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
Eric M. Jurgens, Ross Firestone, Jagrutiben Chaudhari, Kinga Hosszu, Sean M. Devlin, Urvi A. Shah, Jonathan Landa, Devin McAvoy, Alexander M. Lesokhin, Neha Korde, Hani Hassoun, Carlyn Tan, Malin Hultcrantz, Gunjan L. Shah, Heather Landau, David J. Chung, Michael Scordo, Özgür Can Eren, Ahmet Doǧan, Sergio Giralt, Jae H. Park, Isabelle Rivière, Renier J. Brentjens, Eric L. Smith, Xiuyan Wang, Saad Z. Usmani, Sham Mailankody
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.