Synapse - GPRC5D-targeted CAR T cells for myeloma

GPRC5D-targeted CAR T cells for myeloma Journal Article

Authors:	Mailankody, S.; Devlin, S. M.; Landa, J.; Nath, K.; Diamonte, C.; Carstens, E. J.; Russo, D.; Auclair, R.; Fitzgerald, L.; Cadzin, B.; Wang, X.; Sikder, D.; Senechal, B.; Bermudez, V. P.; Purdon, T. J.; Hosszu, K.; McAvoy, D. P.; Farzana, T.; Mead, E.; Wilcox, J. A.; Santomasso, B. D.; Shah, G. L.; Shah, U. A.; Korde, N.; Lesokhin, A.; Tan, C. R.; Hultcrantz, M.; Hassoun, H.; Roshal, M.; Sen, F.; Dogan, A.; Landgren, O.; Giralt, S. A.; Park, J. H.; Usmani, S. Z.; Rivière, I.; Brentjens, R. J.; Smith, E. L.
Article Title:	GPRC5D-targeted CAR T cells for myeloma
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: A total of 17 patients were enrolled and received MCARH109 therapy. The maximum tolerated dose was identified at 150×106 CAR T cells. At the 450×106 CAR T-cell dose, 1 patient had grade 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), and 2 patients had a grade 3 cerebellar disorder of unclear cause. No cerebellar disorder, ICANS of any grade, or cytokine release syndrome of grade 3 or higher occurred in the 12 patients who received doses of 25×106 to 150×106 cells. A response was reported in 71% of the patients in the entire cohort and in 58% of those who received doses of 25×106 to 150×106 cells. The patients who had a response included those who had received previous BCMA therapies; responses were observed in 7 of 10 such patients in the entire cohort and in 3 of 6 such patients who received 25×106 to 150×106 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.). Copyright © 2022 Massachusetts Medical Society.
Keywords:	t lymphocyte; t-lymphocytes; multiple myeloma; neoplasm recurrence, local; tumor recurrence; receptors, g-protein-coupled; g protein coupled receptor; adoptive immunotherapy; immunotherapy, adoptive; etiology; adverse event; cytokine release syndrome; procedures; humans; human; b cell maturation antigen; b-cell maturation antigen; receptors, chimeric antigen; gprc5d protein, human
Journal Title:	New England Journal of Medicine
Volume:	387
Issue:	13
ISSN:	0028-4793
Publisher:	Massachusetts Medical Society
Date Published:	2022-09-29
Start Page:	1196
End Page:	1206
Language:	English
DOI:	10.1056/NEJMoa2209900
PUBMED:	36170501
PROVIDER:	scopus
PMCID:	PMC10309537
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85138911676&doi=10.1056%2fNEJMoa2209900&partnerID=40&md5=7b4f39e5ffca4b62ee7289127941c587
Notes:	Article -- Export Date: 1 November 2022 -- Source: Scopus