Facon Thierry, Niesvizky Ruben, Mateos Maria-Victoria, Siegel David, Rosenbaum Cara, Bringhen Sara, Weisel Katja, Ho P Joy, Ludwig Heinz, Kumar Shaji, Wang Kenneth, Obreja Mihaela, Yang Zhao, Klippel Zandra, Mezzi Khalid, Goldrick Amanda, Tekle Christina, Dimopoulos Meletios A
Hôpital Claude Huriez, Lille, France.
Weill Cornell Medicine, New York, NY.
Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.
Frailty is most prevalent among elderly multiple myeloma (MM) patients, and frail patients have a higher risk of poor outcomes due to reduced performance status or comorbidities. This post hoc analysis assessed efficacy and safety of carfilzomib combinations in frail patients with relapsed and/or refractory MM from the phase 3 ASPIRE (carfilzomib [27 mg/m2]-lenalidomide-dexamethasone [KRd27] vs lenalidomide-dexamethasone [Rd]), ENDEAVOR (carfilzomib [56 mg/m2]-dexamethasone [Kd56] vs bortezomib-dexamethasone [Vd]), and ARROW (once-weekly carfilzomib [70 mg/m2]-dexamethasone [Kd70] vs carfilzomib [27 mg/m2]-dexamethasone [Kd27]) studies. A frailty algorithm incorporating age, Charlson comorbidity index, and performance status classified patients as fit, intermediate, or frail. Results are presented for frail patients (ASPIRE, n = 196; ENDEAVOR, n = 330; ARROW, n = 141). In ASPIRE, median progression-free survival (PFS) (hazard ratio; 95% confidence interval) was 24.1 (KRd27) vs 15.9 months (Rd) (0.78; 0.54-1.12); median overall survival (OS) was 36.4 vs 26.2 months (0.79; 0.57-1.08). In ENDEAVOR, median PFS was 18.7 (Kd56) vs 6.6 months (Vd) (0.50; 0.36-0.68); median OS was 33.6 vs 21.8 months (0.75; 0.56-1.00). In ARROW, median PFS was 10.3 (once-weekly Kd70) vs 6.6 months (twice-weekly Kd27) (0.76; 0.49-1.16). In all 3 studies, rates of grade ≥3 treatment-emergent adverse events were consistent with those observed in the primary studies. The ASPIRE, ENDEAVOR, and ARROW primary analyses demonstrated favorable benefit-risk profiles with carfilzomib-containing regimens compared with controls. Across clinically relevant subgroups, including those by frailty status, consistent efficacy and safety were observed with KRd27, Kd56, and weekly Kd70, and treatment with these regimens should not be restricted by frailty status.
衰弱在老年多发性骨髓瘤（MM）患者中最为普遍，由于身体机能下降或合并症，衰弱患者预后不良的风险更高。这项事后分析评估了来自3期ASPIRE（卡非佐米[27mg/m²]-来那度胺-地塞米松[KRd27]对比来那度胺-地塞米松[Rd]）、ENDEAVOR（卡非佐米[56mg/m²]-地塞米松[Kd56]对比硼替佐米-地塞米松[Vd]）和ARROW（每周一次卡非佐米[70mg/m²]-地塞米松[Kd70]对比卡非佐米[27mg/m²]-地塞米松[Kd27]）研究中卡非佐米联合方案在复发和/或难治性MM衰弱患者中的疗效和安全性。一种结合年龄、查尔森合并症指数和身体机能状态的衰弱算法将患者分为健康、中等或衰弱。给出了衰弱患者的结果（ASPIRE，n = 196；ENDEAVOR，n = 330；ARROW，n = 141）。在ASPIRE中，中位无进展生存期（PFS）（风险比；95%置信区间）为24.1（KRd27）对比15.9个月（Rd）（0.78；0.54 - 1.12）；中位总生存期（OS）为36.4对比26.2个月（0.79；0.57 - 1.08）。在ENDEAVOR中，中位PFS为18.7（Kd56）对比6.6个月（Vd）（0.50；0.36 - 0.68）；中位OS为33.6对比21.8个月（0.75；0.56 - 1.00）。在ARROW中，中位PFS为10.3（每周一次Kd70）对比6.6个月（每周两次Kd27）（0.76；0.49 - 1.16）。在所有3项研究中，≥3级治疗中出现的不良事件发生率与主要研究中观察到的一致。ASPIRE、ENDEAVOR和ARROW的主要分析表明，与对照组相比，含卡非佐米的方案具有良好的获益风险特征。在包括衰弱状态在内的临床相关亚组中，观察到KRd27、Kd56和每周一次Kd70具有一致的疗效和安全性，不应因衰弱状态而限制使用这些方案进行治疗。
