bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1/2 study of anbalcabtagene autoleucel, novel anti-CD19 CAR-T cell therapy with dual silencing of PD-1 and TIGIT in relapsed or refractory large B-cell lymphoma.
Authors: Kim Won Seog , Kim Seok Jin , Yoon Sangeun , Kim Jong Ran 
Published: June 2022

7522 Background: Anbal-cel is a novel 2nd generation autologous CD19 CAR-T cell therapy which has been knock-downed for PD-1 and TIGIT using OVIS platform. Anbal-cel demonstrated the eradication of CD19 positive tumor cells in vitro and in vivo better than conventional CD19 CAR-T cells. The knock-down of PD-1 and TIGIT at CD19 CAR-T cells exerts the superior T-cell functionality by delaying the exhaustion of CAR-T cells. Methods: This phase 1 dose escalation part (NCT04836507) was evaluated the safety and preliminary efficacy in patients with r/r LBCL. Anbal-cel was manufactured at GMP facility with fresh leukapheresis product. Patient was administered as a single intravenous dose at dose level 1 (2x105 cells/kg), DL2 (7x105 cells/kg) or DL3 (2x106 cells/kg). Lymphodepletion with cyclophosphamide (500mg/m2) and fludarabine (30mg/m2) was performed for 3 days prior to Anbal-cel infusion. Results: As of Jan 17 2022, 9 patients with r/r DLBCL were infused with Anbal-cel; 4pts at DL1, 3pts at DL2 and 2pts at DL2. Median age was 54 (range 26-71); all patients received 2 or more prior lines of therapy and 44% (4/9) received ≥4 prior line of treatment before the study. 78% (7/9) patients were refractory to their last treatment. 67% (6/9) of patients were at IPI 3-4 and 44% (4/9) of patients had bulky disease. No patient experienced DLT during the study. Of the 9 patients, 5 (56%) experienced CRS; 4 (44%) were grade 1 or 2 and one patient experienced grade 3 CRS. Median time to onset of CRS was 7 days (range, 1-16) with median duration of 4 days (range, 0-18). One patient dosed at DL3 experienced grade 2 ICANS, time to onset of ICANS was 7 days and lasted for 13 days. This patient had prior CNS involvement history before the study. Most commonly reported grade 3/4 AEs were neutrophil count decrease (6/9, 67%), anemia (5/9, 56%), thrombocytopenia (2/9, 22%), platelet count decrease (2/9, 22%) and no infection was reported. Complete response rate (CRR) was 78% and complete responses were observed at the lowest dose level and from patients expressing less than 10% CD19 at IHC; 3 complete responses (CR) at DL1, 2 CRs at DL2 & DL3 respectively. Dose-dependent CRC01 expansion was observed; median Tmax was 15.4, 15.8, 11.0 days at DL1, DL2 & DL3 each; median Cmax was 18,003, 30,103, 53,688 copies/ug gDNA at DL1, DL2 & DL3 each; median AUC0-28day was 679,125, 1,110,108, 2,852,235 copies/ug gDNA at DL1, DL2 & DL3 respectively. Conclusions: Anbal-cel demonstrated promising efficacy and tolerable safety profile in this dose escalation study. Based on this phase 1 study, phase 2 patient enrollment will be commenced in Mar 2022 to evaluate the response rate, duration of response of CRC01 as well as safety. In addition, various biomarker studies are planned to investigate the differential mode of action of Anbal-cel during phase 2 study. Clinical trial information: NCT04836507.
Demographics and treatment outcomes in patients with EBV+ PTLD treated with off-the-shelf EBV-specific CTL under an ongoing expanded access program in Europe: First analyses.
Authors: Choquet Sylvain , Chaganti Sridhar , Uttenthal Ben , Comoli Patrizia , Trappe Ralf Ulrich , Friedetzky Anke , Xing Baodong , Li Xiaoming , Polak Tobias Boy , Gamelin Laurence , Terwey Jan-Henrik , Dierickx Daan 
Published: June 2022

7530 Background: Patients undergoing allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT) are at risk of developing Epstein–Barr virus driven post-transplant lymphoproliferative disorder (EBV+ PTLD), a rare hematologic malignancy, which is often aggressive and life-threatening. Patients with relapsed or refractory (r/r) EBV+ PTLD have few treatment options with poor outcomes, demonstrating a clear unmet medical need. Tabelecleucel is an investigational, off-the-shelf, allogeneic EBV-specific T-cell immunotherapy being studied in patients with serious EBV+ diseases (NCT04554914 & NCT03394365) that has demonstrated clinical benefit and favorable safety profile in the treatment of EBV+ PTLD after failure of rituximab (R) ± chemotherapy (Prockop, EBMT 2021, ATC 2021, ASH 2021). Methods: Atara Biotherapeutics supports an ongoing expanded access program (EAP) in Europe for patients with EBV+ diseases who have no other treatment options. Here we report demographics, efficacy and safety results of r/r EBV+ PTLD patients following SOT or HCT who presented between Jul 2020 and Nov 2021 and consented to research. Results: A total of 48 EAP requests from 9 countries for patients with EBV+ diseases were received. Twenty-two patients from 7 countries consented to this research: 16 EBV+ PTLD and 6 EBV+ non-PTLD. Of the 16 PTLD patients 15 received at least one dose of tabelecleucel. Overall, 9 out of 15 (60%) patients achieved a response as assessed by the treating physician, with 6 complete responses and 3 partial responses. Eight out of nine responses were seen after the first cycle. No adverse events were reported as related to tabelecleucel by the treating physician. Conclusions: The successful execution of this European EAP demonstrates the feasibility to deliver an off-the-shelf allogeneic EBV+ T-cell therapy in time-sensitive clinical situations when no other treatment options exist. These data show clinically meaningful outcomes for patients with r/r EBV+PTLD post-SOT or post-HCT treated with tabelecleucel consistent with previously reported favorable safety and efficacy profile (Prockop, ASH 2021).[Table: see text]
Acalabrutinib versus rituximab plus idelalisib or bendamustine in relapsed/refractory chronic lymphocytic leukemia: ASCEND results at 4 years of follow-up.
Authors: Jurczak Wojciech , Pluta Andrzej , Wach Malgorzata , Lysak Daniel , Simkovic Martin , Kriachok Iryna , Illés Árpád , De La Serna Javier , Dolan Sean , Campbell Philip , Musuraca Gerardo , Jacob Abraham , Avery Eric Joseph , Lee Jae Hoon , Usenko Ganna , Wang Min Hui , Yu Ting , Ghia Paolo 
Published: June 2022

7538 Background: Acalabrutinib (acala) is a next-generation, highly selective, covalent Bruton tyrosine kinase (BTK) inhibitor approved for patients (pts) with chronic lymphocytic leukemia (CLL). In the primary analysis of ASCEND (median follow-up 16.1 mo), acala showed superior efficacy with an acceptable tolerability profile vs idelalisib (Id) plus rituximab (R) (IdR) or bendamustine (B) plus R (BR) in pts with relapsed/refractory (R/R) CLL (Ghia et al. J Clin Oncol. 2020;38:2849-2861). We report the results of the ASCEND study at ~4 years of follow-up. Methods: In this multicenter, randomized, open-label, phase 3 study (NCT02970318), pts with R/R CLL received oral (PO) acala 100 mg BID until progression or unacceptable toxicity or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or unacceptable toxicity; R: 375 mg/m2 x1 then 500 mg/m2 IV [8 total infusions]) or BR (B: 70 mg/m2 IV; R: 375 mg/m2 x1 then 500 mg/m2 IV [6 cycles]). Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed. Results: A total of 310 pts (acala, n=155; IdR, n=119; BR, n=36) were randomized (median age 67 y; del(17p) 15%, unmutated IGHV 74%, Rai stage 3/4 42%). At median follow-up of 46.5 mo (acala) and 45.3 mo (IdR/BR), acala significantly prolonged INV-assessed PFS vs IdR/BR (median not reached [NR] vs 16.8 mo; P<0.0001); 42-mo PFS rates were 62% for acala vs 19% for IdR/BR. In pts with del(17p), median PFS was NR (acala) vs 13.8 mo (IdR/BR; P<0.0001). In pts with unmutated IGHV, median PFS was NR (acala) vs 16.2 mo (IdR/BR; P<0.0001). Median OS was NR in both arms; 42-mo OS rates were 78% (acala) vs 65% (IdR/BR). ORR was 83% (acala) vs 84% (IdR/BR) (ORR + partial response with lymphocytosis: 92% [acala] vs 88% [IdR/BR]). AEs led to drug discontinuation in 23% of acala, 67% of IdR, and 17% of BR pts. Events of clinical interest (acala vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), and grade ≥3 infections (29% vs 29%). Conclusions: At ~4 years of follow-up, acala maintained efficacy compared with standard-of-care regimens and a consistent tolerability profile in R/R CLL. Clinical trial information: NCT02970318. [Table: see text]
Analysis of peripheral neuropathy (PN) using clinician- and patient-reported outcomes (ClinRO and PRO) in the POLARIX study.
Authors: Trneny Marek , Fogliatto Laura , Gardner Faithlore Patrice , Flinn Ian W. , Larouche Jean-Francois , Haioun Corinne , Canales Albendea Miguel Angel , Goto Hideki , Hajek Roman , Salles Gilles A. , Qiu Jiaheng , Campinha-Bacote Avrita , Yan Mark , Kothari Rucha , Man Gabriel , Sahin Deniz , Hirata Jamie , Lee Calvin , Tilly Herve , Flowers Christopher 
Published: June 2022

7561 Background: PN is an identified risk of anti-microtubule agents, including polatuzumab vedotin and vincristine. POLARIX (NCT03274492), a Phase III randomized, double-blind, placebo-controlled study comparing Pola-R-CHP with R-CHOP, demonstrated improved progression-free survival (PFS) with Pola-R-CHP (Tilly et al. NEJM 2022). Here, we evaluate the impact of Pola-R-CHP vs R-CHOP on PN using ClinRO and PRO data. Methods: Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) received Pola-R-CHP or R-CHOP. ClinRO data were based on PN grading according to the NCI CTCAE v4.0. PRO data were generated from assessment of patient-reported PN symptoms at baseline and Day 1 of each cycle using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity (FACT-GOG/NTX) subscale, ranging from 0–44, with higher scores representing lower levels of PN (minimal clinically important difference: 1.38–3.68 [Cheng et al. Health Qual Life Outcomes 2020]). Results: At baseline, ClinRO and PRO symptom scores showed low PN burden (Table). Overall incidence of PN was comparable between treatment arms (Pola-R-CHP: 52.9%; R-CHOP: 53.9%); most events were grade 1, and incidence of grade 2 (Pola-R-CHP: 12.2%; R-CHOP: 15.5%) and grade 3 (Pola-R-CHP: 1.6%; R-CHOP: 1.1%) events were comparable between treatment arms. FACT-GOG/NTX survey completion was high in both arms (96% at baseline; >80% at other timepoints). When evaluated by cycle, ClinRO and PRO demonstrated that more patients experienced earlier onset PN with R-CHOP than with Pola-R-CHP (Table), with ̃10% more R-CHOP- than Pola-R-CHP-treated patients having clinician-reported PN in Cycle (C) 2–5, and a ̃+1-point difference (i.e. fewer symptoms) in PRO symptom scores in C3–6 with Pola-R-CHP vs R-CHOP; by C8+, and during follow up, rates and symptoms of PN were similar. PN symptoms resulted in fewer dose reductions (3.9% vs 8.2%) and drug discontinuations (0.7% vs 2.1%) with Pola-R-CHP vs R-CHOP. Duration of PN was similar for both treatments. Conclusions: In the POLARIX study, Pola-R-CHP did not result in different rates or severity of PN vs R-CHOP. According to ClinRO and PRO data, PN occurred later following initial exposure to Pola-R-CHP than to R-CHOP, and there were fewer dose modifications with Pola-R-CHP than with R-CHOP. Overall, the risk of PN was manageable. Clinical trial information: NCT03274492. [Table: see text]
Safety and clinical activity of belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-6 arm-A interim analysis.
Authors: Quach Hang , Gironella Mercedes , Lee Cindy , Popat Rakesh , Cannell Paul , Kasinathan Ravi , Chopra Bikramjit , Rogers Rachel , Ferron-Brady Geraldine , Shafi-Harji Seema , Patel Nashita , Opalinska Joanna , Gupta Ira V. , Augustson Bradley 
Published: June 2022

8017 Background: Belantamab mafodotin (belamaf; BLENREP) is a B-cell maturation antigen-targeting antibody–drug conjugate approved for patients (pts) with RRMM as monotherapy at 2.5 mg/kg Q3W. Preclinical data demonstrate synergy between belamaf and lenalidomide (Len), suggesting added benefit when combined with standard of care such as Len + dexamethasone (Dex). DREAMM-6 (NCT03544281) Arm A is evaluating belamaf in combination with LenDex in pts with RRMM. Methods: This ongoing, two-part, two-arm, open-label study included pts with RMMM previously treated with ≥1 line of therapy (LOT). Pts received 4 belamaf doses/schedules (1.9 mg/kg Q8W or Q4W; 2.5 mg/kg Q4W or Q4W SPLIT dose [50% on Days (D)1, 8] IV) in combination with Len (20 mg PO D1–21) and Dex (20 mg PO/IV D1, 8, 15, 22). Primary objectives were safety (including treatment-related [TR]AEs related to the combination belamaf and LenDex), tolerability, and efficacy (including overall response rate [ORR] defined as ≥partial response). Results: As of this interim analysis (data cut: July 23, 2021), 45 pts received ≥1 dose (12 at 1.9 mg/kg Q8W; 4 at 1.9 mg/kg Q4W; 16 at 2.5 mg/kg Q4W; 13 at 2.5 mg/kg Q4W SPLIT). Across cohorts, the median age was 68 y (range: 36–80). Thirteen pts (29%) had high-risk cytogenetics and 6 (13%) had extramedullary disease. Median prior LOT was 3 (range: 1–11) and 26 (58%) had prior Len treatment. The median duration of follow-up and ORR ranged across cohorts (Table). The median duration of response was only reached in the 1.9 mg/kg Q4W cohort (11.1 mo [95% CI: 3.7–not reached [NR]). At the time of data cut, median progression-free survival was not reached in the 1.9 mg/kg Q8W or 2.5 mg/kg Q4W cohorts. Gr ≥3 TRAEs occurred in 42–85%. Gr ≥3 keratopathy occurred in 0 pts in 1.9 mg/kg Q8W, 1 pt (25%) in 1.9 mg/kg Q4W, 8 pts (50%) in 2.5 mg/kg Q4W, and 6 pts (46%) in 2.5 mg/kg Q4W SPLIT cohorts. Conclusions: Belamaf + LenDex had a tolerable safety profile, with no new safety signals identified in pts with RRMM. AEs, including keratopathy, were common but manageable with dose modifications. Encouraging clinical activity is observed with this combination in pts with RRMM. Follow-up/correlative studies are ongoing. Funding: GSK (Study 207497); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281. [Table: see text]
Synergistic effects of low-dose belantamab mafodotin in combination with a gamma-secretase inhibitor (nirogacestat) in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-5 study.
Authors: Lonial Sagar , Grosicki Sebastian , Hus Marek , Song Kevin W. , Facon Thierry , Callander Natalie Scott , Ribrag Vincent , Uttervall Katarina , Quach Hang , Vorobyev Vladimir I. , Min Chang Ki , Cheng Shinta , Smith L. Mary , Yu Jing , Collingwood Therese , Holkova Beata , Kremer Brandon , Gupta Ira , Richardson Paul G. , Minnema Monique C. 
Published: June 2022

8019 Background: Preclinical data demonstrate that nirogacestat, a gamma-secretase inhibitor, may increase cell-surface levels of a B-cell maturation antigen (BCMA) and reduce soluble BCMA levels, which could enhance anti-BCMA agent activity in multiple myeloma. In the DREAMM-5 (NCT04126200) Phase I/II platform trial belantamab mafodotin (belamaf; BLENREP), a BCMA-targeting antibody-drug conjugate, is being evaluated in combination with nirogacestat to determine if the combination can result in similar efficacy and an improved ocular safety profile compared to the currently approved belamaf schedule (single agent dose 2.5 mg/kg Q3W) in patients with RRMM which showed a 31% overall response rate (ORR) and 44.5% Gr3/4 keratopathy (BLENREP US prescribing information). Methods: This cohort within the DREAMM-5 nirogacestat combination sub-study has a sequential dose-exploration (DE) phase evaluating 0.95 mg/kg Q3W belamaf with 100 mg BID nirogacestat continuously, followed by a randomized cohort expansion (CE) comparing the combination to a belamaf 2.5 mg/kg Q3W arm. Results: Preliminary results from the 10 patients (pts) in the DE cohort with low-dose belamaf + nirogacestat are presented in this abstract. Pts had a median (range) of 4.5 (3–10) prior lines of therapy. At time of data cut-off (Nov 15, 2021), pts received a median (range) of 7 cycles (1–26). The ORR was 60% (n=6/10) and 20% (n=2) achieved a very good partial response (Table). The key emergent adverse events (AEs) included ocular events (n=7 [70%]; ≥Grade [Gr] 3, n=2 [20%] of which Gr 3 keratopathy was reported in 1 pt [10%]), diarrhea (n=7 [70%]; Gr 3, n=1 [10%]) and hypophosphatemia (n=7 [70%]; Gr 3, n=1, [10%]). There were 2 Grade 5 AEs, neither of which were related to study treatment. No pt permanently discontinued study due to treatment related AEs. Conclusions: Encouraging clinical activity and a manageable safety profile is observed with low dose belamaf (0.95 mg/kg Q3W) + nirogacestat (100 mg BID continuously) in pts with RRMM. This ongoing sub-study is actively recruiting patients and will continue to evaluate belamaf + nirogacestat efficacy and safety. Updated results will be reported at the congress. Funding: GSK (208887); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04126200. [Table: see text]
Health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) receiving real-life current standard of care (SOC) in the LocoMMotion study.
Authors: Delforge Michel , Moreau Philippe , Einsele Hermann , De Stefano Valerio , Lindsey-Hill Joanne , Vincent Laure , Mangiacavalli Silvia , Perrot Aurore , Ocio Enrique , ten Seldam Silene , in ’t Groen-Damen Ester , Semerjian Maria , Strulev Vadim , Schecter Jordan Mark , Roccia Tito , Gries Katharine S. , Nesheiwat Tonia , Wapenaar Robert , Mateos Maria-Victoria , Weisel Katja 
Published: June 2022

8030 Background: Evaluation of patient (pt)-reported outcomes provides insight into how real-life SOC treatments (tx) affect HRQoL for pts with RRMM. LocoMMotion (NCT04035226) is the first prospective, multinational study of real-life SOC in triple-class exposed pts with RRMM. Here, we present measures of symptoms, functioning, and overall HRQoL. Methods: LocoMMotion is a prospective, noninterventional study across 76 sites (63 European; 13 US). Pts had received ≥3 prior lines of therapy (LOT) or were refractory to PI and IMiD; received PI, IMiD, and anti-CD38 mAb; and had disease progression during/after last LOT. Real-life SOC tx were defined as those used in local clinical practice. The questionnaires were EORTC QLQ-C30, 4 single items from EORTC QLQ-MY20, and EQ 5D-5L. HRQoL was assessed at baseline (BL), day 1 of each tx cycle, end of tx visit, and during the follow-up period (every 4 weeks). Improvement compared to BL health status was evaluated using established thresholds. Within-group change was assessed using mixed models for repeated measures. Results: Questionnaire completion for pts in the LocoMMotion study (N=248; 54.4% male; median age 68 yrs; median 4.0 [range, 1–20] cycles of SOC) was 75.6% during SOC tx. Most pts did not achieve meaningful improvement in PRO scores, defined by a literature-based minimally important difference of 10 points in mean score. This was most pronounced in pain symptoms (62% of pts had no meaningful improvement during the first 3 months of tx; 55% had no improvement during full tx duration). For the overall population, the least square (LS) mean changes from BL during SOC tx and subsequent LOT are described (Table). Pts who achieved very good partial response and better during SOC tx had greater improvement in PRO scores, including in LS mean change for pain score (-14.9 [95% confidence interval (CI): -22.9, -7.0]). Conclusions: In this first prospective study of real-life current SOC in triple-class exposed pts, limited gains in HRQoL were reported, most notably in pain symptoms. There is an urgent need for effective therapies that can help pts achieve deep responses and delay disease progression, as these are associated with improved HRQoL. Clinical trial information: NCT04035226. [Table: see text]
Updated survival with extended follow-up on patients with newly diagnosed multiple myeloma treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy and a risk-stratified maintenance approach.
Authors: Parikh Rujul H , Hofmeister Craig C. , Almaula Dhwani , Heffner Leonard T. , Gupta Vikas Anand , Boise Lawrence , Kaufman Jonathan L. , Dhodapkar Madhav V. , Lonial Sagar , Nooka Ajay K. , Joseph Nisha 
Published: June 2022

8061 Background: Lenalidomide, bortezomib, and dexamethasone (RVD) has been established as an effective and well-tolerated induction regimen in patients with newly diagnosed myeloma (NDMM). We have previously published a retrospective analysis of 1000 patients treated with RVD and risk-stratified maintenance therapy showing a median PFS of 65 months and median OS of 126 months for the entire cohort (Joseph et al, JCO 2020). This data has served as an important benchmark for evaluating upfront treatment strategies in NDMM. Here, we present updated survival data with extended follow up on this patient population treated at the Winship Cancer Institute of Emory University. Methods: From January 2007 to August 2016, 1000 consecutive newly diagnosed myeloma patients treated with RVD induction therapy (R-25 mg/day on days 1-14, V-1.3 mg/m2 on days 1,4,8,11 and D-40 mg once/twice weekly as tolerated) were identified. Demographics, clinical characteristics, and outcomes data for the patients were obtained from our institutional review board-approved myeloma database. Responses were evaluated per IMWG Uniform Response Criteria. Results: The median age of this cohort was 61 (range 16-83). Other notable patient characteristics include: M/F 54.6%/45.4%, W/AA 61.8%/35.9%; ISS I/II/III 45.8%/30.8%/23.4%. R-ISS I/II/III 39.9%/48.7%/11.5%; Isotype IgG/IgA/FLC 59.2%/19.0%/15.7%; standard risk(SR)/high risk (HR) 71.2%/15.8%.. High risk disease was defined as the presence of t(4;14), t(14;16), del(17p), and/or complex karyotype by conventional metaphase cytogenetics. 81.8% of patients underwent ASCT, with 16.8% having deferred ASCT. 75.3% of patients were initiated on maintenance therapy. With a median follow up of 88.4 months, the median PFS for the entire cohort was 68.7 months (95% CI 61.8-75.5) and the median OS was 128.9 months. The median PFS for HR patients was 42.4 months (95% CI 35.7-48.9), and the median PFS for SR patients was 80.3 months (95% CI 72.8-87.8). The median OS for SR patients was not reached, and for HR patients was 86.6 months (95% CI 70.1-103.1). Conclusions: Updated analysis with long-term follow up of this database of 1000 NDMM patients treated with RVD continues to demonstrate that, in combination with a risk-stratified maintenance strategy, RVD delivers durable remissions and impressive long-term outcomes. This study remains the largest cohort of patients treated with RVD reported to date, and continues to show the efficacy of this upfront treatment approach in newly diagnosed myeloma.