Phase I Trial of MCARH109, a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma: An Updated Analysis
Abstract
MCARH109 is a first-in-class G protein–coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory multiple myeloma. This phase I clinical trial included 17 patients and determined that MCARH109 is safe at a maximum tolerated dose of 150 × 10 6 CAR T cells. In this updated analysis, no new serious adverse events were reported at a median follow-up of 37 months. Overall, 12 (71%) of 17 patients responded, including seven (70%) of 10 patients previously treated with B-cell maturation antigen-targeted therapy. The median duration of response was 8.6 months (95% CI, 5.7 to not reached [NR]) with two patients sustaining a stringent complete response at the time of last follow-up, 32 months and 41 months, respectively. The median overall survival (OS) was NR and the 3-year OS estimate was 59% (95% CI, 40 to 88). Possible GPRC5D loss via immunohistochemistry was observed in 6 (60%) of 10 patients at relapse. High-dimensional spectral cytometry–based immune profiling associated an activated T-cell phenotype at apheresis with a response to MCARH109.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (27)
Eric M. Jurgens
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Ross S. Firestone
Memorial Sloan Kettering Cancer Center
Jagrutiben Chaudhari
Memorial Sloan Kettering Cancer Center, New York, New York, United States
Kinga Hosszu
Memorial Sloan Kettering Cancer Center, New York, New York, United States
Sean M. Devlin
Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
Urvi A. Shah
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Jonathan Landa
Memorial Sloan Kettering Cancer Center, New York, New York, United States
Devin P. McAvoy
Immune Discovery and Modeling Service, Memorial Sloan Kettering Cancer Center, New York, NY
Alexander M. Lesokhin
Memorial Sloan Kettering Cancer Center
Neha Korde
1Memorial Sloan Kettering Cancer Center, Myeloma Service, Department of Medicine, New York, United States
Hani Hassoun
1Memorial Sloan Kettering Cancer Center, Myeloma Service, Department of Medicine, New York, United States
Carlyn R. Tan
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Malin Hultcrantz
1Memorial Sloan Kettering Cancer Center, Myeloma Service, Department of Medicine, New York, United States
Gunjan L. Shah
Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
Heather J. Landau
Memorial Sloan-Kettering Cancer Center, New York, New York, United States
David J. Chung
Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Michael Scordo
Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
Ozgur Can Eren
Hematopathology Service, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York
Ahmet Dogan
Hematopathology Service, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York
Sergio A. Giralt
Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
Jae H. Park
Isabelle Rivière
Center for Cell Engineering, Sloan Kettering Institute, New York, NY
Renier J. Brentjens
Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States
Eric L. Smith
Xiuyan Wang
Saad Z. Usmani
Memorial Sloan Kettering Cancer Center, New York
Sham Mailankody
Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York