Real-world retrospective study of oral versus intravenous HMA-induced toxicity in MDS and AML treatment.
Authors: Palecki Julia , Bernstein Andrew , Damron Leland F. , Yi Misung , Wilde Lindsay , Keiffer Gina , Jeurkar Chetan , Kasner Margaret T. 
Published: June 2024

e18534 Background: Hypomethylating agents (HMA) are a cornerstone of therapy for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). While IV formulations have been traditionally used, the introduction of oral formulations in recent years has provided an alternative administration route. Myelosuppression is a well-documented adverse effect of HMAs, however, the differences in toxicity profiles between oral and IV forms are not yet fully described. In this retrospective study, we investigate patients who received either oral or IV HMA or both and compare the rates of cytopenias and adverse events. Methods: A cohort of 33 patients with MDS or AML treated with oral decitabine or azacitidine as active or maintenance therapy between January 1, 2016 and June 1, 2023 at Thomas Jefferson University Hospital was identified. Among these patients, 20 had also received IV hypomethylating agent (HMA) therapy. Laboratory and clinical data for treatment with oral and IV HMA therapy was collected retrospectively. The magnitude of HMA-induced cytopenias, as both absolute values and percent changes from baseline, for therapy with oral and IV HMA was calculated. For the subset of patients who received both oral and IV HMAs, the intrapatient severity of cytopenias associated with oral versus IV formulations was compared. Statistical significance was assessed utilizing paired t-tests, with a predetermined significance threshold set at p<0.05. Adverse effects for oral and IV HMA therapies are also reported. Results: In our cohort, 30 (90.9%) patients treated with oral HMA and 20 (90.9%) patients treated with IV HMA received the drug as active therapy of MDS/AML. Oral HMA treatment resulted in a mean 22% decrease in hemoglobin (Hb), 84% decrease in absolute neutrophil count (ANC), and 72% decrease in platelet count from baseline to count nadir. IV HMA treatment caused a mean 23% decrease in Hb, 92% decrease in ANC, and 83% decrease in platelet count from baseline to count nadir. No significant differences were observed in the absolute change from baseline to count nadir for Hb (p=0.69), ANC (p=0.26), or platelet count (p=0.55) between oral and IV HMA therapy. Severe adverse effects requiring hospitalization were reported in 60.6% of patients receiving oral HMA and 70% receiving IV HMA. Neutropenic fever occurred in 51.5% of patients receiving oral HMA and 60% receiving IV HMA. The most common adverse effects for both oral and IV HMA treatment included neutropenic fever, severe anemia, nausea, and fatigue. Conclusions: This retrospective study demonstrates that oral HMA induces cytopenias to a similar extent as IV HMA. Our data demonstrates comparable rates of hospitalization for adverse effects and similar incidence of neutropenic fever. Consequently, this real-world retrospective cohort study suggests that oral HMA can be considered a safe and acceptable alternative to IV HMA for patients diagnosed with MDS and AML.