A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia

作者：Yunfei Chen, Yanmei Xu, Huiyuan Li, Ting Sun, Xuan Cao, Yuhua Wang, Feng Xue, Wei Liu, Xiaofan Liu, H. Dong, Rongfeng Fu, Xinyue Dai, Wentian Wang, Yueshen Ma, Zhen Song, Ying Chi, Mankai Ju, Wenjing Gu, Xiaolei Pei, Renchi Yang, Lei Zhang · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2400409 · 被引用次数：48 · 研究领域：Platelet Disorders and Treatments、Autoimmune Bullous Skin Diseases、Multiple Myeloma Research and Treatments

Background Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells. Methods We conducted a phase 1–2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP. CM313 was administered intravenously at a dose of 16 mg per kilogram of body weight every week for 8 weeks, followed by a 16-week follow-up period. The primary outcomes were adverse events and documentation of two or more consecutive platelet counts of at least 50×10 9 per liter within 8 weeks after the first dose of CM313. The status of peripheral-blood immune cells in patients and changes in the mononuclear phagocytic system in passive mouse models of ITP receiving anti-CD38 therapy were monitored. Results Of the 22 patients included in the study, 21 (95%) had two consecutive platelet counts of at least 50×10 9 per liter during the treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17 to 24). The median time to the first platelet count of at least 50×10 9 per liter was 1 week (range, 1 to 3). The most common adverse events that occurred during the study were infusion-related reaction (in 32% of the patients) and upper respiratory tract infection (in 32%). After CD38-targeted therapy, the percentage of CD56 dim CD16+ natural killer cells, the exp...