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 Senechal, Vladimir P Bermudez, Terence J Purdon, Kinga Hosszu, Devin P McAvoy, Tasmin Farzana, Elena Mead, Jessica A Wilcox, Bianca D Santomasso, Gunjan L Shah, Urvi A Shah, Neha Korde, Alexander Lesokhin, Carlyn R Tan, Malin Hultcrantz, Hani Hassoun, Mikhail Roshal, Filiz Sen, Ahmet Dogan, Ola Landgren, Sergio A Giralt, Jae H Park, Saad Z Usmani, Isabelle Rivière, Renier J Brentjens, Eric L Smith
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...
September 29, 2022: New England Journal of Medicine