Enhancing CAR-T Efficacy in Large B-Cell Lymphoma with Radiation Bridging Therapy: A Real-World Single-Center Experience.

Abstract

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.