在骨髓瘤中进行 TIGIT-LAG3 阻断后的临床反应和通路特异性相关性：MyCheckpoint 随机临床试验。
Clinical response and pathway-specific correlates following TIGIT-LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial.
机构信息
Tisch Cancer Institute, Icahn School of Medicine, New York, NY, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
出版信息
Nat Cancer. 2024 Oct;5(10):1459-1464. doi: 10.1038/s43018-024-00818-w. Epub 2024 Aug 26.
Abstract
Persons with myeloma were randomized to receive an anti-TIGIT (T cell immunoreceptor) or anti-LAG3 (lymphocyte activation gene) antibody followed by combination with pomalidomide and dexamethasone ( NCT04150965 ). Primary and secondary endpoints were safety and efficacy, respectively. Therapy was well tolerated without dose-limiting toxicity. Durable clinical responses were observed in both the anti-TIGIT(three of six participants) and the anti-LAG3 (two of six participants) arms. Anti-LAG3 responders had higher naive cluster of differentiation 4 (CD4)-positive T cells and lower programmed cell death protein 1-positive effector T cells. Anti-TIGIT responders had higher CD226 expression, natural killer cell activation and lower CD112 expression. These data demonstrate the clinical activity of TIGIT-LAG3 blockade and identify pathway-specific response correlates in myeloma.
摘要
多发性骨髓瘤患者被随机分配接受抗 TIGIT（T 细胞免疫受体）或抗 LAG3（淋巴细胞激活基因）抗体治疗，随后联合泊马度胺和地塞米松（NCT04150965）。主要和次要终点分别为安全性和疗效。治疗耐受性良好，无剂量限制毒性。在抗 TIGIT（六名参与者中的三名）和抗 LAG3（六名参与者中的两名）臂均观察到持久的临床反应。抗 LAG3 应答者具有更高的幼稚 CD4 阳性 T 细胞和更低的程序性细胞死亡蛋白 1 阳性效应 T 细胞。抗 TIGIT 应答者具有更高的 CD226 表达、自然杀伤细胞激活和更低的 CD112 表达。这些数据表明 TIGIT-LAG3 阻断具有临床活性，并确定多发性骨髓瘤中特定途径的反应相关性。
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