Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Veterans Administration Boston Healthcare System, West Roxbury, MA.
Blood Adv. 2020 Dec 8;4(23):5988-5999. doi: 10.1182/bloodadvances.2020002827.
The prognostic value of minimal residual disease (MRD) for progression-free survival (PFS) and overall survival (OS) was evaluated in a large cohort of patients with multiple myeloma (MM) using a systematic literature review and meta-analysis. Medline and EMBASE databases were searched for articles published up to 8 June 2019, with no date limit on the indexed database. Clinical end points stratified by MRD status (positive or negative) were extracted, including hazard ratios (HRs) on PFS and OS, P values, and confidence intervals (CIs). HRs were estimated based on reconstructed patient-level data from published Kaplan-Meier curves. Forty-four eligible studies with PFS data from 8098 patients, and 23 studies with OS data from 4297 patients were identified to assess the association between MRD status and survival outcomes. Compared with MRD positivity, achieving MRD negativity improved PFS (HR, 0.33; 95% CI, 0.29-0.37; P < .001) and OS (HR, 0.45; 95% CI, 0.39-0.51; P < .001). MRD negativity was associated with significantly improved survival outcomes regardless of disease setting (newly diagnosed or relapsed/refractory MM), MRD sensitivity thresholds, cytogenetic risk, method of MRD assessment, depth of clinical response at the time of MRD measurement, and MRD assessment premaintenance and 12 months after start of maintenance therapy. The strong prognostic value of MRD negativity and its association with favorable outcomes in various disease and treatment settings sets the stage to adopt MRD as a treatment end point, including development of therapeutic strategies. This large meta-analysis confirms the utility of MRD as a relevant surrogate for PFS and OS in MM.
采用系统文献回顾和荟萃分析，在使用大量多发性骨髓瘤（MM）患者评估微小残留病（MRD）对无进展生存（PFS）和总生存（OS）的预后价值。在截止到 2019 年 6 月 8 日的文献中，检索了 Medline 和 EMBASE 数据库，索引数据库没有时间限制。提取了按 MRD 状态（阳性或阴性）分层的临床终点，包括 PFS 和 OS 的危险比（HR）、P 值和置信区间（CI）。HR 是根据发表的 Kaplan-Meier 曲线的重建患者水平数据估计的。有 44 项研究符合条件，这些研究提供了 8098 例患者的 PFS 数据，有 23 项研究提供了 4297 例患者的 OS 数据，以评估 MRD 状态与生存结局之间的关系。与 MRD 阳性相比，达到 MRD 阴性可改善 PFS（HR，0.33；95%CI，0.29-0.37；P<0.001）和 OS（HR，0.45；95%CI，0.39-0.51；P<0.001）。MRD 阴性与生存结局显著改善相关，而与疾病状态（新诊断或复发/难治性 MM）、MRD 敏感性阈值、细胞遗传学风险、MRD 评估方法、MRD 测量时临床缓解的深度以及维持治疗开始前和 12 个月后的 MRD 评估无关。MRD 阴性具有很强的预后价值，并且与各种疾病和治疗环境中的良好结局相关，为将 MRD 作为治疗终点（包括开发治疗策略）奠定了基础。这项大型荟萃分析证实了 MRD 作为 MM 中 PFS 和 OS 的相关替代指标的实用性。
