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含免疫调节方案治疗复发/难治性多发性骨髓瘤的疗效比较:一项网状Meta分析

A Comparison of the Efficacy of Immunomodulatory-containing Regimens in Relapsed/Refractory Multiple Myeloma: A Network Meta-analysis.

作者信息

Dimopoulos Meletios Athanasios, Kaufman Jonathan L, White Darrell, Cook Gordon, Rizzo Maria, Xu Yingxin, Fahrbach Kyle, Gaudig Maren, Slavcev Mary, Dearden Lindsay, Lam Annette

机构信息

National and Kapodistrian University of Athens, Athens, Greece.

Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.

出版信息

Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):163-173.e6. doi: 10.1016/j.clml.2017.12.011. Epub 2018 Jan 5.

Abstract

BACKGROUND

Previous network meta-analyses combined studies of immunomodulatory drug (IMiD)-containing and IMiD-free regimens, despite a lack of head-to-head randomized controlled trials to robustly link them. However, patients with relapsed or refractory multiple myeloma (RRMM) treated with IMiD-containing regimens differ from those treated with IMiD-free regimens, especially relating to treatment history, which is an important treatment-effect modifier requiring clinical consideration when evaluating the most appropriate subsequent treatment options. A need exists to separately assess the efficacy of treatment regimens for patients who are suitable candidates for IMiD-containing and IMiD-free regimens. The presented analyses will enable clinicians to assess the best regimens to use in patients suitable for IMiD-containing regimens.

MATERIALS AND METHODS

We used a Bayesian network meta-analysis to compare IMiD-containing regimens in patients with RRMM. Additionally, subgroup analyses were conducted stratified by previous therapy line, previous bortezomib therapy, and previous lenalidomide therapy.

RESULTS

The results indicated that triplet combinations are more effective than doublet combinations. Of the triplet combinations, daratumumab, lenalidomide, dexamethasone (DRd) was significantly better in improving progression-free survival in patients with RRMM than were other IMiD-containing regimens (lenalidomide, dexamethasone [Rd]: hazard ratio [HR], 0.37; carfilzomib, Rd: HR, 0.54; elotuzumab, Rd: HR, 0.54; ixazomib, Rd: HR, 0.50). Similar trends were observed for overall survival and overall response. DRd showed the greatest probability of being the best treatment for all clinical efficacy outcomes. The subgroup analyses results were consistent with the base-case results.

CONCLUSION

In patients with RRMM who are suitable for an IMiD-containing regimen, DRd showed clear advantages in survival and response outcomes compared with other IMiD-containing regimens.

摘要

背景

既往的网状Meta分析纳入了含免疫调节药物(IMiD)方案和不含IMiD方案的研究,尽管缺乏强有力的头对头随机对照试验来将二者紧密联系起来。然而,接受含IMiD方案治疗的复发或难治性多发性骨髓瘤(RRMM)患者与接受不含IMiD方案治疗的患者有所不同,尤其是在治疗史方面,而治疗史是一个重要的治疗效果修饰因素,在评估最合适的后续治疗方案时需要临床考虑。对于适合含IMiD方案和不含IMiD方案的患者,有必要分别评估治疗方案的疗效。本分析将使临床医生能够评估适合含IMiD方案患者的最佳治疗方案。

材料与方法

我们采用贝叶斯网状Meta分析来比较RRMM患者中含IMiD的方案。此外,还根据既往治疗线数、既往硼替佐米治疗和既往来那度胺治疗进行了亚组分析。

结果

结果表明,三联组合比双联组合更有效。在三联组合中,达雷妥尤单抗、来那度胺、地塞米松(DRd)在改善RRMM患者无进展生存期方面显著优于其他含IMiD方案(来那度胺、地塞米松[Rd]:风险比[HR],0.37;卡非佐米、Rd:HR,0.54;埃罗妥珠单抗、Rd:HR,0.54;伊沙佐米、Rd:HR,0.50)。总生存期和总缓解率也观察到类似趋势。DRd在所有临床疗效结局方面显示出最有可能成为最佳治疗方案。亚组分析结果与基础病例结果一致。

结论

在适合含IMiD方案的RRMM患者中,与其他含IMiD方案相比,DRd在生存和缓解结局方面显示出明显优势。

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