Department of Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy.
Biostatistic Unit, Regina Elena National Institute for Cancer Treatment and Research, Rome, Italy.
Clin Lymphoma Myeloma Leuk. 2019 Jul;19(7):423-430. doi: 10.1016/j.clml.2019.03.014. Epub 2019 Mar 23.
Patients with chronic lymphocytic leukemia (CLL) who achieve undetectable minimal residual disease (U-MRD) (ie, < 10 detectable leukemic cells in peripheral blood or bone marrow) have better outcomes than those with detectable MRD. To assess the magnitude of improvement of progression-free survival (PFS) or overall survival (OS) in patients who achieved U-MRD after upfront chemotherapy (CT) or chemo-immunotherapy (CIT), we conducted a systematic review and meta-analysis.
The screening process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. The search strategy yielded 365 records, including 22 articles assessed for eligibility.
Eleven studies comprising 2457 patients with CLL treated in upfront with CT or CIT were considered suitable for inclusion in the quantitative meta-analysis. Nine studies (n = 2088) provided data on the impact of MRD on PFS and 6 (n = 1234) on OS. MRD was the main endpoint in only 2 of these studies (n = 213). Tests of heterogeneity revealed significant differences among studies for PFS and OS, which highlights differences across studies. U-MRD status was associated with significantly better PFS overall (P < .001) and in patients who achieved conventional complete remission (P = .01). Regarding OS, U-MRD predicted longer OS globally (P < .001) but not in patients having achieved complete remission (P = .82).
U-MRD status after treatment with CT or CIT in newly diagnosed CLL is associated with long-term survival. These findings provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of CLL.
达到不可检测的微小残留疾病（U-MRD）（即外周血或骨髓中可检测到的白血病细胞<10 个）的慢性淋巴细胞白血病（CLL）患者比可检测到 MRD 的患者有更好的结局。为了评估在接受初始化疗（CT）或化疗免疫治疗（CIT）后达到 U-MRD 的患者无进展生存期（PFS）或总生存期（OS）改善的幅度，我们进行了系统评价和荟萃分析。
筛选过程遵循系统评价和荟萃分析的首选报告项目指南。搜索策略产生了 365 条记录，其中包括评估合格性的 22 篇文章。
11 项研究共纳入 2457 例接受初始 CT 或 CIT 治疗的 CLL 患者，被认为适合纳入定量荟萃分析。9 项研究（n=2088）提供了 MRD 对 PFS 的影响数据，6 项研究（n=1234）提供了 OS 的影响数据。这些研究中只有 2 项（n=213）将 MRD 作为主要终点。PFS 和 OS 的异质性检验显示研究之间存在显著差异，这突出了研究之间的差异。U-MRD 状态与总体 PFS 显著相关（P<0.001），与达到常规完全缓解的患者相关（P=0.01）。关于 OS，U-MRD 全球预测 OS 更长（P<0.001），但在达到完全缓解的患者中则不然（P=0.82）。
新诊断的 CLL 患者接受 CT 或 CIT 治疗后 U-MRD 状态与长期生存相关。这些发现为将 MRD 评估作为 CLL 临床试验的终点提供了定量证据支持。
