Dose schedule modifications of 5-azacitidine monotherapy in myelodysplastic neoplasias and chronic myelomonocytic leukaemia.
Key claim: Alternative 5-azacitidine schedules (5-0-0 and 5-2-2, and limited 100 mg/m² ×5-day data) appear non-inferior to the standard 75 mg/m² 7-day regimen for overall survival, response, transfusion independence, and toxicity in high-risk MDS and CMML.
Abstract
5-azacitidine (5-AZA) is the first hypomethylating agent synthetized and the cornerstone treatment for high-risk myelodysplastic neoplasms (MDS) and chronic myelomonocytic leukaemia (CMML). Although the validated schedule is 75 mg/mfor 7 days (7-0-0), alternative schedules have been studied in terms of efficacy, complications and survival. The 7-0-0 shows an overall survival (OS) between 21 and 25 months in prospective and 16.5-27 months in retrospective studies and complete response (CR) rates between 7% and 18%. Alternative schedules, mostly 5-day (5-0-0) or 7-day with weekend pause (5-2-2) at 75 mg/m, perform equally in terms of OS and CR with the 7-0-0, with a slight superiority for the 5-2-2, although direct comparisons are rare and almost always non-significant. Similarly, transfusion independence, time to leukaemia transformation and toxicities did not differ significantly across studies. For more intensive schedules, using 100 mg/mfor 5 days, literature is limited, but response rates, survival and safety seem to be comparable to the 75 mg/mdose. In CMML, 5-AZA monotherapy yields satisfying overall response rates of 40% or more, with myelodysplastic subtype responding better than myeloproliferative. In all, alternative 5-AZA schedules seem non-inferior in terms of efficacy and toxicities and can be used as an alternative according to local protocols and patient choice.
Why this matters
Alternative 5-azacitidine schedules (5-0-0 and 5-2-2, and limited 100 mg/m² ×5-day data) appear non-inferior to the standard 75 mg/m² 7-day regimen for overall survival, response, transfusion independence, and toxicity in high-risk MDS and CMML.