PB1965: A META-ANALYSIS OF THE RATE OF MALIGNANT PROGRESSION OF MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: PRELIMINARY FINDINGS FROM A SYSTEMATIC REVIEW

Abstract

Background: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant condition preceding multiple myeloma (MM) and other haematological malignancies (HM). Clinically the rate of progression from MGUS to HM is important; current guidelines from the International Myeloma Working Group (IMWG) report this rate as “around 1% per year”, however variation has been reported by ethnic groups, MGUS type, and clinical features. Aims: A systematic review of the published literature was conducted to investigate the rate of MGUS progression to support clinical practice. Methods: Four electronic databases (Embase, Medline, Pubmed and Web of Science) were searched from database inception to 11/12/2019 using key words and MeSH subject headings for “MGUS”, “haematological malignancy” and “progression”. Studies were reviewed against predefined eligibility criteria by two independent reviewers. For studies reporting progression events and person-years of follow-up, a random-effects meta-analysis model5 was used to produce a pooled rate of MGUS progression to HM and MM. Studies reporting on cumulative rates of progression at specified time-points (1, 5 and 10-year) were included in a narrative synthesis. Results: Overall, 36 papers met the inclusion criteria; 12 studies (sample size: 114-17,963; follow-up 3.3-42.1 years) were included in the meta-analysis. In preliminary analyses, the annual pooled rate of MGUS progression was 1.1% (95%CI 0.9-1.3) to HM and 0.9% (95%CI 0.7-1.1) to MM. In total, 18 studies contributed to the narrative synthesis on MGUS progression to HM (sample size: 52-17,963; follow-up 2.1-34.1 years) and 10 studies reported on MGUS progression to MM (sample size: 75-2046, follow-up: 2.1-17 years). These narrative syntheses highlighted the heterogeneity of research, which encompassed key traits like methods, sample sizes and follow-up duration. Studies were also mainly conducted in Europe, being particularly scarce in Asia. Between meta-analysis and narrative synthesis, only seven studies reported on IgM-MGUS progression to Waldenström’s macroglobinaemia or HM, which could not be clearly synthesised in either analysis due to differing reporting; these papers indicated higher progression rates in IgM-MGUS than non-IgM. Summary/Conclusion: Preliminary findings from this systematic review support current IMWG guidelines on the rate of MGUS progression to HM. However, as the majority of studies included were limited to geographic areas within Europe and USA, further research reflecting population and clinical diversity are needed.