Blood Cancer Journal ( IF 12.9 ) Pub Date : 2020-03-09 , DOI: 10.1038/s41408-020-0300-y Meletios A Dimopoulos 1 , Ruben Niesvizky 2 , Katja Weisel 3, 4 , David S Siegel 5 , Roman Hajek 6 , María-Victoria Mateos 7 , Michele Cavo 8 , Mei Huang 9 , Anita Zahlten-Kumeli 9 , Philippe Moreau 10
The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m2) and dexamethasone (once-weekly Kd70 mg/m2) improved progression-free survival compared with twice-weekly carfilzomib (27 mg/m2) and dexamethasone (twice-weekly Kd27 mg/m2) in patients with relapsed and refractory multiple myeloma (RRMM; median, 11.2 versus 7.6 months; hazard ratio [HR] = 0.69; 95% confidence interval, 0.54–0.88; P = 0.0029). Once-weekly dosing also improved response rates and depth of response. We performed a subgroup analysis from A.R.R.O.W. according to age (<65, 65–74, or ≥75 years), renal function (creatinine clearance <50, ≥50–<80, or ≥80 mL/min), number of prior therapies (2 or 3), and bortezomib-refractory status (yes or no). Compared with twice-weekly Kd27 mg/m2, once-weekly Kd70 mg/m2 reduced the risk of progression or death (HR = 0.60–0.85) and increased overall response rates in nearly all the examined subgroups, consistent with reports in the overall A.R.R.O.W. population. The safety profiles of once-weekly Kd70 mg/m2 across subgroups were also generally consistent with those in the overall population. Findings from this subgroup analysis generally demonstrate a favorable benefit–risk profile of once-weekly Kd70 mg/m2, further supporting once-weekly carfilzomib dosing as an appropriate treatment option for patients with RRMM, regardless of baseline patient and disease characteristics.
中文翻译:
根据选定的患者特征,每周一次与每周两次卡非佐米治疗复发性和难治性多发性骨髓瘤:3 期 ARROW 研究亚组分析
3 期 ARROW 研究表明,与每周两次卡非佐米 (27 mg/m 2 ) 相比,每周一次卡非佐米 (70 mg/m 2 )和地塞米松 (每周一次 Kd70 mg/m 2 )治疗可改善无进展生存期和地塞米松(每周两次 Kd27 mg/m 2)治疗复发难治性多发性骨髓瘤患者(RRMM;中位时间,11.2 个月与 7.6 个月;风险比 [HR] = 0.69;95% 置信区间,0.54–0.88;P = 0.0029 )。每周一次给药还可以提高反应率和反应深度。我们根据年龄(<65、65-74 或 ≥75 岁)、肾功能(肌酐清除率 <50、≥50-<80 或 ≥80 mL/min)、既往治疗次数从 ARROW 进行亚组分析(2 或 3),以及硼替佐米难治性状态(是或否)。与每周两次 Kd27 mg/m 2相比,每周一次 Kd70 mg/m 2降低了疾病进展或死亡的风险(HR = 0.60–0.85),并提高了几乎所有检查亚组的总体缓解率,这与ARROW 总体人口。各亚组每周一次 Kd70 mg/m 2的安全性也与总体人群的安全性基本一致。该亚组分析的结果通常表明每周一次 Kd70 mg/m 2具有良好的效益-风险特征,进一步支持每周一次卡非佐米给药作为 RRMM 患者的适当治疗选择,无论患者基线和疾病特征如何。