High-dose regimens of hypomethylating agents promote transfusion independence in IPSS lower-risk myelodysplastic syndromes: a meta-analysis of prospective studies

The hypomethylating agents (HMAs) azacytidine (AZA) and decitabine (DAC) are usually administered after the failure of erythropoietin-stimulating agents for lower-risk myelodysplastic syndromes (LR-MDS). However, it is unclear whether one of these HMAs has superior efficacy and safety. This was investigated in the present study by means of a meta-analysis of prospective studies published between January 1990 and July 2020 in PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov databases; 19 studies with 1076 patients were included in the final analysis. The transfusion independence (TI) rate (66.7% [95% confidence interval: 41.7%–87.4%]) was higher with AZA 75 mg/m(2)/day for 7 days than with other regimens (all p<0.025). The proportion of patients with intermediate-1 risk influenced overall survival (p<0.05). There were no differences in treatment response, survival, and adverse event rates between patients treated with AZA (75 mg/m(2)/day for 5 days) and DAC (20 mg/m(2)/day for 3 days), although the latter group had a higher rate of grade 3/4 anemia (15.8% vs 0.0%; p<0.0001) and lower rate of diarrhea/constipation (6.9% vs 25.0%; p=0.002). Thus, both HMAs at high doses achieved reasonable response and TI rates with acceptable side effects, but did not prolong the overall survival in LR-MDS patients.