Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Ann Hematol. 2021 Feb;100(2):405-419. doi: 10.1007/s00277-020-04316-8. Epub 2020 Oct 29.
Despite the increasing inclusion of novel agents within the multiple myeloma (MM) treatment sequence, their role for posttransplant consolidation therapy remains unclear. We systematically reviewed studies evaluating the efficacy of novel agent consolidation. We identified 11 citations on 12 prospective comparative studies, and 5 citations were single-arm or comparative studies with preliminary results. Nine different regimens were evaluated in 5905 patients. Risk assessment yielded serious risk of bias and heterogeneity across study designs was high. Irrespective of the regimen, deepened responses after consolidation were seen and improvements were more pronounced with multi-agent consolidation. Bortezomib, thalidomide, and dexamethasone improved long-term survival versus duplet consolidation, including in patients with high-risk cytogenetics. The addition of daratumumab to triplet regimens yielded modestly improved responses with significantly increased rates of minimal residual disease negativity but survival results were limited by short follow-up. In high-risk MM, responses were not different, whereas progression-free survival appeared to be improved with consolidation therapy, challenging the association of response and overall outcome in this subgroup. Our findings highlight the necessity of longer follow-up and consistent reporting to ensure comparability of studies to enable better evidence assessment and to identify patients benefitting from consolidation therapy.
尽管新型药物在多发性骨髓瘤(MM)治疗序贯中不断被纳入,但它们在移植后巩固治疗中的作用仍不清楚。我们系统地回顾了评估新型药物巩固治疗疗效的研究。我们在 12 项前瞻性比较研究中确定了 11 篇文献,其中 5 篇为初步结果的单臂或比较研究。在 5905 名患者中评估了 9 种不同的方案。风险评估存在严重的偏倚风险,研究设计之间的异质性很高。无论方案如何,巩固治疗后均能看到更深入的反应,并且多药物联合巩固治疗的效果更为显著。硼替佐米、沙利度胺和地塞米松与双联巩固治疗相比可改善长期生存,包括高危细胞遗传学患者。在三联方案中加入达雷妥尤单抗可适度改善缓解率,微小残留病灶阴性率显著增加,但由于随访时间短,生存结果有限。在高危 MM 中,缓解率无差异,但巩固治疗可改善无进展生存期,这对该亚组中缓解与总体结局的相关性提出了挑战。我们的研究结果强调了需要更长时间的随访和一致的报告,以确保研究的可比性,从而能够更好地评估证据,并确定受益于巩固治疗的患者。