Outcomes with bendamustine lymphodepletion and brexucabtagene autoleucel for mantle cell lymphoma

Introduction: Brexucabtagene autoleucel (brexu-cel) is approved for relapsed/refractory mantle cell lymphoma (MCL). Cyclophosphamide/fludarabine for lymphodepletion (LD) is standard LD prior to brexu-cel. Due to a recent fludarabine shortage, we have utilized alternatives to fludarabine-based LD prior to brexu-cel, primarily bendamustine. We have previously reported our institutional experience with bendamustine LD prior to another anti-CD19 CAR T cell product. Methods: We retrospectively examined all patients with MCL who were treated with bendamustine LD followed by brexu-cel at our center from 2020 to 2022. Progression-free survival (PFS) was analyzed by Kaplan-Meier survival analysis. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT consensus criteria. Results: Of 26 patients who received brexu-cel, 16 patients received bendamustine followed by brexu-cel. Median age was 65 years (range: 54–76). Median number of prior therapies was 3 (range: 3–8). All patients (100%) had received a BTK inhibitor prior to brexu-cel; 9/16 (56%) were BTKi refractory. 14/16 (88%) had received bridging therapy. 14/16 (88%) patients developed CRS; 11/14 (79%) had grade 1–2 CRS and 3 (19%) had grade 3 or greater CRS. 5 (31%) patients had ICANS; 2 (12.5%) had grade 1–2 ICANS, and 3 (19%) had grade 3 or greater ICANS. 10 (63%) patients received tocilizumab, 8 (50%) received dexamethasone, and 3 (19%) received anakinra for management of CRS and/or ICANS. Best objective response rate (ORR) was 81% with 11 (69%) patients achieving CR. Median follow-up was 13.4 months. Six month progression-free survival was 86% (95% CI: 54%–96%) and 12-month progression-free survival was 63% (95% CI: 32–82). Of 6 patients who had disease progression, two have died; median time to progression was 8.8 months. Encore Abstract - previously submitted to ASCO 2023 Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Immunotherapy Conflicts of interests pertinent to the abstract. E. A Chong Consultant or advisory role: Novartis, BMS, Beigene, Kite Research funding: Genentech J. N Gerson Research funding: LOXO D. J Landsburg Consultant or advisory role: Karyopharm, Morphosys, ADC Therapeutics, Calithera, Epizyme Research funding: Curis, Triphase S. K Barta Honoraria: Acrotech, Affimed, Daiichi Sankyo, Janssen, Kyowa Kirin J. Svoboda Consultant or advisory role: SEAGEN, Pharmacyclics, Incyte, Genmab, BMS, Atara, Astra Zeneca, Adaptive, ADCT Research funding: TG, SEAGEN, Pharmacyclics, Merck, Incyte, BMS, Astra Zeneca, Adaptive M. Ruella Other remuneration: Patent related to CAR T cells managed by the University of Pennsylvania D. L Porter Consultant or advisory role: Novartis, Kite/Gilead, Incyte, Gerson Lehrman Group, Janssen (Johnson and Johnson), Jazz, DeCART. BMS, Bluebird Bio, Angiocrine, Mirror Biologics, Capstan Therapeutics Stock ownership: Genentech, Roche (Spouse former employment) Research funding: Novartis Other remuneration: Patents, Royalties, Other Intellectual Property: Novartis, Tmunity N. V Frey Consultant or advisory role: Kite Pharmaceuticals, Sana Biotechnology, Mneumo therapeutics, Pfizer