Winship Cancer Institute, Emory University, Atlanta, GA, USA.
The National and Kapodistrian University of Athens, Athens, Greece.
Blood Cancer J. 2020 Nov 3;10(11):111. doi: 10.1038/s41408-020-00375-2.
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) 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.
高细胞遗传学风险异常导致多发性骨髓瘤患者预后不良。在 POLLUX 研究中，与来那度胺/地塞米松（Rd）相比，达雷妥尤单抗/来那度胺/地塞米松（D-Rd）在复发/难治性多发性骨髓瘤（RRMM）患者中显示出显著的临床获益。我们报告了基于细胞遗传学风险的 POLLUX 亚组分析更新结果。细胞遗传学风险使用荧光原位杂交/核型分析确定；高细胞遗传学风险患者具有 t(4;14)、t(14;16)或 del17p 异常。微小残留病（MRD；10）通过 clonoSEQ 检测 V2.0 进行评估。569 名患者被随机分组（D-Rd 组，n=286；Rd 组，n=283）；每组有 35 名（12%）患者具有高细胞遗传学风险。中位随访 44.3 个月后，D-Rd 延长了标准细胞遗传学风险（中位：不可估计 vs 18.6 个月；风险比[HR]，0.43；P<0.0001）和高细胞遗传学风险（中位：26.8 vs 8.3 个月；HR，0.34；P=0.0035）患者的无进展生存期（PFS）。D-Rd 治疗的反应很深，包括更高的 MRD 阴性率和持续的 MRD 阴性率，与细胞遗传学风险无关。与 Rd 相比，在两个细胞遗传学风险亚组中，D-Rd 治疗后下一线治疗的 PFS 得到改善。按细胞遗传学风险分层，D-Rd 的安全性与总体人群一致。这些结果表明，达雷妥尤单抗联合标准治疗与标准治疗相比，在 RRMM 中无论细胞遗传学风险如何，均能提高疗效。
