Rate of MGUS progression to haematological malignancies: a systematic review

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic pre-cancerous condition which precedes plasma cell dyscrasias, including multiple myeloma (MM). Current clinical guidelines report that MGUS’s rate of malignant progression to hematological malignancy (HM) is ~1% per year, however reported rates have varied widely. To address this discrepancy, a systematic review was conducted, investigating MGUS’s rate of malignant progression to HM, and MM alone. Four electronic databases were searched from inception to 28/3/24 for articles reporting these outcomes; articles were summarised using meta-analysis and narrative synthesis. <br/>Findings were incorporated from n=46 studies, published between 1991-2024 and conducted across n=17 countries. Median follow-up ranged from 1.3-34.2 years and sample sizes ranged from n=63-17,963. In random-effects meta-analysis, n=13 studies reported on MGUS progression to HM and n=12 reported on progression to MM. The overall estimates of malignant progression events were 12 per 1,000 person-years to HM, equivalent to 1.2% per year (95%CI: 1.0-1.5%) and 8 per 1,000 person-years to MM, or 0.8% per year (95%CI: 0.7-1.1), with substantial heterogeneity between studies (I²: 96.7% and 95.8%, respectively). Progression rates varied widely in narrative synthesis; at 10 years, studies reported annual MGUS progression rates of 6.6-33.6% to HM and 7.0-28.5% to MM. <br/>While progression rates aligned with clinical guidelines overall, studies’ varied findings present opportunities for further research, exploring the impact of world region, follow-up duration and study methods. Considering this, caution should be taken when informing clinicians and patients about the risk of progression from MGUS to MM.