Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Department of Hematology, Centre Hospitalier Universitaire, Université de Poitiers, Poitiers, France.
Leukemia. 2021 Feb;35(2):562-572. doi: 10.1038/s41375-020-0868-z. Epub 2020 May 23.
The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ≥2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ≥60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates.
这项名为 ICARIA-MM 的随机、3 期研究评估了伊沙妥昔单抗（Isa）联合泊马度胺和地塞米松（Pd）与 Pd 治疗复发/难治性多发性骨髓瘤且既往接受过≥2 线治疗的患者的疗效。这项预设的亚组分析评估了肾功能损害（RI；估计肾小球滤过率<60mL/min/1.73m²）患者的疗效。Isa 以 10mg/kg 剂量静脉输注，第 1 周期每周一次，随后的 28 天周期每 2 周一次。患者接受标准剂量的 Pd。RI 患者中，Isa-Pd 组的中位无进展生存期（PFS）为 9.5 个月（n=55），Pd 组为 3.7 个月（n=49；风险比[HR]0.50；95%置信区间[CI]，0.30-0.85）。无 RI 患者中，Isa-Pd 组的中位 PFS 为 12.7 个月（n=87），Pd 组为 7.9 个月（n=96；HR0.58；95%CI，0.38-0.88）。有和无 RI 的患者中，Isa-Pd 组的总缓解率（ORR）更高（56%和 68%），而 Pd 组分别为 25%和 43%。Isa-Pd 组完全肾脏缓解率为 71.9%（23/32），Pd 组为 38.1%（8/21）；分别有 31.3%（10/32）和 19.0%（4/21）的患者持续≥60 天。Isa 的药代动力学在亚组间相似，表明 RI 患者无需调整剂量。总之，Isa 联合 Pd 可改善 PFS、ORR 和肾脏缓解率。
