Extended follow-up of in vivo BCMA CAR-T therapy in relapsed/refractory multiple myeloma.

Data on long-term outcomes of in vivo chimeric antigen receptor T cell (CAR‑T) therapy remain scarce. We previously reported preliminary safety and efficacy data of in vivo B-cell maturation antigen (BCMA) CAR‑T (ESO-T01), in four patients with relapsed/refractory multiple myeloma, without leukapheresis and lymphodepletion, with up to 3 months of follow-up. The primary endpoints included safety and tolerability, while the secondary endpoints comprised efficacy, pharmacokinetics and pharmacodynamics. All patients developed dual-phase cytokine release syndrome (grades 1-3) and hematotoxicities (grade ≥3). One patient developed grade 1 immune effector cell-associated neurotoxicity syndrome. The objective response rate reached 100% (two stringent complete response and two partial response). Here we update the data on long‑term safety and response durability with a maximal follow‑up of 15 months. No immunogenicity‑ or integration‑related toxicities occurred, and no important adverse events related to ESO-T01 emerged beyond the initial report. Of the four patients, one maintained stringent complete response for 15 months. The median progression-free survival was 4.0 (range 3.0-15.0) months. After progression, diverse salvage therapies extended overall survival to 5.5-10.9 months after infusion. Three patients experienced relapse or progression, all with extramedullary involvement, and eventually died during follow-up. One patient achieved durable response with robust expansion from ex vivo CAR-T. Collectively, these updated results provide additional insights on the safety and efficacy of in vivo CAR-T therapies. The limited persistence observed necessitates the further optimization of the in vivo CAR-T platform. ClinicalTrials.gov identifier: NCT06691685 .