Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR.
Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR.
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DOI：
10.1200/jco.20.01814
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发表时间：
2021-04-01
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通讯作者：
Bahlis NJ
中科院分区：
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作者：
Avet-Loiseau H;San-Miguel J;Casneuf T;Iida S;Lonial S;Usmani SZ;Spencer A;Moreau P;Plesner T;Weisel K;Ukropec J;Chiu C;Trivedi S;Amin H;Krevvata M;Ramaswami P;Qin X;Qi M;Sun S;Qi M;Kobos R;Bahlis NJ
在复发性和/或难治性多发性骨髓瘤中，达雷妥尤单抗使POLLUX（达雷妥尤单抗/来那度胺/地塞米松[D-Rd]）和CASTOR（达雷妥尤单抗/硼替佐米/地塞米松[D-Vd]）的进展或死亡风险降低> 60%。微小残留病（MRD）是一种敏感的疾病控制措施。在这些研究中评价了持续MRD阴性和结局。在两项研究中，在疑似完全缓解（CR）、确认CR后3个月和6个月（POLLUX）、首次给药后6个月和12个月（CASTOR）以及CR后每12个月，通过下一代测序（10−5）评估MRD。在意向治疗（ITT）和≥ CR人群中评价了持续MRD阴性（≥ 6个月或≥ 12个月）。POLLUX和CASTOR的中位随访时间分别为54.8个月和50.2个月。在ITT人群中，D-Rd与来那度胺和地塞米松（Rd）的MRD阴性率分别为32.5%和6.7%，D-Vd与硼替佐米和地塞米松（Vd;均P < .0001）的MRD阴性率分别为15.1%和1.6%。POLLUX（D-Rd，57.4%; Rd，29.2%; P = .0001）和CASTOR（D-Vd，52.8%; Vd，17.4%; P = .0035）中≥ CR患者的MRD阴性率较高。在ITT人群中，D-Rd与Rd相比，更多患者达到持续MRD阴性≥ 6个月（20.3%对2.1%; P < .0001）和D-Vd对Vd（10.4%对1.2%; P < .0001），以及≥ 12个月时D-Rd与Rd（16.1%对1.4%; P < .0001）和D-Vd与Vd（6.8%对0%）。在≥ CR患者中观察到了类似的MRD持续阴性结果。含达雷妥尤单抗组中更多患者达到MRD阴性和持续MRD阴性，这与无进展生存期延长相关。与标准治疗相比，基于Daratumumab的联合治疗诱导的持续MRD阴性率更高，这与持久缓解和延长临床结局相关。
In relapsed and/or refractory multiple myeloma, daratumumab reduced the risk of progression or death by > 60% in POLLUX (daratumumab/lenalidomide/dexamethasone [D-Rd]) and CASTOR (daratumumab/bortezomib/dexamethasone [D-Vd]). Minimal residual disease (MRD) is a sensitive measure of disease control. Sustained MRD negativity and outcomes were evaluated in these studies. MRD was assessed via next-generation sequencing (10−5) at suspected complete response (CR), 3 and 6 months following confirmed CR (POLLUX), 6 and 12 months following the first dose (CASTOR), and every 12 months post-CR in both studies. Sustained MRD negativity (≥ 6 or ≥ 12 months) was evaluated in the intention-to-treat (ITT) and ≥ CR populations. The median follow-up was 54.8 months in POLLUX and 50.2 months in CASTOR. In the ITT population, MRD-negativity rates were 32.5% versus 6.7% for D-Rd versus lenalidomide and dexamethasone (Rd) and 15.1% versus 1.6% for D-Vd versus bortezomib and dexamethasone (Vd; both P < .0001). Higher MRD negativity rates were achieved in ≥ CR patients in POLLUX (D-Rd, 57.4%; Rd, 29.2%; P = .0001) and CASTOR (D-Vd, 52.8%; Vd, 17.4%; P = .0035). More patients in the ITT population achieved sustained MRD negativity ≥ 6 months with D-Rd versus Rd (20.3% v 2.1%; P < .0001) and D-Vd versus Vd (10.4% v 1.2%; P < .0001), and ≥ 12 months with D-Rd versus Rd (16.1% v 1.4%; P < .0001) and D-Vd versus Vd (6.8% v 0%). Similar results for sustained MRD negativity were observed among ≥ CR patients. More patients in the daratumumab-containing arms achieved MRD negativity and sustained MRD negativity, which were associated with prolonged progression-free survival. Daratumumab-based combinations induce higher rates of sustained MRD negativity versus standard of care, which are associated with durable remissions and prolonged clinical outcomes.