Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR Tcell therapy

Abstract

Despite the success of CAR T-cell therapy in patients with relapsed/refractory large- B cell lymphoma (LBCL), there is a need for effective salvage strategies post-CD19-targeted chimeric antigen receptor (CAR T)-cell therapy failure. We conducted a multi-institutional retrospective study of patients who relapsed following CAR T-cell therapy [axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel)] and received salvage therapies [RT alone, systemic therapy alone, or combined modality therapy (CMT)]. A total of 120 patients with post-CAR T relapsed LBCL received salvage therapies (RT alone, 25 patients; CMT, 15 patients; systemic therapy alone, 80 patients). The median follow-up from 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). A total of 93 sites were irradiated in 54 patients who received any salvage RT post-CAR T failure. 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%. On univariate analysis, the median OS from the start date of RT was significantly higher among patients who received comprehensive RT vs focal RT (19.1 months vs. 3.0 months, p=<0.001). Twenty-three of 29 patients who received comprehensive RT had limited-stage disease. Among these, there was no difference in median OS among the patients who received RT alone vs. those who received RT followed by additional therapies (log-rank p= 0.2). 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. Our findings suggest that RT can provide local control for LBCL relapsed post-CAR-T cell therapy, particularly in patients with limited-stage relapsed disease treated with comprehensive RT.