GPRC5D-Targeted CAR T Cells for Myeloma

Sham Mailankody(United States Fish and Wildlife Service), Sean M. Devlin(United States Fish and Wildlife Service), Jonathan Landa(United States Fish and Wildlife Service), Karthik Nath(United States Fish and Wildlife Service), Claudia Diamonte(United States Fish and Wildlife Service), Elizabeth J. Carstens(United States Fish and Wildlife Service), Douglas Russo(United States Fish and Wildlife Service), Romany Auclair(United States Fish and Wildlife Service), Lisa Fitzgerald(United States Fish and Wildlife Service), Briana Cadzin(United States Fish and Wildlife Service), Xiuyan Wang(United States Fish and Wildlife Service), Devanjan Sikder(United States Fish and Wildlife Service), Brigitte Sénéchal(United States Fish and Wildlife Service), Vladimir P. Bermudez(United States Fish and Wildlife Service), Terence J. Purdon(United States Fish and Wildlife Service), Kinga Hosszu(United States Fish and Wildlife Service), Devin McAvoy(United States Fish and Wildlife Service), Tasmin Farzana(United States Fish and Wildlife Service), Elena Mead(United States Fish and Wildlife Service), Jessica Wilcox(United States Fish and Wildlife Service), Bianca Santomasso(United States Fish and Wildlife Service), Gunjan L. Shah(United States Fish and Wildlife Service), Urvi A. Shah(United States Fish and Wildlife Service), Neha Korde(United States Fish and Wildlife Service), Alexander M. Lesokhin(United States Fish and Wildlife Service), Carlyn Tan(United States Fish and Wildlife Service), Malin Hultcrantz(United States Fish and Wildlife Service), Hani Hassoun(United States Fish and Wildlife Service), Mikhail Roshal(United States Fish and Wildlife Service), Filiz Şen(United States Fish and Wildlife Service), Ahmet Doǧan(United States Fish and Wildlife Service), Ola Landgren(United States Fish and Wildlife Service), Sergio Giralt(United States Fish and Wildlife Service), Jae H. Park(United States Fish and Wildlife Service), Saad Z. Usmani(United States Fish and Wildlife Service), Isabelle Rivière(United States Fish and Wildlife Service), Renier J. Brentjens(United States Fish and Wildlife Service), Eric L. Smith(United States Fish and Wildlife Service)
New England Journal of Medicine
September 28, 2022
10.1056/nejmoa2209900
Cited by 381Open Access
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Abstract

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have generated responses in patients with advanced myeloma, but relapses are common. G protein-coupled receptor, class C, group 5, member D (GPRC5D) has been identified as an immunotherapeutic target in multiple myeloma. Preclinical studies have shown the efficacy of GPRC5D-targeted CAR T cells, including activity in a BCMA antigen escape model. METHODS: In this phase 1 dose-escalation study, we administered a GPRC5D-targeted CAR T-cell therapy (MCARH109) at four dose levels to patients with heavily pretreated multiple myeloma, including patients with relapse after BCMA CAR T-cell therapy. RESULTS: cells. CONCLUSIONS: The results of this study of a GPRC5D-targeted CAR T-cell therapy (MCARH109) confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma. (Funded by Juno Therapeutics/Bristol Myers Squibb; ClinicalTrials.gov number, NCT04555551.).

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