达雷妥尤单抗单药治疗与泊马度胺联合低剂量地塞米松治疗多发性骨髓瘤的疗效比较：匹配调整间接比较。
Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison.
机构信息
Janssen Health Economics & Market Access EMEA Statistics & Modeling, Beerse, Belgium
Janssen Health Economics & Market Access EMEA, High Wycombe, United Kingdom.
出版信息
Oncologist. 2018 Mar;23(3):279-287. doi: 10.1634/theoncologist.2017-0103. Epub 2017 Nov 30.
BACKGROUND
Daratumumab (a human CD38-directed monoclonal antibody) and pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively new treatment options for patients with heavily pretreated multiple myeloma. A matching adjusted indirect comparison (MAIC) was used to compare absolute treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between the trial populations.
MATERIALS AND METHODS
The MAIC method reduces the risk of bias associated with naïve indirect comparisons. Data from 148 patients receiving daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared separately with data from patients receiving pomalidomide + LoDex in the MM-003 and STRATUS studies.
RESULTS
The MAIC-adjusted hazard ratio (HR) for OS of daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI], 0.38-0.83; = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; < .0001) for STRATUS. The treatment benefit was even more pronounced when the daratumumab population was restricted to pomalidomide-naïve patients (MM-003: HR, 0.33; 95% CI, 0.17-0.66; = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; = .0082). An additional analysis indicated a consistent trend of the OS benefit across subgroups based on M-protein level reduction (≥50%, ≥25%, and <25%).
CONCLUSION
The MAIC results suggest that daratumumab improves OS compared with pomalidomide + LoDex in patients with heavily pretreated multiple myeloma.
IMPLICATIONS FOR PRACTICE
This matching adjusted indirect comparison of clinical trial data from four studies analyzes the survival outcomes of patients with heavily pretreated, relapsed/refractory multiple myeloma who received either daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this method, daratumumab conferred a significant overall survival benefit compared with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head trials, these indirect comparisons provide useful insights to clinicians and reimbursement authorities around the relative efficacy of treatments.
背景
达雷妥尤单抗（一种靶向人 CD38 的单克隆抗体）和泊马度胺（一种免疫调节药物）联合地塞米松均为治疗经过大量预处理的多发性骨髓瘤患者的新的治疗选择。匹配调整间接比较（MAIC）用于比较达雷妥尤单抗与泊马度胺联合低剂量地塞米松（LoDex；40mg）治疗的绝对生存获益（OS），同时调整试验人群之间的差异。
材料与方法
MAIC 方法降低了与盲目间接比较相关的偏倚风险。来自 GEN501 和 SIRIUS 研究的 148 例接受达雷妥尤单抗（16mg/kg）治疗的患者的数据，分别与 MM-003 和 STRATUS 研究中接受泊马度胺联合 LoDex 治疗的患者的数据进行比较。
结果
在 MM-003 中，达雷妥尤单抗与泊马度胺联合 LoDex 的 OS 的 MAIC 调整后的危险比（HR）为 0.56（95%置信区间[CI]，0.38-0.83；=0.0041），在 STRATUS 中为 0.51（95% CI，0.37-0.69；<0.0001）。当将达雷妥尤单抗人群限制为泊马度胺初治患者时，治疗获益更加显著（MM-003：HR，0.33；95% CI，0.17-0.66；=0.0017；STRATUS：HR，0.41；95% CI，0.21-0.79；=0.0082）。一项额外的分析表明，根据 M 蛋白水平降低（≥50%、≥25%和<25%），OS 获益存在一致的趋势。
结论
MAIC 结果表明，与泊马度胺联合 LoDex 相比，达雷妥尤单抗可改善经过大量预处理的多发性骨髓瘤患者的 OS。
临床意义
本研究对四项研究的临床试验数据进行了匹配调整间接比较，分析了接受达雷妥尤单抗单药治疗或泊马度胺联合低剂量地塞米松治疗的大量预处理、复发/难治性多发性骨髓瘤患者的生存结局。使用这种方法，与泊马度胺联合低剂量地塞米松相比，达雷妥尤单抗显著改善了总体生存获益。在没有头对头试验的情况下，这些间接比较为临床医生和报销机构提供了有关治疗相对疗效的有用见解。
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