Adverse Events in 1406 Patients Receiving 13,780 Cycles of Azacitidine within the Austrian Registry of Hypomethylating Agents—A Prospective Cohort Study of the AGMT Study-Group

SIMPLE SUMMARY: Azacitidine is thus far the only drug shown to prolong overall survival and is, therefore, the recommended (backbone) treatment in patients diagnosed with myelodysplastic syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia who are not eligible for intensive chemotherapy. Detailed reports on adverse events are often lacking. We performed a thorough analysis of the adverse events that occur during treatment with azacitidine in the largest cohort of patients treated with this drug published so far. We also compared the frequency of adverse events documented in our cohort to published data from randomized clinical trials with an azacitidine monotherapy arm. Adverse event documentation in the Austrian Registry was high. Hematologic adverse events occurred at a similar rate compared to published trials, whereas gastrointestinal toxicities were significantly less commonly reported. Our data complement results from clinical trials with real-world evidence and form a reference for future combination strategies with azacitidine. ABSTRACT: Background: Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. Detailed reports on adverse events in a real-world setting are lacking. Aims: To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents. To compare real-world data with that of published randomized clinical trials. Results: A total of 1406 patients uniformly treated with a total of 13,780 cycles of azacitidine were analyzed. Hematologic adverse events were the most common adverse events (grade 3–4 anemia 43.4%, grade 3–4 thrombopenia 36.8%, grade 3–4 neutropenia 36.1%). Grade 3–4 anemia was significantly more common in the Registry compared to published trials. Febrile neutropenia occurred in 33.4% of patients and was also more common in the Registry than in published reports. Other commonly reported adverse events included fatigue (33.4%), pain (29.2%), pyrexia (23.5%), and injection site reactions (23.2%). Treatment termination due to an adverse event was rare (5.1%). Conclusion: The safety profile of azacitidine in clinical trials is reproducible in a real-world setting. With the use of prophylactic and concomitant medications, adverse events can be mitigated and azacitidine can be safely administered to almost all patients with few treatment discontinuations.