TRANSCAR: Real-World outcomes of CD19CAR T Cell Therapy in relapsed/refractory transformed indolent lymphomas

• The outcome of relapsed/refractory (R/R)-transformed indolent non-Hodgkin lymphoma is better than that of R/R de novo large B-cell lymphoma.

• The toxicity profile of CAR T cells in R/R-transformed indolent non-Hodgkin lymphoma is acceptable.

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 pathologic 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 TriNHL patients and 85 de novo LBCL patients), the median follow-up was 19.4 months (95% CI, 12.0-25.1) for TriNHL patients and 18.5 months (95% CI, 13.8-24.8) for LBCL patients. 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=0.0034). The best overall response rate/complete response rate was 82.4%/63.5%, whereas it was 63.5%/50.6% 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=0.031). 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 comparable toxicity profile for TriNHL patients than for LBCL patients.