Oral Versus Intravenous Hypomethylating Agents in Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Multicenter Real-World Toxicity Comparison.

BACKGROUND

Hypomethylating agents (HMAs) are a cornerstone of therapy for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Oral formulations offer an alternative to intravenous (IV) administration, but comparative real-world toxicity data remain limited. We evaluated hematologic toxicity and adverse events associated with oral versus IV HMAs.

METHODS

We conducted a multicenter retrospective cohort study of 33 patients with MDS or AML treated with oral decitabine/cedazuridine or oral azacitidine between January 1, 2016 and June 1, 2023 across three academic cancer centers. Twenty patients who also received IV HMAs were included in an intrapatient paired analysis. Cytopenias were assessed by absolute values and percent change from baseline to nadir. Wilcoxon signed-rank tests were used for intrapatient comparisons, and clinically significant adverse events were recorded descriptively.

RESULTS

Among the 20 patients included in the intrapatient analysis, median decreases in hemoglobin were 20.8% during oral HMA therapy and 20.5% during IV HMA therapy. Median decreases in absolute neutrophil count were 95.9% and 97.3%, respectively, while median decreases in platelet count were 81.9% and 88.6%, respectively. No statistically significant differences were observed between oral and IV HMA therapy for hemoglobin (p = 0.60), absolute neutrophil count (p = 0.63), or platelet count (p = 0.06). Hospitalization occurred in 60.6% of patients during oral HMA therapy and 70.0% during IV HMA therapy, while neutropenic fever occurred in 51.5% and 60.0%, respectively.

CONCLUSIONS

Oral HMAs demonstrated cytopenia severity and adverse event rates comparable to IV HMAs, supporting oral formulations as a practical alternative in patients with MDS and AML. Although encouraging, these findings should be interpreted in the context of the retrospective design and modest sample size.