CHRU Lille Hôpital Claude Huriez, Lille, France.
Gachon University Gil Medical Center, Seongnam-si, Korea.
Blood. 2019 May 2;133(18):1953-1963. doi: 10.1182/blood-2018-09-874396. Epub 2019 Feb 28.
The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m: C1D1, C1D2; 36 mg/m thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m) and prednisone (60 mg/m) were administered on D1-4. The primary endpoint was progression-free survival (PFS). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n = 478; VMP, n = 477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; = .159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease-negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 peripheral neuropathy was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. This trial was registered at www.clinicaltrials.gov as #NCT01818752.
CLARION 研究的第 3 阶段比较了卡非佐米-马法兰-泼尼松（KMP）与硼替佐米-马法兰-泼尼松（VMP）在不适合移植的新诊断多发性骨髓瘤（NDMM）患者中的疗效。患者按 1:1 随机分配至 KMP 或 VMP 组，接受 9 个 42 天周期（C）的治疗。患者接受卡非佐米治疗，第 1、2、8、9、22、23、29、30 天（20 mg/m：C1D1，C1D2；此后 36 mg/m）或硼替佐米治疗，第 1、4、8、11、22、25、29、32 天（1.3 mg/m：C5-9 周期中第 4、11、25、32 天省略）。马法兰（9 mg/m）和泼尼松（60 mg/m）在第 1-4 天给予。主要终点是无进展生存期（PFS）。955 例患者被随机分组（意向治疗人群：KMP 组，n=478；VMP 组，n=477）。KMP 组的中位 PFS 为 22.3 个月，VMP 组为 22.1 个月（风险比[HR]，0.906；95%置信区间[CI]，0.746-1.101；P=0.159）。两组的中位总生存期相似，均未达到（HR，1.08；95%CI，0.82-1.43）。KMP 组的总缓解率为 84.3%，VMP 组为 78.8%。完全缓解率 KMP 组为 25.9%，VMP 组为 23.1%。微小残留病灶阴性率 KMP 组为 15.7%（KMP），VMP 组为 15.5%（VMP）。KMP 组中发生率高于 VMP 组≥5%的患者的有兴趣的不良事件（任何级别）为急性肾衰竭（13.9%[KMP] vs 6.2%[VMP]）和心力衰竭（10.8% vs 4.3%）。≥3 级不良事件发生率为 74.7%（KMP）和 76.2%（VMP）。KMP 组的≥2 级周围神经病变发生率低于 VMP 组（2.5% vs 35.1%）。CLARION 研究中 KMP 治疗在统计学上并未显著改善与 VMP 相比的 PFS。该试验在 www.clinicaltrials.gov 上注册，编号为#NCT01818752。
