Background: Despite expanding therapeutic armamentarium of multiple myeloma (MM), it remains an incurable disease. Therefore, there is a need to assess the impact of deeper hematological responses to better gauge treatments in clinical trials and routine practice. The presence of minimal residual disease (MRD), is becoming crucial and a new standard in monitoring remission status. Clinical evidence shows that MRD status after treatment is an independent prognostic factor for MM. This review summarizes current data on MRD status and its role in predicting progression-free survival (PFS) and overall survival (OS) outcomes. Methods: We performed a literature search on four databases (PubMed, Embase, Cochrane, and Web of Science) following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. We screened 1307 studies using the Mesh terms “Multiple Myeloma and Minimal Residual disease.” After excluding review, duplicate, and non-relevant articles, 7 studies were included. Results: The association between MRD status and outcomes, including survival in TIE-NDMM patients was assessed in 7 studies, including 1083 patients. MRD status was determined using different techniques, such as flow cytometry and clonoSEQ. Different regimens were used in all studies. PFS was reported in all studies. Compared with MRD positive status, achieving MRD negativity improved PFS to 58 months versus 28.65 months as per cumulative analysis. The cumulative OS reported in 2 studies (n=196) was 95.85% in MRD-negative patients compared to 55.65% in MRD positive patients. Conclusions: Further clinical data focusing on post-treatment assessment of MRD will be useful in clinical decision-making and could be practice changing. MRD status may serve as surrogate end-points for PFS and OS in ongoing and future clinical trials. Achieving durable MRD negativity with PFS improvement might also increase the time between treatment relapses for MM and might help switch to a lesser aggressive regimen, chemotherapy-free period, avoiding drug toxicity.

NR: Not reached, NA=Not available, PFS: Progression free survival, OS: Overall survival, MRD: Minimal residual disease