Translational Research on Azacitidine Post- Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2)

Achieving complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undergoing curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong leukemia-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) versus best supportive care (BSC) in elderly AML patients who achieved CR after intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next Generation Sequencing (NGS). We analyzed baseline, randomization, and 6-month post-remission samples from 24 patients (median age 71, 12 males). High-throughput NGS targeted 350 myeloid malignancy-related genes, considering variants with a Variant Allele Frequency (VAF) ≥ 4%. At diagnosis, all patients had 5 to 17 (median 10) mutations, with DNMT3A (42%), NPM1 (33%), and TET2 (33%) being most frequent. FANCA mutations in 4 patients were linked to a higher relapse risk (HR 4.96, p=0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications.