• Yunfei Chen, Yanmei Xu, Huiyuan Li, Ting Sun, Xuan Cao, Yuhua Wang, Feng Xue, Wei Liu, Xiaofan Liu, Huan Dong, Rongfeng Fu, Xinyue Dai, Wentian Wang, Yueshen Ma, Zhen Song, Ying Chi, Mankai Ju, Wenjing Gu, Xiaolei Pei, Renchi Yang, and Lei Zhang.
• From the National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, Chinese Academy of Medical Sciences Key Laboratory of Gene Therapy for Blood Diseases, and the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and the Tianjin Institutes of Health Science, Tianjin (Y.C., Y.X., H.L., T.S., X.C., Y.W., F.X., W.L., X.L., H.D., R.F., X.D., W.W., Y.M., Z.S., Y.C., M.J., W.G., X.P., R.Y., L.Z.), and the School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (L.Z.) - all in China.
• N. Engl. J. Med. 2024 Jun 20; 390 (23): 217821902178-2190.

BackgroundImmune 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.MethodsWe 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 50×109 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.ResultsOf the 22 patients included in the study, 21 (95%) had two consecutive platelet counts of at least 50×109 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 50×109 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 CD56dimCD16+ natural killer cells, the expression of CD32b on monocytes in peripheral blood, and the number of macrophages in the spleen of the passive mouse models of ITP all decreased.ConclusionsIn this study, anti-CD38 targeted therapy rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets, maintained long-term efficacy by clearing plasma cells, and was associated with mainly low-grade toxic effects. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and others; ClinicalTrials.gov number, NCT05694767).Copyright © 2024 Massachusetts Medical Society.

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