Intermediate doses cytarabine after induction with CPX-351 for patients with secondary AML: safety and efficacy

Acute myeloid leukemia (AML), especially therapy-related (t-AML) or secondary AML (s-AML), presents complex therapeutic challenges. CPX-351, a liposomal formulation of cytarabine and daunorubicin, has demonstrated superior outcomes compared to standard 7 + 3 chemotherapy. However, optimal post-remission strategies are debated. This retrospective study evaluates the feasibility and efficacy of intermediate-dose ARA-C (IDAC), total dose of 8-9 g/m(2), following CPX-351 in 47 patients from three Italian centers. Median patient age was 69, with 64% having AML with myelodysplasia-related changes (MRC-AML). Based on the 2017 European LeukemiaNet (ELN) risk stratification, 8 patients were classified as favorable, 20 as intermediate, and 19 as adverse. The median overall survival (OS) was 21 months (IC95% 17-43), with 85% alive at 12 months and 48.4% at 24 months. Event-free survival (EFS) was 14.9 months (IC95% 11.7-28.2). Multivariate analyses identified adverse-risk ELN-2017 and MRD-positivity after CPX-351 as negative predictors for OS. IDAC was well tolerated, with manageable toxicities: neutropenic fever (27, grade 1-3) and mucositis (4, grade 2-3). Importantly, 70% of patients achieved stable or improved measurable residual disease (MRD) after consolidation. The study underscores IDAC as a viable consolidation strategy, especially for patients unable to receive further CPX-351 or awaiting transplant. Despite its retrospective nature and limited sample size, the findings suggest that IDAC may offer improved outcomes, including lower costs, compared to CPX-351.