Outcome of patients with mantle cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T study by LYSA Group.

ABSTRACT: Brexucabtagene autoleucel (brexu-cel) is the anti-CD19 chimeric antigen receptor CAR T-cell (CAR-T) therapy approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). Our study, conducted in the scope of the French DESCAR-T registry, aimed to analyze outcomes of MCL after brexu-cel failure. In the DESCAR-T registry, 178 patients with R/R MCL received brexu-cel. After a median follow-up (FU) of 14.5 months, 61 experienced failures. This study analyzes post- CAR-T failure progression-free survival (PFS2) and overall survival (OS2), according to clinical characteristics and salvage treatments. At infusion, 36% of patients had a high MCL International Prognostic Index score, 76.2% a Ki-67 index of ≥30%, 30.2% a TP53 mutation, and 31.6% a blastoid variant. After a median FU of 15 months following failure, median OS2 and PFS2 were 5.8 and 1.8 months, respectively. Patients experiencing early failure (<3 months) had a median OS2 of 1.8 months, compared with 6.7 and 9 months for those relapsing within 3 to 6 and after 6 months, respectively. Forty-nine patients received salvage therapy: 16 lenalidomide with/without rituximab (Len/R2), 13 immunochemotherapy (ICT), 8 Bruton tyrosine kinase inhibitor with/without venetoclax (BTKi/Ven), 7 bispecific T-cell engagers (TCEs), 3 another targeted therapy, and 2 received radiation. Overall, post salvage response rate (ORR) was 20%. One-year OS2 was 36% for patients treated with Len/R2 and ICT, 57% for TCEs, and 0% for other types of salvage. Notably, none of the TCE responders have relapsed to date (duration of response : 100%). Our series highlights the poor outcomes of patients with MCL after CAR-T failure and suggests a potential benefit of bispecific antibodies in this population.