Outcome of Patients with Mantle Cell Lymphoma after Failure of Anti-CD19 CAR-T Cell Therapy: A Descar-T Study By Lysa Group Open Access

• Outcomes of patients with RR mantle cell lymphoma failing CAR-T cell therapy is particularly poor, without standardized salvage option.

• Bispecific antibodies appear to be a promising therapeutic option, offering durable responses compared to chemotherapy and targeted therapy.

Brexucabtagene autoleucel (brexu-cel) is the anti-CD19 CAR-T therapy approved for the treatment of relapse/refractory (RR) mantle cell lymphoma (MCL). Our study, conducted in the scope of the french DESCAR-T registry, aimed to analyze outcomes of MCL post-brexu-cel failure. In the DESCAR-T registry, 178 RR 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 (PFS2) and overall survival (OS2), according to clinical characteristics and salvage treatments. At infusion, 36% of the 61 patients had a high MIPI score, 76.2% a Ki-67 index ≥ 30%, 30.2% a TP53 mutation, and 31.6% a blastoid variant. After a median FU of 15 months post-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 to 6.7 and 9 months for those relapsing within 3-6 and after 6 months. Forty-nine patients received salvage therapy: 16 lenalidomide ± rituximab (Len/R2), 13 immunochemotherapy (ICT), 8 Bruton tyrosine kinase inhibitor ± venetoclax (BTKi/Ven), 7 a bispecific T-cell engager (TCE), 3 another targeted therapy, and 2 radiations. Overall, post-salvage response rate was 20% (9 CR, 1 PR). 1-year OS2 was 36% for patients treated with Len/R2 and ICT, 57% for TCE and 0% for others type of salvage. Notably, none of the TCE responders have relapsed to date (DOR of 100%). Our series highlights the poor outcomes of MCL patients following CAR-T failure and suggest a potential benefit of bispecific antibodies in this population.