Impact of CD5 expression on outcomes for chimeric antigen receptor-T cell therapy in relapsed and refractory diffuse large B-cell lymphoma.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has become the standard of care for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). However, CD5 expression is known to be associated with an aggressive phenotype in DLBCL, and its impact on outcomes after CAR-T cell therapy remains unknown. To investigate this clinical issue, 106 patients treated with CAR-T cell therapy using either tisagenlecleucel, lisocabtagene maraleucel or axicabtagene ciloleucel for r/r DLBCL at our institution were retrospectively analyzed. Twenty-six (25%) patients were classified as CD5 positive, and 76 (72%) patients as CD5 negative. Response to CAR-T cell therapy was poorer for evaluable patients in the CD5-positive group (complete response [CR], 42%; overall response [OR], 54%) than for evaluable patients in the CD5-negative group (CR, 55% with P = 0.267; OR, 74% with P = 0.086). Among patients who had progressive disease (PD) prior to CAR-T cell therapy, all six patients in the CD5-positive group exhibited PD after CAR-T cell therapy, whereas in the CD5-negative group, 7 of 26 (27%) patients achieved complete metabolic response. With a median follow-up of 12 months (interquartile range, 6.7-17 months), median progression-free survival (PFS) and overall survival (OS) were 5.0 and 16 months, respectively, in the CD5-positive group; and 20 months and not reached, respectively, in the CD5-negative group (log-rank test, P = 0.004 and P = 0.072). Multivariate analysis revealed that CD5 expression was unfavorably associated with PFS and OS. Together, these data suggest that CD5 expression has a negative impact on outcomes after CAR-T cell therapy.