One challenge of chimeric antigen receptor T-cell therapy (CAR-T) for relapsed or refractory large B-cell lymphoma (LBCL) is achieving disease control during manufacturing. We report real-word outcomes of 100 patients treated with axicabtagene ciloleucel (axi-cel, n = 50) or tisagenlecleucel (tisa-cel, n = 50) at our center. Most patients received bridging therapy (BT) with 48 undergoing radiation BT (RBT) and 32 receiving systemic BT (SBT). The best overall response rate (ORR) was 84% (78% complete response (CR)) for axi-cel and 60% (42% CR) for tisa-cel. At a median follow-up of 16 months, 12-month progression-free survival (PFS) and overall survival (OS) were 72% and 82% for axi-cel, compared to 35% and 57% for tisa-cel. By the bridging approach, 12-month PFS was 60% with RBT, 59% without BT and 35% with SBT (p = 0.06). Notably, axi-cel patients without lymphoma progression during manufacturing (n = 24) achieved 12-month PFS and OS rates of 91% and 96%, respectively. Axi-cel was associated with more cytokine release syndrome (92% vs. 66%, p = 0.003) and neurotoxicity (all-grade 56% vs. 10%, p < 0.001, grade ≥ 328% vs. 4%, p = 0.002). Multivariate analysis identified RBT as independently associated with improved PFS (HR 0.46, 95% CI 0.22–0.96). Pending prospective validation, RBT shows promise for improving CAR-T outcomes in LBCL.

Background: Allogeneic hematopoietic cell transplant (alloHCT) is a curative option for relapsed/refractory B-cell lymphomas (BCLs), but its role in the evolving field of cellular therapy is increasingly unclear as recent advances in transplant procedures have improved outcomes. Methods: This retrospective, single-center study included 55 BCL patients (large B-cell lymphoma—LBCL; indolent BCL; and mantle cell lymphoma—MCL) treated with alloHCT from 2015 to 2023 at Hôpital Maisonneuve-Rosemont. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included NRM and GVHD incidence. Results: A total of 55 patients were included (25 LBCLs, 16 indolent BCLs, 14 MCLs), and 76% of LBCLs were of indolent origin (Richter transformation, transformed follicular lymphoma). After a median follow-up of 6.1, 5.8 and 2.4 years for LBCLs, indolent BCLs and MCLs, their 5-year PFS and OS were 57.2% (IC 95%: 34.2–74.7) and 62.8% (IC 95%: 37.9–80.0), 81.2% (IC 95%: 52.5–93.5) and 93.8% (IC 95%: 63.2–99.1), and 39.0% (IC 95%: 14.3–63.3) and 68.1% (IC 95%: 35.4–86.8), respectively. The 5-year NRM was 16.9% (IC 95%: 8.2–28.3) with a relapse incidence of 23.4%. Overall/grade 3–4 acute GVHD occurred in 43.6% and 18.1% of patients. At 3 years, overall/moderate or severe chronic GVHD incidence was 49% and 34.5%. Conclusions: AlloHCT remains a potentially curative option and should be considered for fit patients with chemosensitive FL or LBCLs of indolent origin and a low comorbidity index.