Rate of MGUS progression to haematological malignancies: a systematic review

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic pre-cancerous condition that precedes plasma cell dyscrasias, including multiple myeloma (MM). Current clinical guidelines report that MGUS's rate of malignant progression to haematological 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 March 2024 for articles reporting these outcomes; articles were summarised using meta-analysis and narrative synthesis. Findings were incorporated from n = 46 studies, published between 1991 and 2024 and conducted across n = 17 countries. Median follow-up ranged from 1.3 to 34.2 years and sample sizes ranged from n = 63 to 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 1000 person-years to HM, equivalent to 1.2% per year (95% CI: 1.0%–1.5%) and 8 per 1000 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. 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.