Jurgens Eric M, Firestone Ross S, Chaudhari Jagrutiben, Hosszu Kinga, Devlin Sean M, Shah Urvi A, Landa Jonathan, McAvoy Devin P, Lesokhin Alexander M, Korde Neha, Hassoun Hani, Tan Carlyn R, Hultcrantz Malin, Shah Gunjan L, Landau Heather J, Chung David J, Scordo Michael, Eren Ozgur Can, Dogan Ahmet, Giralt Sergio A, Park Jae H, Rivière Isabelle, Brentjens Renier J, Smith Eric L, Wang Xiuyan, Usmani Saad Z, Mailankody Sham
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY.
J Clin Oncol. 2025 Feb 10;43(5):498-504. doi: 10.1200/JCO-24-01785. Epub 2024 Dec 4.
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 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.
MCARH109是一种用于复发/难治性多发性骨髓瘤患者的一流的靶向G蛋白偶联受体C类第5组成员D（GPRC5D）的嵌合抗原受体（CAR）T细胞疗法。这项I期临床试验纳入了17名患者，并确定MCARH109在最大耐受剂量为150×10的CAR T细胞时是安全的。在这项更新分析中，中位随访37个月时未报告新的严重不良事件。总体而言，17名患者中有12名（71%）有反应，包括10名先前接受过靶向B细胞成熟抗原治疗的患者中的7名（70%）。中位反应持续时间为8.6个月（95%CI，5.7至未达到[NR]），两名患者在最后一次随访时分别在32个月和41个月时维持严格的完全缓解。中位总生存期（OS）未达到，3年OS估计值为59%（95%CI，40至88）。复发时，10名患者中有6名（60%）通过免疫组化观察到可能的GPRC5D缺失。基于高维光谱细胞术的免疫分析将采集时的活化T细胞表型与对MCARH109的反应相关联。
