Oral Azacitidine Maintenance After CPX ‐351 in Transplant‐Ineligible Patients With Therapy‐Related or Myelodysplasia‐Related Acute Myeloid Leukemia

To the Editor, CPX-351 has become a standard intensive induction regimen for older patients with therapy-related acute myeloid leukemia (t-AML) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) [1,2].Although allogeneic hematopoietic cell transplantation (allo-HCT) remains the preferred consolidation strategy for eligible patients in first remission, a substantial proportion of older or unfit patients are not candidates for transplantation [3].To note, median overall survival (OS) for patients not transplanted after CPX-351 in the pivotal study was only 14 months [4].For these patients, the optimal post-remission strategy remains an unmet clinical need.Oral azacitidine (oral AZA; CC-486) prolongs OS in transplant-ineligible patients with AML in first remission, based on the QUAZAR AML-001 trial [5].However, patients with secondary AML were underrepresented in that study, and all patients had received conventional 7 + 3 chemotherapy.Thus, whether oral AZA provides benefit following CPX-351 remains uncertain.We conducted an international, real-world, retrospective, multicenter study evaluating oral AZA maintenance in adults with t-AML or myelodysplasia-related acute myeloid leukemia (AML-MR) who achieved first remission after CPX-351 and were not eligible for allo-HCT.Patients were identified across 13 centers in France, United States, Italy, Germany, and Australia between January 2020 and July 2024.Eligible patients had newly diagnosed t-AML or AML-MR; had not previously received a hypomethylating agent; achieved a first complete remission (CR1, CRh1, or CRi1) following CPX-351; were not eligible for allo-HCT and subsequently received oral AZA maintenance.Oral AZA was administered at the approved dose of 300 mg once daily for 14 days of a 28-day cycle.For comparison, we assembled a hybrid control cohort of 112 non-transplanted patients with t-AML or AML-MR who achieved CR(i)1 after CPX-351 but did not receive maintenance therapy or allo-HCT.