Cedars-Sinai Medical Center, Los Angeles, California, USA.
Mayo Clinic, Rochester, Minnesota, USA.
Am J Hematol. 2020 Dec;95(12):1486-1494. doi: 10.1002/ajh.25963. Epub 2020 Sep 5.
Daratumumab in combination with lenalidomide-dexamethasone (D-Rd) recently received FDA approval for the treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression-free survival (PFS) in patients treated with D-Rd in the MAIA trial and patients treated with common standard-of-care regimens from the Flatiron Health electronic health record-derived deidentified database, which has data from patients treated primarily at community-based oncology practices in the United States. Individual-level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D-Rd to bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-dexamethasone (Vd); lenalidomide-dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D-Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D-Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity-score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D-Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D-Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head-to-head trials comparing D-Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant-ineligible patients with NDMM.
达雷妥尤单抗与来那度胺-地塞米松（D-Rd）联合治疗新诊断多发性骨髓瘤（NDMM）的无移植资格患者，最近获得了 FDA 批准。本 PEGASUS 研究比较了 MAIA 试验中接受 D-Rd 治疗的患者与来自 Flatiron Health 电子健康记录衍生的匿名数据库的常见标准治疗方案的患者的无进展生存期（PFS），该数据库的数据来自美国主要在社区肿瘤实践中接受治疗的患者。来自两个数据源的个体患者数据均用于进行 D-Rd 与硼替佐米-来那度胺-地塞米松（VRd）和硼替佐米-地塞米松（Vd）的锚定间接治疗比较（ITC）；ITC 的共同锚定为来那度胺-地塞米松（Rd）。反映 MAIA 内（D-Rd 与 Rd）和 Flatiron Health（VRd 与 Rd；Vd 与 Rd）PFS 直接比较的风险比（HR）分别用于进行 D-Rd 与 VRd 和 Vd 的 ITC。在应用 MAIA 纳入/排除标准和倾向评分加权后，Flatiron Health 患者在测量的基线特征上与 MAIA 试验人群相似。基于 MAIA 内的直接比较，与 Rd 相比，D-Rd 治疗与进展或死亡风险显著降低相关（HR 0.54；95%CI 0.42，0.71）。基于 ITC，与 Rd 相比，D-Rd 与进展或死亡风险显著降低相关（HR 0.68；95%CI 0.48，0.98）和 Vd（HR 0.48；95%CI 0.33，0.69）。在没有头对头比较 D-Rd 与 VRd 或 Vd 的试验的情况下，本 ITC 可能有助于为无移植资格的 NDMM 患者的治疗选择提供信息。
