Abstract / Summary
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 . Extended follow-up of four patients with multiple myeloma treated with in vivo BCMA CAR-T cells showed limited duration of response in three patients, while one patient had sustained response to 15 months.