Costa Luciano J, LeBlanc Thomas W, Tesch Hans, Sonneveld Pieter, Johnson Sarasa M A, Vekeman Francis, Hlavacek Patrick, Meche Aster, Kim Chai Hyun, Cislo Paul, Hughes David M, Nador Guido, DiBonaventura Marco
University of Alabama at Birmingham, Birmingham, AL, USA.
Duke University School of Medicine, Durham, NC, USA.
Blood Lymphat Cancer. 2025 Jun 5;15:11-20. doi: 10.2147/BLCTT.S516356. eCollection 2025.
Elranatamab is a BCMAxCD3 bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma (RRMM). The registrational Phase 2 MagnetisMM-3 (NCT04649359) trial was single-armed; the aim of this indirect comparison was to contextualize the efficacy of the most recent 28.4-month follow-up data cut from this trial, allowing for more mature data, with real-world data serving as an external control.
We conducted a retrospective cohort study to indirectly compare the efficacy observed in the elranatamab arm of MagnetisMM-3 Cohort A (BCMA-naïve; N=123) from the March 26, 2024 data cut with COTA, a US-based oncology electronic health record database, as an external control. All MM patients with triple-class refractory disease who initiated a new line of therapy (representing real-world physician's choice) between November 2015 and August 2023 in the COTA database were included. MagnetisMM-3 inclusion (eg, ≥18 years, measurable disease within 90 days of the index, Eastern Cooperative Oncology Group [ECOG] ≤ 2) and exclusion criteria (eg, plasma cell leukemia, smoldering MM) were applied to obtain comparable patient populations across sources. The elranatamab cohort was compared with the physician's choice cohort on progression-free survival (PFS), overall survival (OS), and duration of response (DOR) using Cox proportional hazard models implementing inverse probability of treatment weighting to adjust for any remaining imbalances on confounding variables.
N=123 patients treated with elranatamab were compared with 577 patients treated with real-world physicians' choice of therapy. Compared with physician's choice, elranatamab significantly improved PFS (HR = 0.38 [0.22, 0.65], p<0.05), OS (HR = 0.58 [0.35, 0.96], p<0.05), and DOR (HR = 0.16 [0.07, 0.34], p<0.05).
In this comparison of patients from the MagnetisMM-3 trial and real-world patients who resemble those from the trial, patients treated with elranatamab exhibited significantly better clinical outcomes compared with treatments currently used in real-world clinical practice.
埃拉纳单抗是一种获批用于治疗复发/难治性多发性骨髓瘤(RRMM)的BCMAxCD3双特异性抗体。注册性2期MagnetisMM-3(NCT04649359)试验为单臂试验;本次间接比较的目的是将该试验最近一次28.4个月随访数据截止时的疗效置于实际背景中,以便获得更成熟的数据,将真实世界数据作为外部对照。
我们进行了一项回顾性队列研究,以间接比较MagnetisMM-3队列A(初治BCMA;N = 123)的埃拉纳单抗治疗组在2024年3月26日数据截止时观察到的疗效与美国肿瘤电子健康记录数据库COTA作为外部对照的疗效。纳入了2015年11月至2023年8月在COTA数据库中开始新一线治疗(代表真实世界医生的选择)的所有三重耐药性疾病的MM患者。应用MagnetisMM-3的纳入标准(如≥18岁,入组后90天内可测量疾病,东部肿瘤协作组[ECOG]≤2)和排除标准(如浆细胞白血病、冒烟型MM)以获得不同来源间可比的患者群体。使用实施治疗权重逆概率的Cox比例风险模型,在无进展生存期(PFS)、总生存期(OS)和缓解持续时间(DOR)方面,将埃拉纳单抗队列与医生选择队列进行比较,以调整混杂变量上的任何剩余不平衡。
将123例接受埃拉纳单抗治疗的患者与577例接受真实世界医生选择治疗的患者进行比较。与医生选择的治疗相比,埃拉纳单抗显著改善了PFS(风险比[HR]=0.38[0.22,0.65],p<0.05)、OS(HR = 0.58[0.35,0.96])和DOR(HR = 0.16[0.07,0.34],p<0.05)。
在本次对MagnetisMM-3试验患者与类似试验患者的真实世界患者的比较中,与目前真实世界临床实践中使用的治疗方法相比,接受埃拉纳单抗治疗的患者表现出显著更好的临床结局。