Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain.
University Hospital Ostrava and Faculty of Medicine, University of Ostrava 17, Ostrava, Czech Republic.
Clin Lymphoma Myeloma Leuk. 2024 Oct;24(10):703-714. doi: 10.1016/j.clml.2024.05.014. Epub 2024 May 19.
Preclinical studies suggest that combining nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, with pomalidomide/dexamethasone (Pd) with or without elotuzumab, an antisignaling lymphocytic activation molecule F7 monoclonal antibody, may improve multiple myeloma (MM) treatment efficacy.
The phase 3 CheckMate 602 study (NCT02726581) assessed the efficacy and safety of nivolumab plus pomalidomide/dexamethasone (NPd) and NPd plus elotuzumab (NE-Pd). Eligible patients (aged ≥ 18 years) had measurable MM after ≥ 2 prior lines of therapy, that included an immunomodulatory drug (IMiD) and proteasome inhibitor (PI), each for ≥ 2 consecutive cycles, alone or combined, and were refractory to their last line of therapy. Patients were randomized 3:3:1 to receive NPd, Pd, or NE-Pd. The primary endpoint was progression-free survival (PFS); overall response rate (ORR) was a key secondary endpoint.
At a median follow-up of 16.8 months, PFS was similar between treatment arms (Pd, 7.3 months [95% CI, 6.5-8.4]; NPd, 8.4 months [95% CI, 5.8-12.1]; NE-Pd, 6.3 months [95% CI, 2.4-11.1]). ORR was similar in the Pd (55%), NPd (48%), and NE-Pd (42%) arms. Nivolumab-containing arms were associated with a less favorable safety profile versus Pd, including a higher rate of thrombocytopenia (NPd, 25.0%; NE-Pd, 16.7%; Pd, 15.7%), any-grade immune-mediated adverse events (NPd, 13.9%; NE-Pd, 16.7%; Pd, 2.9%), and adverse events leading to discontinuation (NPd, 25.0%; NE-Pd, 33.3%; Pd, 18.6%). No new safety signals were identified.
CheckMate 602 did not demonstrate clinical benefit of nivolumab (+/- elotuzumab) plus Pd versus Pd for patients with relapsed/refractory MM (RRMM).
临床前研究表明，程序性死亡-1（PD-1）免疫检查点抑制剂纳武利尤单抗与泊马度胺/地塞米松（Pd）联合应用，或与抗信号淋巴细胞激活分子 F7 单克隆抗体埃罗妥珠单抗联合应用，可能改善多发性骨髓瘤（MM）的治疗效果。
这项 3 期 CheckMate 602 研究（NCT02726581）评估了纳武利尤单抗联合泊马度胺/地塞米松（NPd）和 NPd 联合埃罗妥珠单抗（NE-Pd）的疗效和安全性。符合条件的患者（年龄≥18 岁）在接受≥2 线治疗后出现可测量的 MM，其中包括免疫调节剂（IMiD）和蛋白酶体抑制剂（PI），每种药物均至少连续使用 2 个周期，单独或联合使用，且对末次治疗方案耐药。患者以 3:3:1 的比例随机分配接受 NPd、Pd 或 NE-Pd 治疗。主要终点为无进展生存期（PFS）；总缓解率（ORR）是关键次要终点。
中位随访 16.8 个月时，各治疗组的 PFS 无显著差异（Pd 组为 7.3 个月[95%CI，6.5-8.4]；NPd 组为 8.4 个月[95%CI，5.8-12.1]；NE-Pd 组为 6.3 个月[95%CI，2.4-11.1]）。Pd（55%）、NPd（48%）和 NE-Pd（42%）组的 ORR 相似。与 Pd 相比，纳武利尤单抗组的安全性较差，包括血小板减少症发生率较高（NPd 组为 25.0%，NE-Pd 组为 16.7%，Pd 组为 15.7%）、任何级别免疫介导的不良事件发生率较高（NPd 组为 13.9%，NE-Pd 组为 16.7%，Pd 组为 2.9%）以及导致停药的不良事件发生率较高（NPd 组为 25.0%，NE-Pd 组为 33.3%，Pd 组为 18.6%）。未发现新的安全性信号。
CheckMate 602 研究未显示纳武利尤单抗（±埃罗妥珠单抗）联合 Pd 对比 Pd 治疗复发/难治性多发性骨髓瘤（RRMM）患者的临床获益。
