LAUSR

The cost and toxicities of chimeric antigen receptor (CAR)-T cells require efforts to identify the patients most likely to respond. We determined whether the quality of T lymphocytes at the time of apheresis influenced the clinical response to commercial tisagenlecleucel (tisa-cel) in 30 large B-cell lymphoma patients. The T-cell phenotype and proliferative capacity were determined by flow cytometry. Clinical efficacy outcome (partial or complete response at 1 and 3 months, progression-free survival (PFS) and overall survival (OS)) was evaluated based on the Lugano criteria. The proportion of naïve/stem cell memory (TN/SCM) correlated with the proliferative potential of CD4 and CD8 T cells, and with the relative expansion of CD4 and CD8 subsets during CAR-T cell manufacture. Early clinical response, PFS and OS were positively associated with higher proportions of CD8 TN/SCM and higher CD8 T-cell proliferative potential, while CD4 T cells had opposite effects. In multivariate analysis, CD8 TN/SCM proportion and International Prognostic Index (IPI) at the time of apheresis were independent risk factors for early progression. Our data show that an easy characterization by flow cytometry of the T-cell phenotype at the time of decision to use commercial CAR-T cells can help to better select patients who will respond.