SALVAGE RADIOTHERAPY IN RELAPSED/REFRACTORY LARGE B‐CELL LYMPHOMA AFTER CAR T‐CELL THERAPY FAILURE

Abstract

Introduction: We sought to describe our experience with salvage radiation therapy (RT) relative to other therapies in patients with relapsed/refractory large B-cell lymphoma (LBCL) post-CD19-targeted chimeric antigen receptor (CAR T)-cell therapy failure. Methods: A multi-institutional retrospective study was conducted in a database of 352 consecutive LBCL patients who received axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between 2017 and 2021. Patients who relapsed following CAR T-cell therapy and received salvage therapies (RT alone, systemic therapy alone, or combined modality therapy [CMT]) were identified and analyzed. A separate analysis was then conducted for patients who were treated with comprehensive versus focal RT. Results: A total of 120 patients with post-CAR T relapsed LBCL received salvage therapies (RT alone, 14 patients; CMT, 40 patients; systemic therapy alone, 66 patients). The median follow-up after CAR T-cell infusion was 10.2 months (interquartile range [IQR]: 5.2–20.9 months). Failure occurred in previously involved sites prior to CAR T-cell therapy in 78% of patients (n = 93). The median time from CAR T-cell therapy infusion to the start of salvage therapy was 3.4 months (IQR: 1.7–6.5 months). A total of 93 sites were irradiated among the 54 patients who received RT in the RT and CMT cohorts. The median dose/fractionation were 30 Gy (range 4–50.4 Gy) and 10 fractions (range 1–28 fractions). The 1-year local control (LC) rate for the 81 assessable sites was 84%. The median overall survival (OS) from the time of salvage therapy was not reached for the RT group, 10.5 months for the CMT group, and 6.6 months for the ST group (p = 0.4). The median OS from the start date of RT was significantly higher among patients who received comprehensive RT versus focal RT (19.1 months vs. 3.0 months, p ≤ 0.001); 26 of the 29 patients who received comprehensive RT had only a single site of disease, but survival for the 3 patients with >1 site of disease was not statistically different (p = 0.17). Receipt of bridging therapy and CAR T construct were not significantly associated with OS after CAR T infusion. On multivariate survival analysis, achieving PR or CR post-CAR T (HR = 0.5, 95% CI: 0.3–0.9, p = 0.01) was independently associated with superior OS. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, radiation therapy No conflicts of interests pertinent to the abstract.