GPRC5D-Targeted CAR T Cells for Myeloma
Sham Mailankody, Sean M. Devlin, Jonathan Landa, Karthik Nath, Claudia Diamonte, Elizabeth J. Carstens, Douglas Russo, Romany Auclair, Lisa Fitzgerald, Briana Cadzin, Xiuyan Wang, Devanjan Sikder, Brigitte Sénéchal, Vladimir P. Bermudez, Terence J. Purdon, Kinga Hosszu, Devin McAvoy, Tasmin Farzana, Elena Mead, Jessica Wilcox, Bianca Santomasso, Gunjan L. Shah, Urvi A. Shah, Neha Korde, Alexander M. Lesokhin, Carlyn Tan, Malin Hultcrantz, Hani Hassoun, Mikhail Roshal, Filiz Şen, Ahmet Doǧan, Ola Landgren, Sergio Giralt, Jae H. Park, Saad Z. Usmani, Isabelle Rivière, Renier J. Brentjens, Eric L. Smith
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.).