Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Kawasumi Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8602, Japan.
Department of Internal Medicine III, Division of Hematology and Cell Therapy, Yamagata University Graduate School of Medicine, Yamagata, Japan.
Jpn J Clin Oncol. 2024 Sep 4;54(9):991-1000. doi: 10.1093/jjco/hyae068.
Despite advances, most patients with multiple myeloma (MM) experience relapse and repeat multiple treatment lines, highlighting an unmet need for patients with relapsed or refractory MM (RRMM). Bispecific antibodies are a new option, but their efficacy and safety in Japanese patients are unknown.
This was an analysis of Japanese patients receiving elranatamab monotherapy in MagnetisMM-2 (NCT04798586) and MagnetisMM-3 (NCT04649359). Both studies evaluated a priming dose regimen of elranatamab followed by weekly subcutaneous doses, in patients with disease progression while receiving or who were intolerant to ≥3 prior therapies (≥1 proteasome inhibitor, ≥1 immunomodulatory drug and ≥1 anti-CD38 monoclonal antibody). The primary endpoints were dose limiting toxicities (DLTs) in MagnetisMM-2 and confirmed objective response rate (ORR) in MagnetisMM-3. In both, key secondary endpoints included safety, tolerability, duration of response, time to response, progression-free survival and overall survival.
In MagnetisMM-2 (N = 4) and MagnetisMM-3 (n = 12), median ages were 68.5 and 66.5 years, respectively. No DLTs were observed in MagnetisMM-2. ORRs were 50.0% (95% CI, 6.8-93.2) and 58.3% (95% CI, 27.7-84.8) in MagnetisMM-2 and MagnetisMM-3, respectively. All patients experienced treatment-emergent adverse events in MagnetisMM-2 (grade 3/4: 75.0%) and MagnetisMM-3 (grade 3/4: 100%); cytokine release syndrome occurred in 100% (grade 3/4: 25.0%) and 58.3% (no grade 3/4) of patients, respectively. Neither study reported immune effector cell-associated neurotoxicity syndrome.
No new safety signals were observed, and ORRs were similar to that of the overall MagnetisMM-3 trial population, supporting further studies of elranatamab in Japanese patients with RRMM. ClinicalTrials.gov identifier: NCT04798586 (MagnetisMM-2), NCT04649359 (MagnetisMM-3).
尽管取得了进展，但大多数多发性骨髓瘤（MM）患者会复发并多次接受治疗，这突显了复发或难治性 MM（RRMM）患者存在未满足的需求。双特异性抗体是一种新的选择，但它们在日本患者中的疗效和安全性尚不清楚。
这是一项对接受 Elranatamab 单药治疗的日本患者进行的分析，该分析来自 MagnetisMM-2（NCT04798586）和 MagnetisMM-3（NCT04649359）研究。两项研究均评估了 Elranatamab 的诱导剂量方案，随后每周皮下给药，用于疾病进展时正在接受治疗或不耐受≥3 种先前治疗（≥1 种蛋白酶体抑制剂、≥1 种免疫调节剂和≥1 种抗 CD38 单克隆抗体）的患者。主要终点是 MagnetisMM-2 中的剂量限制毒性（DLT）和 MagnetisMM-3 中的确认客观缓解率（ORR）。在这两项研究中，关键次要终点包括安全性、耐受性、缓解持续时间、反应时间、无进展生存期和总生存期。
在 MagnetisMM-2（N=4）和 MagnetisMM-3（n=12）中，中位年龄分别为 68.5 岁和 66.5 岁。在 MagnetisMM-2 中未观察到 DLT。ORR 分别为 50.0%（95%CI，6.8-93.2）和 58.3%（95%CI，27.7-84.8）。在 MagnetisMM-2 和 MagnetisMM-3 中，所有患者均出现治疗相关不良事件（3/4 级：75.0%）和 MagnetisMM-3（3/4 级：100%）；细胞因子释放综合征分别发生在 100%（3/4 级：25.0%）和 58.3%（无 3/4 级）的患者中。两项研究均未报告免疫效应细胞相关神经毒性综合征。
未观察到新的安全性信号，ORR 与 MagnetisMM-3 总体试验人群相似，支持进一步研究 Elranatamab 在日本 RRMM 患者中的应用。临床试验.gov 标识符：NCT04798586（MagnetisMM-2），NCT04649359（MagnetisMM-3）。
