SARS-CoV-2 infection, vaccination, and MGUS progression with COVID-19 outcomes in multiple myeloma: A systematic review.

Abstract

e19550 Background: SARS-CoV-2 infection and vaccination have been associated with immune perturbations that may affect plasma cell biology. Whether these exposures influence progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) through immune dysregulation or clonal selection remains uncertain, and patients with MM continue to demonstrate vulnerability to adverse COVID-19 outcomes. Methods: A systematic review with selective quantitative synthesis of observational studies in accordance with PRISMA guidelines. A PubMed search was conducted through December 2024. Eligible studies included adult populations with MGUS or MM reporting outcomes following SARS-CoV-2 infection or vaccination; case reports, narrative reviews, and studies without extractable data were excluded. Data sources included population-based longitudinal cohorts, multicenter registries, and real-world datasets. Outcomes included longitudinal biomarkers of MGUS progression, COVID-19–associated mortality in MM, and vaccine-era breakthrough infection and hospitalization. Risk of bias was assessed using ROBINS-I. MGUS outcomes were synthesized narratively; random-effects meta-analysis was performed for comparable mortality outcomes. Vaccine-era outcomes were summarized using hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Eleven studies met inclusion criteria, with five eligible for quantitative synthesis. In population-based iStopMM cohorts, longitudinal mixed-effects models showed no association between SARS-CoV-2 infection (Exp[β]=1.01, 95% CI 0.91–1.12) or vaccination (Exp[β]=0.99, 95% CI 0.96–1.03) and change in M-protein trajectory, indicating stable MGUS clonal kinetics. In contrast, among MM cohorts during the early pandemic, COVID-19–associated mortality ranged from 24% in a New York City cohort to 34% in an international registry. Despite vaccination, MM remained associated with increased risk of breakthrough SARS-CoV-2 infection versus matched controls (HR 1.34, 95% CI 1.06–1.69) and markedly increased risk of hospitalization after breakthrough infection (HR 15.9, 95% CI 6.2–40.3), consistent with persistent immune dysfunction. Conclusions: Across population-based longitudinal cohorts, SARS-CoV-2 infection and vaccination were not associated with altered MGUS clonal dynamics or accelerated progression, providing reassurance regarding stability of premalignant plasma cell disorders. Intensified surveillance solely due to prior SARS-CoV-2 infection or vaccination is unlikely to be warranted in MGUS. In contrast, patients with MM continue to experience substantial COVID-19–related morbidity in the vaccine era, supporting ongoing prioritization of preventive and early therapeutic strategies.