Lai Eunice, Soon Yu Yang, Lee Ainsley Ryan Yan Bin, Wong Shi Yin, Soekojo Cinnie Yentia, Ooi Melissa, Chng Wee Joo, de Mel Sanjay
Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.
Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore.
Blood Neoplasia. 2024 Sep 16;1(4):100042. doi: 10.1016/j.bneo.2024.100042. eCollection 2024 Dec.
Lenalidomide, ixazomib, and daratumumab have been proposed as maintenance therapies for patients with newly diagnosed multiple myeloma (MM; NDMM). There are, however, no randomized controlled trials (RCTs) comparing them. We conducted a network meta-analysis (NMA) of RCTs comparing these agents against placebo in NDMM. A Bayesian NMA model was used to assess the relative effects of competing treatments on progression-free survival (PFS) and overall survival (OS) in 9 studies including 4115 patients with transplant-eligible MM (TEMM) and 1689 patients with non-transplant-eligible MM (NTEMM). Lenalidomide and daratumumab but not ixazomib were associated with improved PFS compared with placebo in patients with TEMM (lenalidomide [hazard ratio (HR), 0.46; 95% credible interval (CrI), 0.36-0.56]; daratumumab [HR, 0.49; 95% Crl, 0.32-0.76]; and ixazomib [HR, 0.72; 95% CrI, 0.46-1.12]) and those with NTEMM (lenalidomide [HR, 0.46; 95% CrI, 0.29-0.75] and ixazomib [HR, 0.69; 95% CrI, 0.43-1.18]). The PFS benefit for daratumumab was present regardless of whether daratumumab-based induction therapy was received. None of the agents showed an OS benefit, and PFS benefits were not seen in patients with high-risk cytogenetics. Lenalidomide was associated with second malignancies, ixazomib with thrombocytopenia, and daratumumab with pneumonia. We propose that lenalidomide remains the maintenance therapy of choice for NDMM.
来那度胺、伊沙佐米和达雷妥尤单抗已被提议作为新诊断多发性骨髓瘤（MM；NDMM）患者的维持治疗药物。然而，尚无随机对照试验（RCT）对它们进行比较。我们对RCT进行了一项网状Meta分析（NMA），比较这些药物与安慰剂在NDMM中的疗效。采用贝叶斯NMA模型评估9项研究中竞争治疗对无进展生存期（PFS）和总生存期（OS）的相对影响，这些研究包括4115例适合移植的MM（TEMM）患者和1689例不适合移植的MM（NTEMM）患者。与安慰剂相比，来那度胺和达雷妥尤单抗而非伊沙佐米与TEMM患者PFS改善相关（来那度胺[风险比（HR），0.46；95%可信区间（CrI），0.36 - 0.56]；达雷妥尤单抗[HR，0.49；95% CrI，0.32 - 0.76]；伊沙佐米[HR，0.72；95% CrI，0.46 - 1.12]）以及NTEMM患者（来那度胺[HR，0.46；95% CrI，0.29 - 0.75]和伊沙佐米[HR，0.69；95% CrI，0.43 - 1.18]）。无论是否接受基于达雷妥尤单抗的诱导治疗，达雷妥尤单抗均有PFS获益。这些药物均未显示出OS获益，高危细胞遗传学患者也未观察到PFS获益。来那度胺与第二原发性恶性肿瘤相关，伊沙佐米与血小板减少相关，达雷妥尤单抗与肺炎相关。我们建议来那度胺仍是NDMM维持治疗的首选药物。
