Outcomes with bendamustine lymphodepletion prior to brexucabtagene autoleucel for mantle cell lymphoma

JOURNAL OF CLINICAL ONCOLOGY(2023)

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摘要
e19540 Background: 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 as well as institutional practice, we have utilized alternatives to fludarabine-based LD prior to brexu-cel, predominantly bendamustine. Bendamustine is an attractive option because it is included in the label for another anti-CD19 CAR T cell product. We report our institutional experience with bendamustine LD followed by brexu-cel. Methods: We retrospectively examined our institutional records for all patients with MCL who were treated with bendamustine LD followed by brexu-cel from 2020-2022. Progression-free survival (PFS) was analyzed with Kapalan-Meier survival analysis. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria. Results: 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. 14/16 (88%) received bridging therapy. 14/16 (88%) patients had CRS; 11/14 (79%) had grade 1-2 CRS and 3 (21%) had grade 3 or greater CRS. 5 (31%) patients had ICANS; 2 (40%) had grade 1-2 ICANS, and 3 (60%) 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. Estimated 6-month progression-free survival was 86% (95%CI: 54-96%) and 12-month progression-free survival was 63% (95%CI: 32-82). Conclusions: Bendamustine LD prior to brexu-cel for MCL is feasible, and, although these numbers are small, appears to have comparable outcomes to that reported in real world brexu-cel data (best ORR 90% with 82% CR rate, 6 month PFS estimate 69%, 12 month PFS estimate 59%; Y Wang et al. J Clin Oncol 2023) and ZUMA-2 outcomes (93% ORR with 67% CR rate, 12 month PFS estimate 61%; M Wang et al. NEJM 2020).
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关键词
bendamustine lymphodepletion,mantle cell lymphoma,brexucabtagene autoleucel
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