Multicenter experience with radiotherapy for relapse after chimeric antigen receptor T cell therapy in non‐Hodgkin lymphoma

Introduction: Approximately half of patients relapse following chimeric antigen receptor T-cell therapies (CAR T), a challenging clinical scenario without established treatment paradigms. Salvage radiotherapy (SRT) may be an important strategy for this population with rapidly growing, often chemotherapy-refractory disease. Limited data are available regarding SRT utilization and outcomes. Methods: We reviewed all patients with Non-Hodgkin Lymphoma treated with SRT for any intent post CAR T from 2016 to 2022 at four US cancer centers. Comprehensive SRT was defined as including all sites with PET avidity > liver max. Failure sites were classified as pre-existing (present pre SRT) versus new, and as in field, marginal (within 1 cm of), or distant with respect to SRT prescription dose region. Toxicities were graded by CTCAE v5.0. Event free and overall survival (EFS/OS) were measured from SRT start by Kaplan Meier. EFS was defined as freedom from progression, initiation of subsequent therapy, or death. Clinicodemographic associations with outcomes were assessed by Cox univariate proportional hazards. Results: 121 patients with diffuse large B cell lymphoma (DLBCL; n = 110), mantle cell lymphoma (n = 8), and primary mediastinal B cell lymphoma (n = 3) were included. Patients received axicabtagene (n = 62), tisagenlecleucel (n = 27), lisocabtagene (n = 17), experimental CAR T (n = 12), and brexucabtagene (n = 3). For 49%, SRT was the first post-CAR T therapy. SRT indications included palliation (n = 72), consolidation (n = 5), bridging to allogeneic transplant (allo; n = 5) or 2nd CAR T (n = 3), and other (n = 33). At SRT, 29 (24%) had localized disease of which 28 were treated comprehensively; overall 37% of SRT was comprehensive. Median dose was 30 Gy (4–50.4). 27% received concurrent systemic therapy. SRT was well tolerated: 8% (n = 10) had ≥ grade 2 (G2) acute adverse events (G3 = 1, no G4/5). Objective response rate was 74% (41% complete) within the SRT field and 38% (22% complete), overall. With a median follow up of 6 mo, 78 patients (64%) progressed. First failure sites were 64% pre-existing/mixed and 38% in field/marginal. For DLBCL patients, median EFS was 4.2 mo in limited stage and 1.2 mo in advanced (p < 0.001). Median OS was 59.6 mo and 3.4 mo in localized and advanced DLBCL relapse (p < 0.001). Median OS for RT as bridging to allo/CAR T, consolidation, and palliation was unreached, 6.7 mo, and 3.0 mo (p < 0.001). Localized relapse and receipt of comprehensive SRT were associated with improved EFS (p < 0.001) while primary refractory disease to CAR T (p = 0.02), elevated LDH pre SRT (p = 0.02), and SRT for palliation (p = 0.03) or for ≥2ndsalvage post CAR T (0.04) were associated with shorter EFS. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Radiation Therapy Conflicts of interests pertinent to the abstract. C. Ladbury Research funding: Reflexion G. Shah Consultant or advisory role: ArcellX Research funding: Janssen, Amgen, Beyond Spring, BMS M. D. Jain Consultant or advisory role: Kite/Gilead, Novartis, BMS, MyeloidTx Research funding: Kite/Gilead, Incyte S. Dandapani Research funding: Reflexion, Bayer B. S. Imber Honoraria: GT Medical Technologies Inc.