Costa Bruno Almeida, Costa Thomaz Alexandre, Chagas Gabriel Cavalcante Lima, Mouhieddine Tarek H, Richter Joshua, Usmani Saad Z, Mailankody Sham, Rajeeve Sridevi, Hashmi Hamza
Department of Medicine, Memorial Sloan Kettering Cancer Center, Myeloma and Cellular Therapy Service, New York, NY; Brookdale Department of Geriatrics and Palliative Medicine, The Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
Clin Lymphoma Myeloma Leuk. 2025 Jan;25(1):32-44. doi: 10.1016/j.clml.2024.09.008. Epub 2024 Sep 21.
The efficacy of elotuzumab, an anti-SLAMF7 monoclonal antibody, in treating relapsed/refractory multiple myeloma (RRMM) and newly-diagnosed multiple myeloma (NDMM) has varied in randomized controlled trials (RCTs). Moreover, there is limited data on its real-world application.
We conducted a systematic review and meta-analysis of RCTs investigating the addition of elotuzumab to backbone antimyeloma regimens. The primary outcome of interest was progression-free survival (PFS). Secondary efficacy outcomes included overall survival (OS), overall response rate (ORR), and rates of very good partial response or better (VGPR). Key toxicities were also evaluated.
Three RRMM trials (n = 915) and 5 NDMM trials (n = 1790) were included, with 50% of the 2705 patients receiving elotuzumab-containing triplets or quadruplets. In RRMM settings, elotuzumab use significantly improved PFS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.60-0.82; P < .001; I² = 0%). This benefit was consistent among patients with high-risk cytogenetics (HR, 0.62; 95% CI, 0.43-0.90; P = .01; I² = 0%) and was particularly evident in those previously treated with proteasome inhibitors (PIs) or immunomodulatory drugs (IMiDs). The RRMM cohort also demonstrated better OS, ORR, and ≥VGPR rate. However, the NDMM cohort showed no significant improvements in any efficacy outcomes. Despite an increase in severe (grade ≥3) infections, elotuzumab use did not adversely affect rates of severe cytopenias, severe cardiac disorders, or second primary malignancies.
Our results suggest that elotuzumab-containing regimens represent valuable therapeutic options for PI/IMiD-exposed patients with RRMM. In contrast, elotuzumab's role in frontline settings remains limited.
抗信号淋巴细胞激活分子家族成员7(SLAMF7)单克隆抗体埃罗妥珠单抗在治疗复发/难治性多发性骨髓瘤(RRMM)和新诊断的多发性骨髓瘤(NDMM)中的疗效在随机对照试验(RCT)中有所不同。此外,关于其实际应用的数据有限。
我们对研究将埃罗妥珠单抗添加到抗骨髓瘤主干方案中的随机对照试验进行了系统评价和荟萃分析。感兴趣的主要结局是无进展生存期(PFS)。次要疗效结局包括总生存期(OS)、总缓解率(ORR)以及非常好的部分缓解或更好缓解率(VGPR)。还评估了主要毒性。
纳入了3项RRMM试验(n = 915)和5项NDMM试验(n = 1790),2705例患者中有50%接受了含埃罗妥珠单抗的三联方案或四联方案。在RRMM环境中,使用埃罗妥珠单抗显著改善了PFS(风险比[HR],0.70;95%置信区间[CI],0.60 - 0.82;P < 0.001;I² = 0%)。这种益处在具有高危细胞遗传学特征的患者中是一致的(HR,0.62;95% CI,0.43 - 0.90;P = 0.01;I² = 0%),并且在先前接受蛋白酶体抑制剂(PIs)或免疫调节药物(IMiDs)治疗的患者中尤为明显。RRMM队列还显示出更好的OS、ORR和≥VGPR率。然而,NDMM队列在任何疗效结局方面均未显示出显著改善。尽管严重(≥3级)感染有所增加,但使用埃罗妥珠单抗并未对严重血细胞减少、严重心脏疾病或第二原发性恶性肿瘤的发生率产生不利影响。
我们的结果表明,含埃罗妥珠单抗的方案是RRMM中接受过PI/IMiD治疗患者的有价值治疗选择。相比之下,埃罗妥珠单抗在一线治疗中的作用仍然有限。