Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis.
Munshi NC., Avet-Loiseau H., Rawstron AC., Owen RG., Child JA., Thakurta A., Sherrington P., Samur MK., Georgieva A., Anderson KC., Gregory WM.
IMPORTANCE: Numerous studies have evaluated the prognostic value of minimal residual disease (MRD) in patients with multiple myeloma (MM). Most studies were small and varied in terms of patient population, treatment, and MRD assessment methods. OBJECTIVE: To evaluate the utility of MRD detection in patients with newly diagnosed MM. DATA SOURCES: A Medline search was conducted for articles published in English between January 1990 and January 2016. STUDY SELECTION: Eligible studies reported MRD status and progression-free survival (PFS) or overall survival (OS) in 20 or more patients following treatment. Among 405 articles identified, 21 met the initial eligibility criteria and were included in the analysis. DATA EXTRACTION AND SYNTHESIS: Information on patient characteristics, treatment, MRD assessment, and outcomes were extracted using a standard form. MAIN OUTCOMES AND MEASURES: The impact of MRD status on PFS and OS was assessed by pooling data from relevant trials. Data were adjusted to allow for different proportions of patients with MRD in different studies, and analyzed using the Peto method. Forest plots were created based on Cox model analysis. Other prespecified research questions were addressed qualitatively. RESULTS: Fourteen studies (n = 1273) provided data on the impact of MRD on PFS, and 12 studies (n = 1100) on OS. Results were reported specifically in patients who had achieved conventional complete response (CR) in 5 studies for PFS (n = 574) and 6 studies for OS (n = 616). An MRD-negative status was associated with significantly better PFS overall (hazard ratio [HR], 0.41; 95% CI, 0.36-0.48; P