文章：

达雷妥尤单抗、来那度胺和地塞米松治疗复发/难治性骨髓瘤：POLLUX研究的细胞遗传学亚组分析

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

原文发布日期：2020-11-03

DOI: 10.1038/s41408-020-00375-2

类型: Article

开放获取: 是

英文摘要：

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk.
 

摘要翻译： 

高危细胞遗传学异常会导致多发性骨髓瘤患者预后不良。在POLLUX研究中，达雷妥尤单抗/来那度胺/地塞米松（D-Rd）相较于来那度胺/地塞米松（Rd）在复发/难治性多发性骨髓瘤（RRMM）患者中展现出显著临床获益。本文报告基于细胞遗传学风险的POLLUX最新亚组分析。通过荧光原位杂交/核型分析确定细胞遗传学风险；高危患者存在t(4;14)、t(14;16)或del17p异常。采用clonoSEQ®检测V2.0评估微小残留病（MRD；10-5阈值）。共569例患者入组（D-Rd组286例，Rd组283例）；每组各有35例（12%）患者属于高危群体。中位随访44.3个月后，在标准细胞遗传学风险（中位PFS：未达到 vs 18.6个月；风险比[HR] 0.43；P<0.0001）和高危细胞遗传学风险（中位PFS：26.8 vs 8.3个月；HR 0.34；P=0.0035）患者中，D-Rd均较Rd显著延长无进展生存期。无论细胞遗传学风险如何，D-Rd组均获得更深层次的缓解，包括更高的MRD阴性率和持续MRD阴性率。在两组细胞遗传学风险亚组中，D-Rd后续治疗线的无进展生存期均优于Rd。不同细胞遗传学风险亚组的D-Rd安全性与总体人群一致。这些研究结果证实，无论细胞遗传学风险如何，达雷妥尤单抗联合标准治疗方案在RRMM中的疗效均优于单纯标准治疗。

原文链接：

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX