DP091 | EFFICACY OF CPX-351 IN SECONDARY ACUTE MYELOID LEUKEMIA DEFINED ACCORDING TO WHO 2022 CLASSIFICATION.

Background and Aims: Recent insights into AML ontogeny are shifting the definition of secondary AML (s-AML) from clinical to molecular, as reflected in the 2022 WHO classification. It prioritizes 1) MDS-related gene mutations, 2) cytogenetic aberrations, and 3) clinical history of MDS, defining three s-AML categories. CPX-351 is more effective than 3+7 for s-AML and is approved per WHO 2016, which did not include molecular criteria. Data on CPX-351 efficacy in molecularly defined s-AML is limited. This study compares outcomes of elderly s-AML patients treated with CPX-351 using both WHO 2016 and 2022 classifications to assess its efficacy in molecular s-AML. Methods: NGS was performed at diagnosis using the SOPHiA Genetics Myeloid Solution panel (34 genes), on Illumina MiSeq. Data analysis used SOPHiA DDM®. AML with MDS-related mutations was defined per WHO 2022. MRD was assessed by multicolour flow cytometry (threshold 0.1%) in all CR patients. Results: Eighty-five patients (median age 69) with WHO 2016-defined s-AML treated with CPX-351 were included. Per WHO 2016, 21 (25%) had t-AML, 55 (64%) s-AML with MDS cytogenetics, and 9 (11%) morphologically defined s-AML. WHO 2022 reclassified 69 (82%) as s-AML with genetic aberrations, 13 (15%) with cytogenetic changes, and 3 (3%) by MDS history only. CR was achieved in 66 patients (78%) with 3 early deaths (3.8%). MRD negativity occurred in 48 (72%) of CR patients. CR rate and MRD negativity were unaffected by WHO 2016/2022 classification or ELN risk. After 42.1 months’ median follow-up, median OS was 19 months; 2-year OS was 40.2%. By WHO 2022, median OS was 21 months with MDS-related gene mutations and 18 without (p<0.05, Figure 1). Twenty-three patients received HSCT in first CR; median OS was not reached. HSCT was the only factor independently linked to longer OS (p<0.05). HSCT outcomes were not influenced by presence of MDS mutations (p=n.s.). Conclusion: CPX-351 shows high efficacy in s-AML, including molecularly defined cases per WHO 2022. Patients with MDS-related gene mutations had similar outcomes to others, supporting the drug’s use across s-AML subtypes.