Iron Chelation Therapy in Low- to Intermediate- Risk Myelodysplastic Syndrome Patients: A Systematic Review and Meta-Analysis

Background Transfused patients with low- to intermediate-risk myelodysplastic syndromes (MDS) are known to suffer from iron overload. Iron chelation therapy (ICT) may improve outcomes, however, it remains to be thoroughly investigated. Methods We conducted a systematic review and meta-analysis to assess the benefit of ICT in patients with MDS. MEDLINE, EMBASE, and Cochrane CENTRAL were searched for studies on ICT for low- to intermediate-risk MDS that reported adjusted hazard ratios (aHR) or overall survival (OS). Two reviewers independently screened titles and abstracts and subsequent full texts for eligibility. Studies were extracted for general demographics, AML progression rate, incidence of cardiac injury, and median OS or aHR. aHR risk ratios were calculated using a random-effects model meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and Newcastle-Ottawa scale for non-randomized studies. Results The initial search yielded 1177 citations, of which we included 11 observational studies (n = total patient number) and one RCT (n = total patient number) for analysis. The heterogeneity was moderate (I 2=57%; P=0.02). There was a significant reduction in risk of mortality in patients with iron overload and low- or intermediate-risk MDS treated with ICT (aHR 0.43; 95% CI 0.32-0.57; P < 0.00001) (figure 1). The median OS among patients receiving ICT and patients receiving no ICT was reported for nine studies. The median OS for patients receiving ICT was consistently longer than the median OS in the non-ICT group across all studies (figure 2). Conclusion Iron chelation therapy (ICT) is associated with a lower risk of mortality in low- to intermediate- risk myelodysplastic syndrome patients. Given the limited number of RCTs, more high-quality studies are required before ICT becomes a standard of care for this group of patients [Display omitted] Crowther: Syneos Health: Honoraria; Precision Biologicals: Honoraria; Pfizer: Speakers Bureau; CSL Behring: Speakers Bureau; Bayer: Speakers Bureau; Hemostasis reference laboratories: Honoraria.