Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, KS.
Department of Internal Medicine, The University of Kansas Medical Center, Kansas City, KS.
Clin Lymphoma Myeloma Leuk. 2021 Jul;21(7):489-496. doi: 10.1016/j.clml.2021.03.006. Epub 2021 Mar 26.
Lenalidomide use in nearly all induction regimens for multiple myeloma (MM) has led to the treatment of lenalidomide-refractory disease becoming one of the most important clinical questions in its treatment. Given the lack of direct comparisons of treatment regimens for lenalidomide-refractory MM, we used a systematic review to identify randomized controlled trials (RCTs) that included lenalidomide-refractory subgroup analysis.
We performed a systematic review to identify RCTs for MM that enrolled patients with lenalidomide-refractory disease, then performed a network meta-analysis (NMA) using random effects model to compare regimens.
We identified 123 discrete RCTs, of which 7 reported primary outcomes for lenalidomide-refractory MM. These were linked in 2 discrete networks totaling 1698 lenalidomide-refractory patients. Network 1 compared bortezomib (bort)/dexamethasone (dex) versus other treatments, and analysis showed triplet therapy with pomalidomide (pom)/bort/dex (hazard ratios [HR] 0.65, 95% confidence interval [CI], 0.50-0.84), daratumumab (dara)/bort/dex (HR 0.36, 95% CI, 0.21-0.63), and dara/carfilzomib (carf)/dex (HR 0.38, 95% CI, 0.21-0.69) as more effective than bort/dex. Network 2 compared dex versus other treatments, and analysis showed pom/dex (HR 0.50, 95% CI, 0.40-0.62), isatuximab (isa)/pom/dex (HR 0.30, 95% CI, 0.20-0.44), and elotuzumab (elo)/pom/dex (HR 0.27, 95% CI, 0.16-0.45) as more effective than dex. Within each network, monoclonal antibody (mAb)-containing regimens had lower HRs and higher P-scores than non-mAb regimens, indicating higher likelihood of these regimens being most efficacious.
The results of our NMA demonstrated that for lenalidomide-refractory MM, triplet therapy containing mAbs are superior. There is need for further RCTs to better ascertain the best standard of care for these patients.
来那度胺几乎用于多发性骨髓瘤（MM）的所有诱导治疗方案中，导致来那度胺难治性疾病的治疗成为其治疗中最重要的临床问题之一。鉴于来那度胺难治性 MM 的治疗方案缺乏直接比较，我们使用系统评价来确定包含来那度胺难治性亚组分析的随机对照试验（RCT）。
我们进行了一项系统评价，以确定纳入来那度胺难治性疾病患者的 MM RCT，然后使用随机效应模型进行网络荟萃分析（NMA）以比较方案。
我们确定了 123 项离散 RCT，其中 7 项报告了来那度胺难治性 MM 的主要结局。这些 RCT 链接成两个包含 1698 名来那度胺难治性患者的离散网络。网络 1 比较硼替佐米（bort）/地塞米松（dex）与其他治疗方法，分析显示来那度胺难治性患者使用泊马度胺（pom）/硼替佐米（bort）/地塞米松（dex）（危险比 [HR]0.65，95%置信区间 [CI]0.50-0.84）、达雷妥尤单抗（dara）/硼替佐米（bort）/地塞米松（dex）（HR0.36，95%CI0.21-0.63）和 dara/卡非佐米（carf）/地塞米松（dex）（HR0.38，95%CI0.21-0.69）的疗效优于 bort/dex。网络 2 比较地塞米松与其他治疗方法，分析显示来那度胺难治性患者使用泊马度胺（pom）/地塞米松（dex）（HR0.50，95%CI0.40-0.62）、伊沙佐米（isa）/泊马度胺（pom）/地塞米松（dex）（HR0.30，95%CI0.20-0.44）和依鲁替尼（elo）/泊马度胺（pom）/地塞米松（dex）（HR0.27，95%CI0.16-0.45）的疗效优于地塞米松。在每个网络中，含有单克隆抗体（mAb）的治疗方案的 HR 较低，P 评分较高，表明这些方案更有效。
我们的 NMA 结果表明，对于来那度胺难治性 MM，含有 mAb 的三联疗法更为有效。需要进一步的 RCT 来更好地确定这些患者的最佳标准治疗方法。
