CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Iberdomide increases innate and adaptive immune cell subsets in the bone marrow of patients with relapsed/refractory multiple myeloma.
Iberdomide increases innate and adaptive immune cell subsets in the bone marrow of patients with relapsed/refractory multiple myeloma.
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Iberdomide 是一种强效的 cereblon E3 连接酶调节剂（CELMoD 药物），作为单药或与其他疗法联合治疗复发/难治性多发性骨髓瘤（RRMM）患者时，具有令人鼓舞的疗效和安全性。
我们使用为骨髓肿瘤微环境（TME）大规模免疫表型分析设计的定制质谱流式细胞术 panel，在 93 例接受 iberdomide 治疗的多发性骨髓瘤（MM）患者队列中证明效应 T 细胞和自然杀伤（NK）细胞显著增加，并将这些发现与疾病特征、既往治疗和外周血免疫表型相关联。
值得注意的是，这些变化具有剂量依赖性，与客观缓解相关，并且独立于既往对 MM 治疗的难治性。这表明 iberdomide 在 TME 中广泛诱导固有免疫和适应性免疫激活，从而促进其抗肿瘤疗效。
我们的方法建立了一种策略，用于研究 MM 患者以及更广泛地癌症患者中治疗诱导的 TME 变化，并为 iberdomide 与免疫增强疗法联合治疗 MM 建立了合理的联合策略。
Iberdomide is a potent cereblon E3 ligase modulator (CELMoD agent) with promising efficacy and safety as a monotherapy or in combination with other therapies in patients with relapsed/refractory multiple myeloma (RRMM).
Using a custom mass cytometry panel designed for large-scale immunophenotyping of the bone marrow tumor microenvironment (TME), we demonstrate significant increases of effector T and natural killer (NK) cells in a cohort of 93 patients with multiple myeloma (MM) treated with iberdomide, correlating findings to disease characteristics, prior therapy, and a peripheral blood immune phenotype.
Notably, changes are dose dependent, associated with objective response, and independent of prior refractoriness to MM therapies. This suggests that iberdomide broadly induces innate and adaptive immune activation in the TME, contributing to its antitumor efficacy.
Our approach establishes a strategy to study treatment-induced changes in the TME of patients with MM and, more broadly, patients with cancer and establishes rational combination strategies for iberdomide with immune-enhancing therapies to treat MM.
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