背景:尽管有进步,大多数多发性骨髓瘤(MM)患者经历复发和重复多个治疗线,强调对复发性或难治性MM(RRMM)患者的需求未得到满足。双特异性抗体是一种新的选择,但其在日本患者中的疗效和安全性尚不清楚。
方法:这是对日本患者进行的分析,这些患者接受依拉那他单抗在MagnetisMM-2(NCT04798586)和MagnetisMM-3(NCT04649359)中的单药治疗。两项研究都评估了依拉那他单抗的启动剂量方案,然后每周皮下剂量。在接受或不耐受≥3种先前疗法(≥1种蛋白酶体抑制剂,≥1种免疫调节药物和≥1种抗CD38单克隆抗体)。主要终点是磁MM-2中的剂量限制性毒性(DLTs)和磁MM-3中确认的客观反应率(ORR)。在两者中,关键的次要终点包括安全性,耐受性,响应的持续时间,响应时间,无进展生存期和总生存期。
结果:在磁性MM-2(N=4)和磁性MM-3(n=12)中,平均年龄分别为68.5岁和66.5岁,分别。在磁MM-2中未观察到DLT。磁性MM-2和磁性MM-3的ORR分别为50.0%(95%CI,6.8-93.2)和58.3%(95%CI,27.7-84.8)。所有患者均出现因治疗引起的不良事件,分别出现在MagnetisMM-2(3/4级:75.0%)和MagnetisMM-3(3/4级:100%);细胞因子释放综合征发生在100%(3/4级:25.0%)和58.3%(无3/4级)患者中。分别。两项研究均未报道免疫效应细胞相关神经毒性综合征。
结论:没有观察到新的安全性信号,ORR与整个MagnetisMM-3试验人群相似,支持Elranatamab在日本RRMM患者中的进一步研究。ClinicalTrials.gov标识符:NCT04798586(MagnetisMM-2),NCT04649359(磁性MM-3)。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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).