Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥ 3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse.

中文翻译：

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使用卡非佐米、来那度胺和地塞米松改善复发或难治性多发性骨髓瘤患者的总体生存率

目的在卡非佐米、来那度胺和地塞米松 (KRd) 与来那度胺加地塞米松 (Rd) 治疗复发性或难治性多发性骨髓瘤患者的 ASPIRE 研究中，卡非佐米组的无进展生存期显着提高（风险比，0.69；两侧 P < .001）。这项预先指定的分析报告了最终的总生存 (OS) 数据和更新的安全性结果。患者和方法 患有复发性多发性骨髓瘤的成人（1 到 3 个先前的治疗线）符合条件并以 1 比 1 的比例随机分配接受 KRd 或 Rd，以 28 天为周期，直到撤回同意、疾病进展或发生不可接受的毒性。18 个周期后，所有患者仅接受 Rd。无进展生存期是主要终点；OS 是一个关键的次要终点。使用分层对数秩检验比较治疗组之间的 OS。结果 KRd 的中位 OS 为 48.3 个月（95% CI，42.4 至 52.8 个月），而 Rd 的中位 OS 为 40.4 个月（95% CI，33.6 至 44.4 个月）（风险比，0.79；95% CI，0.67 至 0.95；片面） P = .0045）。在接受一种先前治疗的患者中，KRd 的中位 OS 比 Rd 长 11.4 个月；在接受≥ 两种先前治疗的患者中，KRd 比 Rd 长 6.5 个月。由于不良事件 (AE) 导致的治疗中断率为 19.9% (KRd) 和 21.5% (Rd)。≥ 3 级 AE 率为 87.0% (KRd) 和 83.3% (Rd)。选定的 ≥ 3 级 AE（分组术语；KRd 与 Rd）包括急性肾功能衰竭（3.8% 对 3.3%）、心力衰竭（4.3% 对 2.1%）、缺血性心脏病（3.8% 对 2.3%）、高血压（ 6.4% 对 2.3%），造血性血小板减少症（20. 2% 对 14.9%）和周围神经病变（2.8% 对 3.1%）。结论 与 Rd 相比，KRd 显示出具有统计学意义和临床意义的死亡风险降低，将生存期提高了 7.9 个月。KRd 疗效优势在首次复发时最为明显。