Association between statin use and survival in multiple myeloma: A systematic review and meta-analysis

Multiple myeloma (MM) remains an incurable plasma cell malignancy despite major therapeutic advances, with most patients eventually relapsing. Identifying safe, widely available adjunctive strategies that may improve survival is therefore clinically important. Statins inhibit the mevalonate pathway and downstream protein prenylation required for oncogenic Ras signaling and NF-κB activation, mechanisms implicated in myeloma proliferation and therapeutic resistance. Several population-based studies have suggested improved outcomes among statin users with MM, but the magnitude and consistency of this association remain uncertain. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review and meta-analysis of observational cohorts was performed. Adjusted hazard ratios (HRs) were pooled using a random-effects inverse- variance model. The primary outcome was all-cause mortality; the secondary outcome was MM-specific mortality. Four population-based cohorts comprising 21,129 patients were included. Statin exposure was associated with significantly improved overall survival (pooled HR 0.82, 95% confidence interval (CI) 0.76–0.89; I 2 =72.3%), corresponding to an 17% relative reduction in mortality. Two studies reporting MM-specific mortality demonstrated a consistent 25% relative reduction (HR 0.75, 95% CI 0.68–0.84; I 2 =0%). Sensitivity analyses restricted to time-varying exposure models demonstrated consistent findings, a pooled hazard ratio of 0.85 (95% CI 0.74–0.98; p = 0.023; I 2 = 84.7%), supporting robustness of the observed association with directionally concordant effects across diverse healthcare systems. Across large population-based cohorts, statin exposure was consistently associated with improved overall and disease-specific survival in MM. Given their favorable safety profile, affordability, and mechanistic relevance to myeloma biology, statins represent a promising adjunctive strategy in MM management. Prospective studies are warranted to determine whether this association reflects a true disease-modifying effect.