Maintenance Azacitidine in Acute Myeloid Leukemia

Primary Indication and Contraindications

The European Society for Medical Oncology (ESMO) guidelines state that maintenance azacitidine should not replace allogeneic HSCT in transplant-eligible candidates, as it is specifically for patients who are not immediate candidates for HSCT, have achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after intensive chemotherapy, and are ≥55 years of age 4, 1
The ESMO guidelines explicitly state that maintenance with hypomethylating agents after allogeneic HSCT cannot be recommended outside clinical trials, as it is Level V, Grade D evidence 4, 1, 2

The rationale against routine post-HSCT HMA maintenance includes unclear whether prophylactic HMA treatment prevents relapse, may increase toxicity without therapeutic benefit in patients curable with HSCT alone, and phase I/II data showed 21% 1-year relapse rate but lacks randomized controlled evidence 4, 1, 2
Pre-emptive treatment when mixed chimerism or minimal residual disease (MRD) appears may be more rational than prophylactic maintenance post-HSCT 4, 1, 2

Azacitidine (with or without venetoclax) serves as first-choice therapy for newly diagnosed AML patients ineligible for intensive chemotherapy, not as maintenance in this population, according to the ESMO guidelines 4, 1, 3

Do not use subcutaneous azacitidine maintenance based solely on disease-free survival benefit when oral formulation shows overall survival advantage, as stated by the ESMO guidelines 1
Do not delay or replace allogeneic HSCT with azacitidine maintenance in transplant-eligible patients, as recommended by the ESMO guidelines 4, 1
Do not routinely use HMA maintenance post-HSCT outside clinical trials despite phase I/II data, according to the ESMO guidelines 4, 1, 2
Do not confuse first-line azacitidine therapy in unfit patients with maintenance therapy in fit patients achieving remission, as clarified by the ESMO guidelines 4, 3