近日，中国医学科学院北京协和医学院张磊团队研究了抗CD38单克隆抗体CM313治疗原发性免疫性血小板减少症的多中心、随机、安慰剂对照、2期试验。该研究于2025年10月21日发表在《英国医学杂志》上。

为了评估CM313（一种抗CD38单克隆抗体）治疗持续性或慢性原发性免疫性血小板减少症的有效性和安全性，2024年1月16日至6月11日，研究组在中国五家医院进行了一项多中心、随机、安慰剂对照的2期临床试验。共招募了45例年龄≥18岁的持续性或慢性免疫性血小板减少患者，均对糖皮质激素治疗无效或治疗后复发，但先前对标准一线治疗有反应。这些患者随机接受静脉注射CM313 （16 mg/kg）或安慰剂，每周8周。主要终点是第8周的总缓解率（至少连续两次血小板计数≥30×10⁹/L，较基线至少翻倍，无出血）。次要终点是前两个连续血小板计数≥50×10⁹/L的时间。

在筛选的56例患者中，45例随机接受CM313 （n=30）或安慰剂（n=15）。在第8周，CM313组的总有效率（83%;25/30）高于安慰剂组（20%;3/15）：差异63.3%（95%可信区间33.7%至81.3%;P<0.001）。CM313组达到血小板计数≥50×10⁹/L的中位时间为1周，而安慰剂组没有达到（P<0.001）。CM313组血小板计数≥50×10⁹/L的中位累积反应持续时间为18周，而安慰剂组为3周（P=0.004）。在CM313组中，87%（26/30）的患者出现了治疗紧急不良事件，在安慰剂组中，80%（12/15）的患者出现了治疗紧急不良事件，其中输液相关反应和瘀点是最常见的。

研究结果表明，CM313在成人持续性或慢性原发性免疫性血小板减少症患者中表现出良好的安全性和令人鼓舞的疗效，其特点是血小板计数快速增加，血小板反应持续，不良事件可控。

附：英文原文

Title: Anti-CD38 monoclonal antibody CM313 for primary immune thrombocytopenia: multicentre, randomised, placebo controlled, phase 2 trial

Author: Yunfei Chen, Yanmei Xu, Jiawen Dai, Ting Sun, Huiyuan Li, Zhengjie Hua, Zeping Zhou, Hu Zhou, Zhenyu Yan, Xingli Zhao, Feng Xue, Wei Liu, Xiaofan Liu, Rongfeng Fu, Wentian Wang, Ying Chi, Huan Dong, Mankai Ju, Xinyue Dai, Wenjing Gu, Xiaolei Pei, Renchi Yang, Lei Zhang

Issue&Volume: 2025/10/21

Abstract:

Objective To assess the efficacy and safety of CM313, an anti-CD38 monoclonal antibody, in adults with persistent or chronic primary immune thrombocytopenia.

Design Multicentre, randomised, placebo controlled, phase 2 trial.

Setting Five hospitals in China, 16 January to 11 June 2024.

Participants 45 patients aged ≥18 years with persistent or chronic immune thrombocytopenia who failed to respond to, or relapsed after, glucocorticoid treatment but had previously responded to standard first line treatment.

Interventions Patients were randomised to receive intravenous CM313 (16 mg/kg) or placebo weekly for eight weeks.

Main outcome measures The primary outcome was overall response rate (at least two consecutive platelet counts ≥30×109/L, a minimum doubling from baseline, and no bleeding) at week 8. A secondary outcome was time to the first two consecutive platelet counts ≥50×109/L.

Results Of 56 patients screened, 45 were randomised to receive CM313 (n=30) or placebo (n=15). At week 8, the overall response rate was higher in the CM313 group (83%; 25/30) compared with placebo group (20%; 3/15): difference 63.3% (95% confidence interval 33.7% to 81.3%; P<0.001). The median time to a platelet count of ≥50×109/L was one week in the CM313 group but was not reached in the placebo group (P<0.001). The median cumulative response duration for platelet counts ≥50×109/L was 18 weeks in the CM313 group versus three weeks in the placebo group (P=0.004). Treatment emergent adverse events occurred in 87% (26/30) of patients in the CM313 group and 80% (12/15) in the placebo group, with infusion related reactions and petechiae being the most common.

Conclusion CM313 showed a favourable safety profile and encouraging efficacy in adults with persistent or chronic primary immune thrombocytopenia, characterised by rapid increase in platelet count, sustained platelet responses, and manageable adverse events.

DOI: 10.1136/bmj-2025-084314

Source: https://www.bmj.com/content/391/bmj-2025-084314