Publication Date:
2019-11-13
Description:
Introduction: Achievement of MRD negativity in MM is associated with prolonged progression-free survival (PFS) and is being investigated as a potential surrogate for established clinical endpoints, such as PFS and overall survival (OS). Here, we evaluated the predictive utility of MRD in patients (pts) with MM for PFS and OS using a systematic literature review (SLR) and meta-analysis, and investigated how hazard ratios (HR) for PFS and OS, stratified by MRD status, changed for various pt subgroups. Methods: A SLR was conducted to identify all studies in MM reporting survival outcomes by MRD status (through 8 June 2019). In these studies, MRD was assessed by various assays (multiparametric flow cytometry [MFC], next generation sequencing [NGS], and polymerase chain reaction [PCR]), sensitivity thresholds (10-4, 10-5, and 10-6), and disease settings (relapsed/refractory MM [RRMM], transplant-eligible [TE] and transplant-ineligible [TIE] newly diagnosed MM [NDMM]). Studies with allogeneic transplant, where MRD was measured in peripheral blood or using PET-CT, or from which PFS and OS data could not be extracted were excluded from the analysis. To obtain a pooled effect estimate of MRD status on PFS and OS HRs, a meta-analysis was performed. Subgroup analyses were performed to adjust for variables expected to impact the association of MRD and PFS/OS outcomes. Variables were selected based on available qualitative evidence from studies. Statistical analyses were performed using the 'metafor' R package for meta-analyses. Results: 143 publications met the inclusion criteria; 86 publications were included in the meta-analysis based on data availability (65 PFS and 28 OS HRs). Outcomes for PFS (N = 8590) and OS (N = 3392) were significantly improved for MRD-negative pts: PFS HR 0.35 (95% confidence interval [CI], 0.31-0.39) and OS HR 0.48 (95% CI, 0.41-0.55; P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine