Comprehensive Bridging Radiation for Limited (<5 Sites) pre-CAR T-cell Therapy non-Hodgkin Lymphoma

Summary: Chimeric antigen receptor T-cell therapy (CART) for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) results in 30% durable 5-year complete response rate1. Most post-CART relapses have a local component (>80%). Bridging radiotherapy (BRT) prior to CART achieves local control rates >80%. This study aims to report on the role of comprehensive BRT in the setting of limited (< 5 involved sites) pre-CART disease. Following IRB approval, relapsed/refractory B-cell NHL patients who received CART and had < 5 disease sites (per Ann Arbor staging) prior to leukapheresis were retrospectively studied across 3 institutions between 2018 – 2023. Patients were categorized into 2 groups based on the receipt of bridging radiotherapy (BRT vs noBRT). BRT was delivered between leukapheresis and CART infusion and was comprehensive – treating all PET-avid disease sites identified prior to leukapheresis. Patients who received bridging chemo/immunotherapy were excluded to eliminate confounding effects from other bridging treatments. Patients who received non-comprehensive (focal) BRT were excluded to better understand the impact of radiation local control in the context of limited peri-CART disease. Outcomes reported included: 1)Local relapse, defined as disease recurring at the same site(s) (with or without new sites) present on PET imaging prior to CART infusion, 2)relapse-free survival (RFS), defined from CART infusion to any disease relapse/progression, and 3)event-free survival (EFS), defined from CART infusion to any disease relapse/progression, initiation of post-CART consolidative/salvage therapy, or death. Among the 100 patients with 2 radiation-related toxicities. The median follow-up from CART infusion was 21 months. Best achieved objective response rate was 91% in the BRT group and 83% in the noBRT group (p=0.37). Sustained complete response without subsequent relapse was seen in 62% BRT and 36% noBRT patients (p=0.016). Local relapse was lower in the BRT group (15% vs. 41%, p=0.008). BRT patients had improved 2-year RFS (57% vs 47%, p=0.026) and 2-year EFS (45% vs 37%, p=0.022) compared to noBRT patients (Figure). The 2-year OS was 69% in the BRT group and 64% in the noBRT group (p=0.317). NHL patients with < 5 involved pre-CART disease sites who received comprehensive BRT had better outcomes with minimal added toxicity. Patients who did not receive BRT had higher risk of disease progression, mainly local. Comprehensive BRT improved local control and altered the pattern of relapse, which for limited pre-CART disease, translated to improvement in RFS and EFS. Omran Saifi, M.D. (Presenting Author) - Mayo Clinic; William Breen, M.D. (Co-Author) - Mayo Clinic; Scott Lester, M.D. (Co-Author) - Mayo Clinic; William Rule, M.D. (Co-Author) - Mayo Clinic; Bradley Stish, M.D. (Co-Author) - Mayo Clinic; Allison Rosenthal, M.D. (Co-Author) - Mayo Clinic; Javier Munoz, M.D. (Co-Author) - Mayo Clinic; Yi Lin, M.D. (Co-Author) - Mayo Clinic; Patrick Johnston, M.D. (Co-Author) - Mayo Clinic; Stephen Ansell, M.D. (Co-Author) - Mayo Clinic; Jonas Paludo, M.D. (Co-Author) - Mayo Clinic; Arushi Khurana, M.D. (Co-Author) - Mayo Clinic; Joce Villasboas, M.D. (Co-Author) - Mayo Clinic; Yucai Wang, M.D. (Co-Author) - Mayo Clinic; Madiha Iqbal, M.D. (Co-Author) - Mayo Clinic; Muhamad Alhaj Moustafa, M.D. (Co-Author) - Mayo Clinic; Hemant Murthy, M.D. (Co-Author) - Mayo Clinic; Mohamed Kharfan-Dabaja, M.D. (Co-Author) - Mayo Clinic; Bradford Hoppe, M.D. (Co-Author) - Mayo Clinic; Jennifer Peterson, M.D. (Co-Author) - Mayo Clinic