Tisch Cancer Institute, Icahn School of Medicine, New York, NY, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Cancer. 2024 Oct;5(10):1459-1464. doi: 10.1038/s43018-024-00818-w. Epub 2024 Aug 26.
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.
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。