高危细胞遗传学的复发多发性骨髓瘤患者中伊沙妥昔单抗联合卡非佐米和地塞米松：IKEMA 亚组分析。
Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis.
机构信息
1st Department of Medicine-Department of Hematology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic.
University of Nantes, Nantes, France.
出版信息
Eur J Haematol. 2022 Nov;109(5):504-512. doi: 10.1111/ejh.13835. Epub 2022 Aug 18.
INTRODUCTION
The presence of high-risk chromosomal abnormalities [t(4;14), del(17p), and t(14;16)] has been linked with inferior outcomes in patients with multiple myeloma (MM). A prespecified interim analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d; Isa-Kd) significantly improved progression-free survival (PFS) versus Kd in patients with relapsed MM. This prespecified subgroup analysis of IKEMA examined efficacy and safety in patients with high-risk cytogenetics.
METHODS
High-risk cytogenetics was assessed by central laboratory and patients were classified as high risk if abnormalities were present in ≥1 of the following: del(17p): 50% cutoff; t(4;14), and/or t(14;16): 30% cutoff.
RESULTS
Of the randomized patients, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk chromosomal abnormality. A PFS benefit was seen in favor of Isa-Kd for patients with standard-risk (HR 0.440; 95% CI 0.266-0.728) and high-risk cytogenetics (HR 0.724; 95% CI 0.361-1.451). Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd (85.7%) versus Kd (63.3%) in patients with high-risk cytogenetics; however, the incidence of serious TEAEs (64.3% vs. 66.7%) was similar.
CONCLUSIONS
Isa-Kd is a new treatment option for the difficult-to-treat subgroup of patients with relapsed MM and high-risk cytogenetics.
简介
高风险染色体异常[ t(4;14)、del(17p)和 t(14;16)]与多发性骨髓瘤（MM）患者的不良预后相关。3 期 IKEMA 研究（NCT03275285）的一项预先指定的中期分析表明，伊沙妥昔单抗（Isa）+卡非佐米（K）和地塞米松（d；Isa-Kd）与 Kd 相比，显著改善了复发 MM 患者的无进展生存期（PFS）。IKEMA 的这项预先指定的亚组分析检查了高危细胞遗传学患者的疗效和安全性。
方法
高危细胞遗传学通过中心实验室评估，患者被归类为高危，如果存在以下一种或多种异常：del(17p)：50%截断值；t(4;14)和/或 t(14;16)：30%截断值。
结果
在随机分组的患者中，23.5%（Isa-Kd）和 25.2%（Kd）有≥1 种高危染色体异常。对于标准风险（HR 0.440；95%CI 0.266-0.728）和高危细胞遗传学患者（HR 0.724；95%CI 0.361-1.451），Isa-Kd 有利于 PFS。高危细胞遗传学患者中，Isa-Kd 治疗相关的 3 级及以上不良事件（TEAEs）发生率高于 Kd（85.7%比 63.3%）；然而，严重 TEAEs（64.3%比 66.7%）的发生率相似。
结论
对于复发 MM 和高危细胞遗传学的难治疗亚组患者，Isa-Kd 是一种新的治疗选择。
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