Salvage radiotherapy for relapsed/refractory non‐Hodgkin lymphoma following CD19 chimeric antigen receptor T-cell (CART) therapy

Abstract

CD19-targeting chimeric antigen receptor T-cell (CART) therapy is a promising treatment for relapsed/refractory non-Hodgkin lymphoma, but most patients experience post-CART progression. We describe our institutional experience of salvage radiotherapy (SRT) in this setting. Of 94 patients who received CART therapy from 2018 to 2020, 21 received SRT for post-CART progression. Patients were divided into two groups: locoregional disease (n=9 [43%], all disease encompassable within an RT field) and advanced disease (n=12 [57%]). Patterns of failure, progression-free survival (PFS), overall survival (OS), and toxicity were assessed. Median time from CART infusion to SRT was 4.0months (range, 0.6-11.5months). In the locoregional disease group, 8/9 patients (89%) were treated with comprehensive SRT to a median dose of 37.5Gy in a median of 15 fractions. In the advanced disease group, all patients (n=12) were treated with focal SRT to a median dose of 20.8Gy in a median of 5 fractions. Median follow-up post-SRT was 15.2months. In-field response was observed in 8/9 (89%) in the locoregional disease and 8/9 (89%) evaluable patients in the advanced disease groups. 17/18 evaluable patients (94%) patients experienced post-SRT progression, all with a distant component. Median OS was 7.4months; 21months for locoregional disease versus 2.4months for advanced disease (p=0.0002). Median PFS was 1.1month, and similarly poor regardless of group. No grade≥3 toxicities occurred. SRT post-CART therapy appears safe with encouraging in-field response but high rates of out-of-field progression, even for those presenting with locoregional disease, highlighting the need for integration of novel systemic agents.