TRANSCAR: real-world outcomes of CD19 CAR T-cell therapy in relapsed/refractory transformed indolent lymphomas

Abstract

Anti-CD19 chimeric antigen receptor (CAR) T cells have shown impressive results in the treatment of relapsed/refractory aggressive large B-cell lymphomas (LBCLs). However, the prognostic value of the LBCL histological subtype in the context of CAR T-cell therapy is unclear. Here, we report the prognostic value of transformed indolent non-Hodgkin lymphoma (TriNHL; N = 110) confirmed by an expert pathological review (LYMPHOPATH) vs de novo LBCL (N = 391) in the context of CAR T-cell therapy from 4 centers of the French DESCAR-T registry. After 1:1 propensity score matching (n = 170, 85 patients with TriNHL and 85 patients with de novo LBCL), the median follow-up was 19.4 months (95% confidence interval [CI], 12.0-25.1) for patients with TriNHL and 18.5 months (95% CI, 13.8-24.8) for patients with LBCL. The 1-year progression-free survival rate was significantly better (55.8%; 95% CI, 43.6-66.4) in the TriNHL group than in the de novo LBCL group (31.7%; 95% CI, 21.4-42.6; hazard ratio, 0.54; 95% CI, 0.36-0.82; P = .0034). The best overall response rate and complete response rate were 82.4% and 63.5%, respectively, whereas they were 63.5% and 50.6%, respectively, for the TriNHL group compared with the de novo LBCL group. The 1-year overall survival was also longer in the TriNHL group than in the de novo LBCL group (72.1%, [95% CI, 59.6-81.4] vs 50.7%, [95% CI, 38.2-62.0]; P = .031). Similar findings were found via an inverse probability weighting statistical approach. No difference was observed in terms of toxicity. In conclusion, our matched-comparison study revealed a greater efficacy of CAR T-cell therapy, with a toxicity profile for patients with TriNHL comparable with that for patients with LBCL.