Abstract Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a non-enriched product, thereby improving duration of response (DOR). We conducted a phase 1 study with bb21217 (NCT03274219), an anti-B-cell maturation antigen CAR T-cell therapy manufactured in the presence of bb007 (phosphoinositide 3-kinase inhibitor) to enrich for T cells with a memory-like phenotype, in patients with relapsed/refractory multiple myeloma (N=72). No new safety concerns were raised with bb21217 therapy (three cases each of grade ≥3 CRS and grade ≥3 neurotoxicity were observed). The objective response rate was 69.4% and median DOR was 23.8 (95% confidence interval, 16.8–34.8) months. Analysis of drug product established an association between early memory phenotype and robust expansion and depth of response. Examination of baseline characteristics indicated that tumor burden and prior therapies influenced DOR. The generation of CAR T cells early in a disease course when tumor burden is lower and source material exhibits a more naïve phenotype may maximize the clinical benefit potential of the drug product.
Alsina et al. (Wed,) studied this question.
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