Introduction: Despite progress in treating LBCL, approximately 50% to 60% of pts will either not achieve a complete response (CR) or will relapse after current first- or second-line therapy. Autologous anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized the care of pts with r/r LBCL; however, patient-specific manufacturing processes and long wait times prevent their broad use and many pts who would be eligible are unable to receive therapy due to lack of accessibility. Derived from healthy donor T cells, allogeneic CAR T cells may address this bottleneck by providing pts with rapid access to a one-dose treatment, prescribed with curative intent. Phase 1 data for anti-CD19 ALLO-501 (NCT03939026) and successor, ALLO-501A (NCT04416984), which use Cellectis’ technologies, demonstrated a manageable safety profile with no dose-limiting toxicities (DLTs) and efficacy outcomes comparable to published results for autologous CAR T therapy in pts with r/r LBCL. New data document the durability of responses achieved with ALLO-501/501A following conditioning with fludarabine (F), cyclophosphamide (C), and ALLO-647 (A). Methods: In two multicenter, single-arm, open-label, phase 1 trials, autologous CAR T-naïve pts with r/r LBCL in single-dose cohorts received conditioning with F (30 mg/m2/day) and C (300 mg/m2/day) over 3 days, and A (13 mg/day over 3 days or 30 mg/day over 2 or 3 days, for total doses of 39 mg, 60 mg, or 90 mg) followed by a single dose of ALLO-501/501A (range: 40 M cells to 360 M cells). Pts in consolidation cohorts received the same conditioning over 3 days followed by a single dose of ALLO-501/501A (120 M cells). Pts without progression at Day 28 received consolidation with additional A (30 mg on Day 29) and a second cell infusion (120 M cells on Day 30). Results: As of 26 January 2023, 33 pts were treated with Alloy-manufactured product; median times from enrollment to initiation of conditioning were 2–6 days across dosing cohorts and all (100%) pts received ALLO-501/501A per specifications. Through follow-up of up to 42.7 months, no DLTs, Gr3+ cytokine-release syndrome events, or graft versus host disease occurred; Gr3+ neurologic toxicity occurred in 6.1% of patients. Overall, CR was achieved in 14 (42.4%) pts and partial response occurred in 5 (15.2%; ORR: 57.6%) pts. Of the 14 pts who achieved CR, 9 (64.3%) remained in CR at the cutoff date, with median duration of response not reached and longest response ongoing at 29.6 months; median follow-up was 17.7 months. Conclusions: ALLO-501/501A following FCA conditioning provided durable responses with a manageable safety profile in autologous CAR T-naïve pts with r/r LBCL. Durable complete remissions continue in 9 pts with the longest ongoing response at 29.6 months. These findings support broader evaluation of ALLO-501A/ALLO-647 in the ongoing, first, potentially pivotal phase 2 trial (ALPHA2) of allogeneic CAR T therapy. The research was funded by: Allogene Therapeutics Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, immunotherapy Conflicts of interests pertinent to the abstract F. L. Locke Consultant or advisory role: A2, Allogene, Amgen, Bluebird Bio, BMS/Celgene, Calibr, Caribou, Cellular Biomedicine Group, Cowen, Daiichi Sankyo, EcoR1, Emerging Therapy Solutions, GammaDelta Therapeutics, Gerson Lehrman Group (GLG), Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Sana, Takeda, Wugen, Umoja Honoraria: Aptitude Health, ASH, BioPharma Communications CARE Education, Clinical Care Options Oncology, Imedex, Society for Immunotherapy of Cancer Research funding: Kite Pharma (Institutional), Allogene (Institutional), CERo Therapeutics (Institutional), Novartis (Institutional), BlueBird Bio (Institutional), BMS (Institutional), National Cancer Institute, Leukemia and Lymphoma Society, Allogene Educational grants: A2 Bio Other remuneration: Several patents held by the institution in my name (unlicensed) in the field of cellular immunotherapy. J. Munoz Consultant or advisory role: Kyowa Kirin, ADC Therapeutics, Alexion, Bayer, Beigene, Bristol Myers Squibb, Debiopharm, Epizyme, Fosun Kite, Kite, Genmab, Innovent, Janssen, Juno/Celgene, Karyopharm, MorphoSys/Incyte, Novartis, Pfizer, Pharmacyclics/Abbvie, Servier, Seagen Honoraria: Curio, OncView, Targeted Oncology, Physicians Education Resource, Kyowa Kirin, Seattle Genetics Research funding: Bayer, Kite, Gilead, Janssen, Seagen, Merck, Millennium, Portola, Incyte, Celgene, Genentech, Pharmacyclics S. de Vos Consultant or advisory role: Beigene—Data Safety Advisory Board R. Nath Consultant or advisory role: Actinium, Incyte Honoraria: Actinium, Incyte M. Hamadani Employment or leadership position: Medical University of Wisconsin Consultant or advisory role: Incyte, MorphoSys, Kite, Genmab, SeaGen, Gamida Cell, Novartis, Legend Biotech, Kadmon, ADC Therapeutics, Omeros, Abbvie Honoraria: ADC Therapeutics, Sanofi Genzyme, AstraZeneca, BioGene Research funding: ADC Therapeutics, Takeda, Spectrum Pharmaceuticals, Astellas Pharma O. Oluwole Consultant or advisory role: Kite, Janssen, Pfizer, Novartis, Curio Science, ADC Therapeutics, TG Therapeutics, Gilead, Abbvie, Nektar Honoraria: Gilead, Pfizer Research funding: Kite, Daichi Sankyo, Allogene M. Perales Consultant or advisory role: Merck, Miltenyi Biotec, Nektar Therapeutics, Omeros, Orca Bio, Cidara Therapeutics, Sellas Life Sciences, MorphoSys, Medigene, Servier Honoraria: Bristol-Myers Squibb, Incyte, Kite, Miltenyi Biotec, Novartis, VectivBio AG, Vor Biopharma, Abbvie, Astellas, Celgene, Karyopharm, MorphoSys, Takeda, Bellicum Research funding: Incyte, Kite Other remuneration: DSMB D. Miklos Consultant or advisory role: Fosun Kite, Janssen, Adaptive Biotech, Bristol Myers Squibb, Novartis Honoraria: Fosun Kite, Janssen Research funding: Allogene Therapeutics Other remuneration: Pharmacyclics—patent & royalties P. Fisher Employment or leadership position: Allogene Therapeutics, Bristol Myers Squibb Stock ownership: Allogene Therapeutics L. Goyal Employment or leadership position: Allogene Therapeutics Stock ownership: Allogene Therapeutics L. Navale Employment or leadership position: Allogene Therapeutics Consultant or advisory role: Allogene Therapeutics, Gamida Cell, Neogene Stock ownership: Allogene Therapeutics G. Kaufman Employment or leadership position: Allogene Therapeutics Stock ownership: Allogene Therapeutics K. Kai Employment or leadership position: Allogene Therapeutics, Nektar Therapeutics Stock ownership: Allogene Therapeutics A. Balakumaran Employment or leadership position: Allogene Therapeutics Stock ownership: Allogene Therapeutics Other remuneration: Allogene Therapeutics—Patent & Royalty S. Neelapu Consultant or advisory role: Kite, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics, Bluebird Bio, Medscape, Aptitude Health, Bio Ascend Honoraria: Kite, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics, Bluebird Bio, Medscape, Bio Ascend Research funding: Kite, Merck, Bristol Myers Squibb, Celgene, Allogene, Precision Biosciences, Adicet Bio, Unum Therapeutics, Aptitude Health, Poseida, Cellectis, Karus Therapeutics, Acerta Educational grants: Kite, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics Other remuneration: Takeda—Patents & Royalties
No takes yet. Share an insight, caveat, or question.
Locke et al. (2023) studied this question.
Synapse has enriched 5 related papers. Consider them for comparative context: