Pre–CAR-T B-cell–directed immunotherapy exposure and outcomes after CD19 CAR-T for large B-cell lymphoma: An EBMT registry analysis

CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) is standard-of-care second-line treatment for relapsed or refractory large B-cell lymphoma (LBCL) [ 1 , 2 , 3 ]. Bispecific antibodies (BSA) and polatuzumab vedotin (pola) are increasingly used prior to CAR-T, but the impact of such exposure, particularly before leukapheresis, when therapies may affect T-cell collection and fitness, remains unclear [ 4 , 5 , 6 , 7 ]. We identified 1158 patients from 38 centers undergoing licensed CD19-directed CAR-T therapy (axicabtagene ciloleucel [axi-cel] or tisagenlecleucel [tisa-cel]) between January 2018 and July 2023 from the European Society for Blood and Marrow Transplantation (EBMT) registry (Table S1 , Fig. S1 ). Pre–CAR-T B-cell–directed immunotherapy (BCDI) was defined as exposure to bispecific antibodies, polatuzumab-based regimens, or other B-cell–directed agents excluding rituximab. Overall survival (OS) was the primary endpoint and outcomes were analyzed using multivariable Cox regression models adjusted for clinically relevant covariates.