PDF(Pubmed)
Abstract：
Ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) showed clinical efficacy over placebo-Rd in patients with relapsed/refractory multiple myeloma (MM) in the TOURMALINE-MM1 trial. Over a median follow-up of ∼85 months, as patients showed disease progression, they received subsequent novel therapies that confounded the overall survival (OS) benefit. Here, we conducted a post hoc analysis in 148 patients from seven countries defined as emerging markets, with limited access to novel therapies for MM during the trial period, to describe the impact of these therapies on OS. Patients were randomised to ixazomib-Rd (n = 71) or placebo-Rd (n = 77). The median progression-free survival (PFS) was 18.7 versus 10.2 months, with ixazomib-Rd versus placebo-Rd (hazard ratio [HR], 0.504; p = 0.008) demonstrating a statistically significant improvement as observed in the primary trial. The median OS improved by 32.6 months with ixazomib-Rd over placebo-Rd (63.5 vs. 30.9 months; HR, 0.794; p = 0.261); however, the statistically significant benefit seen in PFS was not observed for OS. Improvement with ixazomib-Rd over placebo-Rd was observed in overall response (81.7% vs. 64.9%; odds ratio [OR], 2.38; p = 0.019) and complete response (22.5% vs. 3.9%; OR, 7.57; p < 0.001). Patient-reported quality of life and use of subsequent therapies were similar across treatment groups. No new safety concerns were identified. Compared with the main cohort, median OS was 10 months longer with ixazomib-Rd and 21 months shorter with placebo-Rd in this subgroup, indicating a clinically meaningful survival benefit of ixazomib-Rd treatment in this patient population with limited access to subsequent novel therapies.
摘要：
在TOURMALINE-MM1试验中，Ixazomib-来那度胺-地塞米松（ixazomib-Rd）在复发/难治性多发性骨髓瘤（MM）患者中显示优于安慰剂-Rd的临床疗效。超过85个月的中位随访时间，当患者显示疾病进展时，他们随后接受了新的治疗,这些治疗混淆了总生存期(OS)获益.这里,我们对来自七个被定义为新兴市场国家的148名患者进行了事后分析，在试验期间，MM获得新疗法的机会有限，描述这些疗法对OS的影响。患者被随机分配给ixazomib-Rd（n=71）或安慰剂-Rd（n=77）。中位无进展生存期（PFS）分别为18.7和10.2个月，艾沙佐米Rd与安慰剂Rd(风险比[HR]，0.504；p=0.008），证明了在主要试验中观察到的统计学上的显着改善。与安慰剂Rd相比，ixazomib-Rd的中位OS提高了32.6个月（63.5vs.30.9个月；HR，0.794；p=0.261)；然而，OS未观察到PFS的统计学显著获益.在总体反应中观察到Ixazomib-Rd相对于安慰剂-Rd的改善（81.7％vs.64.9%；赔率比[OR]，2.38；p=0.019）和完全反应（22.5%vs.3.9%；或，7.57；p<0.001）。患者报告的生活质量和后续治疗的使用在各治疗组相似。没有发现新的安全问题。与主要队列相比，在该亚组中，艾沙佐米Rd组的中位OS延长10个月，安慰剂Rd组的中位OS缩短21个月，表明在该患者人群中，ixazomib-Rd治疗具有临床意义的生存益处，而随后的新疗法的使用有限。
