Different treatment eras for relapsed and refractory primary mediastinal B-cell lymphoma patients: accessibility to CAR T cells is associated with a better prognosis in a pooled analysis of the REPRIME-FIL and the CART-SIE studies.

Abstract

Chimeric Antigen Receptor (CAR) T-cell therapy targeting CD19 has demonstrated efficacy as salvage treatment for patients with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL), however, a direct comparison between CAR T activity and other salvage treatments has not previously been performed. This study aims to compare overall survival (OS) in R/R PMBCL patients treated in different eras who reflect accessibility to CAR T-cells in R/R patient treated after 2019 and treatment with other salvage programs in the years before. We performed a pooled analysis including all pts affected by R/R PMBCL enrolled in the ongoing multicenter prospective observational study CART-SIE and in the retrospective REPRIME-FIL study. A total of 191 patients were included, 87 receiving CAR T cells and 104 treated with other salvage therapies. The 3-year OS from failure of first line treatment for the entire cohort was 62% (95% CI 55-69). The 6-months landmark analysis showed that patients treated with CAR T cells had a significantly reduced risk of death and a superior OS compared with those receiving other regimens (adjusted HR 0.34; 95%CI 0.17-0.66, p=0.001). Patients treated with CAR T cells also had superior OS compared with the subgroup of REPRIME patients who underwent ASCT (adjusted HR 0.27; 95%CI 0.13-0.66, p=0.001). Within the limitations inherent to a pooled analysis, administration of CAR T cells during salvage of R/R PMBCL patients appears to be associated with a longer OS with a risk of death approximately one-third of that observed in patients managed without CAR T.