Posted: Friday, November 18, 2022
Based on “promising” preclinical results, co-senior authors Renier J. Brentjens, MD, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, and Eric L. Smith, MD, PhD, of Dana-Farber Cancer Center, Boston, along with colleagues conducted a phase I dose-escalation study of the G protein–coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy—MCARH109—in patients with heavily pretreated multiple myeloma. The results, which were published in The New England Journal of Medicine, confirm GPRC5D as an active immunotherapeutic target.
“In this first small study, [MCARH109] demonstrated a strong response rate in patients, even [in] those who were previously treated with [B-cell maturation antigen (BCMA)-directed therapies],” Dr. Brentjens commented in an institutional press release. “It’s a proof-of-principle study, but these results provide a rationale for not just infusing a single population of CAR T cells, but using several populations that may be targeted to different proteins on the surface of the tumor cell.”
Using a 3 + 3 dose-escalation scheme, 17 patients from the Memorial Sloan Kettering Cancer Center, New York, were administered MCARH109 at four dose levels: 25, 50, 150, and 450 × 106 total CAR T cells. The maximum tolerated dose was established as 150 × 106 cells. One patient who was treated with 450 × 106 cells experienced grade 4 cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome; grade 3 cerebellar disorder of an unclear cause was reported in two patients. No adverse events of grade 3 or higher were observed in the 12 patients who received doses up to the maximum tolerated dose.
A response was reported in 71% of the entire cohort and in 58% of those who received doses up to the maximum tolerated dose. The population that achieved a response included those who had received previous BCMA-directed therapies (entire cohort: n = 7/10; cohort dosed up to the maximum tolerated dose: n = 3/6).
Disclosure: For full disclosures of the study authors, visit nejm.org.