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在Ib期试验中,综合单细胞免疫分析定义了患者多发性骨髓瘤微环境,该微环境是在瘤病毒治疗后的

Steffan T Nawrocki¹, Julian Olea², Claudia Villa Celi²

¹Division of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Arizona.

Clinical cancer research : an official journal of the American Association for Cancer Research

|October 9, 2023

概括

佩拉雷欧普 (PELA) 与博尔特佐米布和德克萨米结合显示出抗髓瘤活性,并调节了多发性髓瘤患者的瘤免疫微环境.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
病毒学病毒学

背景情况:

临床前研究表明,瘤性转录病毒配方佩拉雷欧雷普 (PELA) 具有显著的免疫调节和抗髓瘤特性.
多发性骨髓瘤是一种血液性恶性瘤,其特征是血细胞的不受控制的增殖.

研究的目的:

评估PELA与甲 (Dex) 和博特佐米布 (BZ) 结合的安全性和有效性,用于复发/耐药多发性髓瘤患者.
用PELA/Dex/BZ.进行治疗后,描述瘤免疫微环境 (TiME) 的变化.

主要方法:

一项Ib期临床试验招募了14名复发/耐药多发性髓瘤患者.
患者接受了PELA的升级剂量与Dex和BZ的标准剂量相结合,治疗周期每28天重复一次.
骨髓和外周血液样本在治疗前和治疗后收集,以进行全面的免疫类型和分子分析.

主要成果:

PELA/BZ/Dex疗法耐受性良好,有过渡性毒性,没有观察到剂量限制性毒性.
在可评估应答的11名患者中,6名 (55%) 显示了偏蛋白水平的降低.
治疗导致T细胞和自然杀手细胞活化增加,炎症性细胞因子释放增加,骨髓中PD-L1表达增强.

结论:

PELA/Dex/BZ是一种可容忍的组合疗法,在一组患者中表现出抗髓瘤活性.
治疗诱导了显著的免疫重编程和TiME的变化.
这些发现支持进一步调查PELA作为多发性骨髓瘤的免疫调节剂.

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