BACKGROUND: Azacitidine and Decitabine are widely used agents in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), especially in patients who are unfit for intensive treatment. Despite increased usage, the comparative evidence regarding outcomes has been limited and inconsistent. It is essential to understand the difference between efficacy of these agents and their side effect profile to make an informed decision for improving patient outcomes.

AIMS: The objective of this systematic review and meta-analysis was to evaluate for comparative efficacy and side effects profile of azacitidine and decitabine in AML and MDS.

METHODS: A comprehensive literature search was conducted on PubMed, ClinicalTrials.gov, and Cochrane was conducted in April 2025 according to the PRISMA guidelines. Of 103 articles, 12 original studies reporting outcomes AML/MDS treated with azacitidine and decitabine were included. The data on demographics, response rates, and adverse events was extracted. The pooled estimates were analyzed using random effects model in MetaXL package for Microsoft Excel. Results were expressed as prevalence estimates with 95% confidence intervals (CIs). Heterogeneity across studies was evaluated using the I² statistic, and sensitivity was checked to assess the influence of individual studies.

RESULTS: A total of 1,256 patients were included in the analysis: 434 with acute myeloid leukemia (AML) and 822 with myelodysplastic syndromes (MDS). Among them, 868 patients (AML: 181; MDS:687) received azacitidine while 388 (AML: 253; MDS: 135) received decitabine.

In the azacitidine arm, among 689 patients with reported gender, 416 were males (60.37 %) and the median age was 69.9 years (28-91). The median follow-up was 13.7 months (0.3-76.4), with a mean overall survival of 12.5 months (0.8-89.3). The pooled response rates were: overall response rate (ORR) 58% (95% CI: 0.52-0.64), complete response (CR) 36% (95% CI: 0.30-0.42), partial response (PR) 2% (95% CI: 0.00-0.06), stable disease (SD) 18% (95% CI: 0.12-0.25), and progressive disease (PD) 6% (95% CI: 0.02-0.12). The pooled incidence rates across the studies were 31.4% for febrile neutropenia (95% CI: 18.3-44.5, p < 0.0001), 42.3 % for thrombocytopenia (95% CI: 29.6-54.9, p < 0.0001), and 35.71% for leukopenia (95% CI: 23.99-35.71, p < 0.001).

In the decitabine arm, 252 patients were males (64.94%, n=252) and the median age was 71 (21-92.3). The median follow-up was 33.1 months (1-55.1) with the mean overall survival of 11.65 months (5.8-14). The pooled response rates were: ORR 73% (95% CI: 0.48-0.93) and CR 63% (95% CI: 0.05-0.98). The pooled incidence rates across studies were 82.7% for neutropenic fever (95% CI: 13.5-89.1, p=0.0034), 10.2% for sepsis (95% CI: -1.8-22.2, p < 0.001), and 18.3% for lung infection (95% CI: 8.3-35.7, p < 0.01).

CONCLUSION: In AML/MDS, both azacitidine and decitabine demonstrate activity. Decitabine achieved higher overall and complete response rates but was associated with serious infections and hematologic adverse events. Azacitidine showed modest effectiveness but better tolerability. More head to head studies are required for defining superior HMAs with tolerable adverse events.

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2025
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