered with ClinicalTrials.gov, number NCT02242942. Results: Of the 432 enrolled patients, 216 were randomly assigned to receive VenG and 216 to receive ClbG. After a median follow-up of 39.6 months (interquartile range 36.75 - 43.04), progression-free survival continued to be superior for VenG as compared to ClbG (median not reached vs 35.6 months; hazard ratio [HR] 0.31 [0.22-0.44], p < 0.001). At 3 years, the estimated progression-free survival rate was 81.9% in the VenG arm and 49.5% in the ClbG arm. This benefit was consistently observed across all clinical and biological risk groups, including patients with TP53 mutation/deletion and unmutated IGHV status. Of note, PFS was also significantly longer for VenG treated patients with mutated IGHV status. Assessment of minimal residual disease 18 months after end of treatment showed that 47.2% of patients in the VenG arm had undetectable (u) uMRD ( < 10−4), 13% had low (L)-MRD (≥ 10−4 and < 10−2) and 7.9% high (H)-MRD (≥ 10−2), compared to 7.4% uMRD, 17.1% L-MRD, 26.9% H-MRD in the ClbG arm. No difference has been observed (HR 1.027, 95% CI 0.602-1.753, p = 0.921) for overall survival; median overall survival has not been reached in either group. Second primary malignancies were reported in 36 (17%) patients in the VenG arm and 22 (10.3%) in the ClbG arm. No new safety signals were observed. Conclusions: The results suggest that the superior efficacy and deep remissions after fixed-duration VenG are maintained during extended follow-up, and show the long-term benefits of 12 cycles of VenG across all known risk categories. Clinical trial information: NCT02242942 .
Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.
Authors: Hwang Steven R , Higgins Alexandra , LaPlant Betsy , Maurer Matthew J. , Ansell Stephen M. , Thanarajasingam Gita , Bennani N. Nora 
Published: May 2020

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.
Mantle cell lymphoma: initial report from the North American Mantle Cell Lymphoma Consortium.
Authors: Fu Kai , Yu Guohua , Bi Chengfeng , Cheng Hongxia , Smith Lynette , Yuan Ji , Naushad Hina , Link Brian K. , Nichols Craig R. , Barr Paul M. , Kahl Brad S. , Stewart Douglas , Barta Stefan K , Beaven Anne , Advani Ranjana H. , Martin Peter , Greiner Timothy , Weisenburger Dennis , Armitage James O. , Vose Julie 
Published: May 2020

8035 Background: The goal of the North American Mantle Cell Lymphoma (MCL) Project is to evaluate the clinical, biological, and genomic markers that affect the outcome of patients with MCL. Methods: We have retrospectively studied the clinical and pathological features of 307/421 patients diagnosed with MCL between January 2000 to December 2012 from 23 institutions across North American. Results: The male to female ratio of MCL patients was 3.5:1, with a median age of 66 years (range: 24-106 years). Approximately 29% of patients (78/269) presented with B symptoms and 257 (257/307, 83.7%) patients had extranodal involvement at diagnosis. Median follow-up was 7.1 years (range, 0.03 to 16.6 years) with the five-year PFS and OS at 27.8%, and 54.4%, respectively. Univariate analysis revealed that the following factors were significantly associated with both inferior OS and PFS ( p< 0.05): older age (≥60 years), presence of B symptoms, advanced Ann Arbor stage, elevated LDH, low platelets (≤100K/ml), blastoid/pleomorphic cytology, Ki67 proliferation ≥30%, circulating tumor cells, no transplantation (vs. transplantation), and allogeneic (vs. autologous) stem cell transplantation. In addition, large tumor size (maximal diameter > 3cm), high WBC ( > 10×103/ml), CD5 or CD23 positivity, and a complex karyotype were associated with inferior OS ( p< 0.05). Multivariate Cox regression analysis showed age (≥ 60y; p= 0.0028, HR = 2.44, 95% CI: 1.36-4.38) and high LDH ( p= 0.0062, HR = 2.19, 95% CI: 1.25-3.84) were the two factors predicting the clinical outcome. MIPI-c, a commonly used prognostic scoring system which includes Ki67, stratified the 100 MCL cases into four group with distinct clinical outcomes ( p< 0.001). Using readily-available clinical and pathological variables, we developed a simple and robust scoring system, MIPI-P (pathology), which consisted of age (≥60 years), LDH (high), Ki67 index (≥30%), Ann Arbor stage (III/IV), and cytological type (blastoid/pleomorphic), each contributing one point. The MIPI-P system stratified 104 MCL cases into three distinct groups ( p< 0.001). Median survival for the different groups were: low grade (0-1 points): 11.8 years; intermediate grade (2-3 points): 4.9 years; and high grade (4-5 points): 1.6 years. We further validated this system in an independent cohort of 33 MCL cases and confirmed that the modified MIPI-P provided robust prognostic predication ( p= 0.014). Conclusions: The clinical and biologic characteristics of MCL can provide information assisting with the prognosis of patients with MCL.
Real-world outcomes of elderly patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR-T) therapy.
Authors: Fitzgerald Lindsey , Kittai Adam , Nastoupil Loretta J. , Waller Alexandra , Jacobson Caron A. , Saucier Anna , Kamdar Manali K. , Spradley Janet , Denlinger Nathan , Chipman Jonathan , Hu Boyu 
Published: May 2020

8039 Background: CAR-T has drastically improved outcomes for R/R DLBCL patients (pts). While CAR-T is now standard of care for the treatment of R/R DLBCL, little is known about its efficacy and toxicity in elderly pts. Methods: We conducted a multi-center retrospective analysis of pts age ≥ 70 years old with R/R DLBCL treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Pt demographics, tumor characteristics, CAR-T data, survival and toxicity outcomes were collected at the time of T cell infusion and follow up. Comorbidities were measured using the cumulative illness rating score (CIRS) and hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Results: A total of 77 pts were analyzed with a median age of 73 (range, 70-88); 30 (39%) pts were age ≥75. Most pts received axi-cel (n = 61, 79%). Unfavorable tumor characteristics included 27 (35%) pts with activated B-cell subtype and 12 (16%) with double/triple hit lymphomas. Median CIRS was 8 (range 0-25) and median HCT-CI was 2 (range 0-9) with significantly higher median CIRS and HCT-CI in pts age ≥75. With a median time to follow up of 5.2 months (m), median progression free survival (PFS) was 12m and median overall survival (OS) was 15.5m. There was no difference in PFS when comparing younger pts (age 70-74) to older pts (age ≥ 75), but median OS was significantly shorter for older pts (7.8m vs. not reached; hazard ratio [HR] 0.46, CI 0.21-0.98; p = 0.04). In a multivariate analysis (MVA) of PFS adjusting for baseline characteristics, HCT-CI > 2 (HR 0.23, CI 0.07-0.77; p = 0.02) and use of axi-cel (HR 0.07, CI 0.02-0.32; p = < 0.001) were associated with worse PFS. Grade 3/4 (Lee criteria) cytokine release syndrome (CRS) and CAR-related encephalopathy syndrome (CRES) were assessed in MVA adjusting for baseline characteristics. CRS was associated with CIRS ≥6 (odds ratio [OR] 3.92, CI 1.07-14.3; p = 0.002) and use of axi-cel (OR 44.9, CI 8.20-245.6; p = 0.006). CRES was associated with older age (OR 6.10, CI 1.86-20.0; p = 0.003), CIRS ≥6 (OR 3.92, CI 1.07-14.3; p = 0.04) and use of axi-cel (OR 44.9, CI 8.2-245.6; p = < 0.0001). Conclusions: Pts age ≥75 treated with CAR-T had worse OS, but comparable PFS as compared to younger pts. Validated frailty measurements (CIRS) predicted for increased CRS and CRES. Use of axi-cel was associated with worse PFS and increased toxicities in the elderly, but propensity matched scoring analysis will need to confirm this. Additional pts and longer follow up are required to validate these results.
Clinicopathologic features and outcomes of de novo transformed indolent lymphoma.
Authors: Chin Collin K , Cheah Chan , Jain Preetesh , Fowler Nathan Hale , Fayad Luis , Westin Jason , Rodriguez Maria Alma , Noorani Mansoor , Neelapu Sattva Swarup , Hagemeister Fredrick B. , Medeiros L Jeffrey , Vega Francisco , Samaniego Felipe , Flowers Christopher , Nastoupil Loretta J. 
Published: May 2020

8061 Background: Untreated transformed indolent lymphoma (unTIL) can present as a composite lymphoma (COM), 2 or more separate sites of disease with one site transformed (discordant; DIS) or following indolent lymphoma sequentially (SEQ). Current practices are guided by small retrospective studies or extrapolated from trials involving non-transformed lymphomas. Methods: 353 patients (pts) with biopsy-proven unTIL treated with curative chemoimmunotherapy between 01/2000 to 01/2019 were included (intention to treat). All indolent B-cell lymphomas (iNHL) were included except CLL/SLL. Patients with MCL and non-DLBCL transformation were excluded. Prior therapy for iNHL was not allowed except one line of non-chemotherapy-based therapy. Kaplan-Meier method was used for time-to-event analysis including progression-free (PFS) and overall survival (OS). Results: 252 (71%) pts presented with COM, 50 (14%) DIS and 51 (14%) SEQ lymphoma. The underlying iNHL was: 308 (87%) follicular lymphoma, 37 (10%) nodal MZL, 7 (2%) MALT lymphoma, and 1 (0.3%) WM. Frontline therapy (FLT) included: RCHOP for 271 (77%), DAEPOCHR for 60 (17%), clinical trial for 7 (2%), BR for 4 (1%), RHCVAD for 2 (1%), RCEOP for 2 (1%), radiation therapy for 2 (1%), RFND for (1%) 2, RCVP for 2 (1%), and rituximab only for 1 (0.3%). 9 (3%) pts had ASCT in first remission. 50 (15%) pts received maintenance rituximab (MR) with fewer cases of HGBL-DH compared to the non-MR cohort (0% v 10%). With a median follow-up of 3.4 years (range 0.1-19.1), 4-year PFS and OS rates were 59% and 88%. By univariate analysis (UVA) the underlying type of iNHL, cell-of-origin and choice of induction therapy (DAEPOCHR v RCHOP) were not associated with inferior outcomes. SEQ transformations were associated with inferior OS on UVA (P = 0.02) which was not significant on multivariable analysis (MVA) (P = 0.3). MVA identified ECOG PS > 1, B symptoms and HGBL-DH as independent prognostic factors for inferior PFS and OS. In patients who achieved PR or greater following FLT, MR was associated with improved PFS on MVA (HR 0.6, 95% CI 0.3-0.9, P = 0.04) without an OS benefit (P = 0.2). 39 (31%) pts relapsed with iNHL only (mPFS 2.4 yrs, 4-yr OS 94%) and 88 (69%) relapsed with transformed lymphoma (mPFS 1.1 yrs, 4-yr OS 69%) with no significant difference in pattern of relapse with MR (P = 0.2). Conclusions: The clinicopathologic features of unTIL are similar to those of de novo DLBCL. Escalation of therapy beyond R-CHOP may not be required in the absence of HGBL-DH. unTIL should be included in future clinical trials involving de novo DLBCL given the similar clinicopathologic features.
DREAMM-6: Safety and tolerability of belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/refractory multiple myeloma (RRMM).
Authors: Nooka Ajay K. , Stockerl-Goldstein Keith , Quach Hang , Forbes Adam , Mateos Maria-Victoria , Khot Amit , Tan Alan , Abonour Rafat , Chopra Bikramjit , Rogers Rachel , Ferron-Brady Geraldine , Davidge Jacqueline , Frey Steve , Yeakey Anne , Talekar Mala , Luptakova Katarina , Gupta Ira , Popat Rakesh 
Published: May 2020

8502 Background: Belantamab mafodotin, a B-cell maturation antigen targeting immunoconjugate, demonstrated clinically meaningful, single-agent activity in patients with heavily pre-treated RRMM refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody (DREAMM-2, NCT03525678, Lancet Oncol.2020). The multimodal mechanism of action and manageable safety profile make belantamab mafodotin a promising candidate for use in different RRMM combination regimens. Methods: DREAMM-6 (NCT03544281) is an ongoing, two-part, two-arm, study evaluating the safety, tolerability, and clinical activity of belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) and lenalidomide/dexamethasone in patients previously treated with ≥1 prior therapy line. Here, we present data for belantamab mafodotin in combination with BorDex. Part 1 (dose escalation) and Part 2 (dose expansion) evaluated belantamab mafodotin (2.5 and 3.4 mg/kg) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) in combination with BorDex. Results: As of February 6, 2020, 52 patients were enrolled: 6 patients were enrolled at 2.5 mg/kg single dose and 7 at 3.4 mg/kg single dosing in Part 1, and 45 patients in Part 2. No dose-limiting toxicities were observed. Corneal events (including keratopathy, blurred vision, and dry eye) and thrombocytopenia were the most frequently reported AEs and were clinically manageable. Conclusions: In DREAMM-6, preliminary data demonstrate that the combination of belantamab mafodotin and BorDex has an acceptable safety profile, with no new safety signals identified. Funding: GlaxoSmithKline (207497). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281 .
Updated results from BELLINI, a phase III study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.
Authors: Kumar Shaji , Harrison Simon J. , Cavo Michele , de La Rubia Javier , Popat Rakesh , Gasparetto Cristina , Hungria Vania , Salwender Hans , Suzuki Kenshi , Kim Inho , Gay Francesca , Mikala Gabor , Punnoose Elizabeth , Hong Wan-Jen , Sood Anjla , Jalaluddin Muhammad , Ross Jeremy A. , Pauff James M , Maciag Paulo Cesar , Moreau Philippe 
Published: May 2020

8509 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor. In the Phase 3 BELLINI trial, addition of Ven to bortezomib (B) + dexamethasone (d) significantly improved response rates and progression-free survival (PFS) vs placebo (Pbo) and showed significant efficacy in patients (pts) with either t(11;14) or BCL2high gene expression. Here we present updated safety and efficacy data from the prespecified second interim overall survival (OS) analysis. Methods: In this multicenter, randomized, double-blind study (NCT02755597), pts with relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo in combination with B (1.3 mg/m2) and d (20 mg). The primary endpoint was PFS; key secondary endpoints included overall response and overall survival (OS). Results: 291 pts were randomized; 194 to Ven, 97 to Pbo. Pt characteristics were well balanced among arms. In the Ven arm, median age was 66, 17% had high-risk cytogenetics, 11% had t(11;14), and 34% had BCL2high gene expression. As of 13 Sept 2019, 59 pts were still on study, 45 (23%) Ven vs 14 (14%) Pbo. At a median follow-up of 28.6 months, there were 64 (33%) deaths in the Ven arm vs 24 (25%) in Pbo. At the initial data cutoff (26 Nov 2018), PFS HR was 0.63 (0.44,0.90) and OS HR was 2.03 (1.04,3.95). Table shows updated PFS and OS. Most common treatment-emergent adverse events (TEAEs) with Ven were diarrhea (59%), nausea (37%), and constipation (35%). Most common grade 3/4 AEs (Ven/Pbo) were neutropenia (21%/8%), thrombocytopenia (15%/30%), anemia (16%/15%), diarrhea (15%/12%), and pneumonia (18%/13%). Serious AEs occurred in 54% Ven and 52% Pbo pts. 24% discontinued Ven due to AEs vs 12% Pbo. There were 14 treatment-emergent deaths in the Ven arm and 1 in Pbo. Conclusions: The addition of Ven to Bd significantly improves PFS but resulted in increased mortality vs Pbo in the total population. Greatest PFS improvement with Ven was observed in pts with t(11;14) or BCL2high gene expression, where Ven shows a favorable benefit-risk profile. The study continues for final OS analysis. Clinical trial information: NCT02755597 . [Table: see text]