Association between CAR T-cell persistence and improved response to salvage radiotherapy in patients with DLBCL

BACKGROUND AND PURPOSE: While Chimeric antigen receptor (CAR) T-cell therapy has transformed treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL), over half of patients relapse within 1 year with poor prognosis. Salvage radiotherapy (sRT) achieves high local response rates, but which subgroups benefit most and whether CAR T-cell persistence influences sRT response remains unclear. Patient/material and methods: We retrospectively analyzed DLBCL patients receiving sRT after CAR T-cell therapy at our center. CAR transgene levels were quantified by quantitative polymerase chain reaction (qPCR), and associations between CAR T-cell kinetics at relapse, sRT response, and survival were evaluated. RESULTS: CAR transgene data were available for 13 patients, (18 lesions treated with sRT). Toxicity was mild (grade ≤ 2). The local response rate was 83% (15/18 lesions). Three CAR transgene kinetic patterns were identified at relapse: increased-CAR (second increase in transgene levels, n = 4), persisted-CAR (persistence > 6 months, n = 4), and decreased-CAR (decline or absence, n = 5). Local response rates were 100% in both the increased- and persisted-CAR groups versus 57% (4/7 lesions) in the decreased-CAR group, 12-month local control rates were 83, 100, and 14%, respectively. Twelve-month overall survival was 100% in both increased-CAR and persisted-CAR groups versus 20% in the decreased-CAR group. INTERPRETATION: sRT may provide durable local control in relapsed DLBCL after CAR T-cell therapy. Persistent CAR T-cell activity at relapse may help identify patients most likely to benefit from comprehensive sRT. Given the small, heterogeneous cohort, these findings are hypothesis-generating and require validation in larger series.