Minimal Residual Disease and Survival Outcomes in Patients With Chronic Lymphocytic Leukemia: A Systematic Review and Meta-analysis

To assess the magnitude of improvement of progression-free survival or overall survival in patients who achieved undetectable minimal residual disease (MRD) after upfront chemotherapy or chemo-immunotherapy, we conducted a systematic review and meta-analysis. Nine studies (n = 2088) provided data on the impact of MRD on progression-free survival and 6 (n = 1234) on overall survival. Results confirm that undetectable MRD status after treatment with chemotherapy or chemo-immunotherapy in newly diagnosed chronic lymphocytic leukemia is associated with long-term survival. Background: Patients with chronic lymphocytic leukemia (CLL) who achieve undetectable minimal residual disease (U-MRD) (ie, < 10(-4) 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. Materials and Methods: 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. Results: 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). Conclusions: 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. (C) 2019 Published by Elsevier Inc.