David S. Siegel, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ; Meletios A. Dimopoulos, National and Kapodistrian University of Athens, Athens, Greece; Heinz Ludwig, Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria; Thierry Facon, Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire de Lille, Lille, France; Hartmut Goldschmidt, Heidelberg Medical University and National Center of Tumor Diseases, Heidelberg, Germany; Andrzej Jakubowiak, University of Chicago Medicine, Chicago, IL; Jesus San-Miguel, Clinica Universidad de Navarra-Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Pamplona, Spain; Mihaela Obreja and Julie Blaedel, Amgen, Thousand Oaks, CA; and A. Keith Stewart, Mayo Clinic, Scottsdale, AZ.
J Clin Oncol. 2018 Mar 10;36(8):728-734. doi: 10.1200/JCO.2017.76.5032. Epub 2018 Jan 17.
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.
在复发或难治性多发性骨髓瘤患者中接受卡非佐米、来那度胺和地塞米松（KRd）与来那度胺加地塞米松（Rd）治疗的 ASPIRE 研究中，卡非佐米组的无进展生存期（progression-free survival，PFS）显著改善（风险比，0.69；双侧 P <.001）。本次预设分析报告了最终的总生存期（overall survival，OS）数据和更新的安全性结果。
符合条件的患者为复发多发性骨髓瘤（既往接受过一线至三线治疗），按 1:1 比例随机分配，接受 28 天周期的 KRd 或 Rd 治疗，直至同意退出、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 治疗。PFS 是主要终点；OS 是关键次要终点。使用分层对数秩检验比较治疗组之间的 OS。
KRd 组的中位 OS 为 48.3 个月（95%CI，42.4 至 52.8 个月），Rd 组为 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；单侧 P =.0045）。在接受一线治疗的患者中，KRd 组的中位 OS 比 Rd 组长 11.4 个月；在接受≥二线治疗的患者中，KRd 组比 Rd 组长 6.5 个月。因不良事件（adverse events，AE）而停止治疗的发生率分别为 19.9%（KRd）和 21.5%（Rd）。≥3 级 AE 发生率分别为 87.0%（KRd）和 83.3%（Rd）。有意义的是，感兴趣的特定≥3 级 AE（分组术语；KRd 比 Rd）包括急性肾衰竭（3.8%比 3.3%）、心力衰竭（4.3%比 2.1%）、缺血性心脏病（3.8%比 2.3%）、高血压（6.4%比 2.3%）、造血血小板减少症（20.2%比 14.9%）和周围神经病（2.8%比 3.1%）。
KRd 与 Rd 相比，显著降低了死亡风险，使死亡风险降低了 7.9 个月，改善了生存。KRd 的疗效优势在首次复发时最为明显。
