Outcomes of patients over 70 years treated with brexu-cel for R/R mantle cell lymphoma: a study from the CTIWP of EBMT

ABSTRACT: Mantle cell lymphoma (MCL) predominantly affects older adults, and treatment options for relapsed/refractory (R/R) disease remain limited. Brexucabtagene autoleucel (brexu-cel) has demonstrated high efficacy in R/R MCL, but data in older adult populations are scarce. This retrospective, real-world analysis evaluated patients aged ≥70 years with R/R MCL treated with brexu-cel and reported to the EBMT registry between 2020 and 2024. A total of 233 patients from 96 centers across 13 countries were included (median age at infusion, 74.6 years; 44% >75 years). Most had Eastern Cooperative Oncology Group (ECOG) 0 to 1 (89%) and were heavily pretreated; 62% had prior Bruton tyrosine kinase inhibitor exposure. At day +100, the best overall response was complete remission in 78% and partial remission in 13%. At 30 days, the cumulative incidence of any-grade cytokine release syndrome was 80% (grade ≥3, 9%) and immune effector cell-associated neurotoxicity syndrome was 57% (grade ≥3, 22%). At 1 year, overall survival (OS) was 74%; progression-free survival (PFS), 62%; relapse/progression incidence, 25%; and nonrelapse mortality (NRM), 13%. Patients aged >75 years had outcomes comparable with those aged 70 to 75 years. In multivariable analysis, ECOG ≥2 remained the strongest predictor of inferior OS (hazard ratio [HR], 4.50; P< .001) and PFS (HR, 3.10; P< .001), whereas age was not independently associated with outcomes. Brexu-cel is effective in patients aged ≥70 years with R/R MCL, achieving high remission rates and meaningful survival, despite a relatively high incidence of NRM. Functional status, rather than age, should guide eligibility.