Outcomes of CAR T-cells therapy in High-grade B-cell lymphomas compared to DLBCL: a weighted comparison analysis

Abstract

High-grade B-cell lymphomas [HGBL, including double-hit/triple-hit (HGBL-DH/TH) and HGBL not otherwise specified (HGBL-NOS)] have a poor prognosis upon failure of first-line therapy. Anti-CD19 chimeric antigen receptor (CAR) T-cells for third-line aggressive large B-cell lymphomas resulted in long-term remission in up to 40% of patients. This study evaluated factors that can predict outcomes in HGBL compared to Diffuse Large B-cell lymphomas (DLBCL). We assessed the predictive value of the subtype (HGBL versus DLBCL) using weighted log-rank tests and weighted Cox models, and overall survival (OS) following CAR T-cells failure. The prospective study cohort comprised 432 patients [HGBL (n=78); DLBCL (n=354)] with a median follow-up of 22.8 months for HGBL and 18 months for DLBCL. Interestingly, there was no statistically significant difference in progression-free survival (PFS) and OS between patients with HGBL-DH/TH lymphomas versus other high-grade histotypes. CAR T-cells expansion in HGBL did not correlate with response. Before weighting, a significant difference in OS was observed between HGBL versus DLBCL (24-month OS: 37% vs. 49%, p=0.0036). After weighting, the difference in 2-year OS remained significant (37% versus 44%, p=0.0343), and it was related to an inferior survival following CAR T-cells failure. The 2-year NRM and incidence of secondary malignancies were similar in HGBL and DLBCL patients (11% versus 11%, p=0.830; 6.4% versus 11.4%, p=0.844). Among patients failing CAR T-cells, the 1-year OS post failure was significantly higher in transformed than de novo DLBCL and HGBL (59% versus 32% versus 11%, <0.0004). Earlier use of CAR T-cells may improve the outcome of HGBL. NCT06339255.