Introduction Liposomal daunorubicin/cytarabine (CPX-351) is approved for treating patients with therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes (AML-MRC). This study aimed to evaluate clinical outcomes in patients who received CPX-351 at our institution over the past decade.

Methods We retrospectively reviewed adult AML patients (≥18 years) diagnosed and treated at the University of Kentucky Markey Cancer Center between January 2015 and June 2025. Patients who received CPX-351 for induction were included. Demographics, cytogenetic and molecular profiles, and treatment details were abstracted from medical records. AML was diagnosed per 2016 WHO criteria. Molecular testing was performed using a validated CLIA-certified 97-gene NGS panel with a 5% variant allele frequency threshold. Treatment response was assessed using ELN 2022 criteria. Primary endpoints included composite complete remission (CR) or CR with incomplete hematologic recovery (CRi), relapse rates, relapse-free survival (RFS), and overall survival (OS). RFS and OS were estimated using Kaplan-Meier analysis, censoring at the time of allogeneic stem cell transplantation. Logistic regression identified predictors of CR/CRi and relapse, and Cox proportional hazards modeling was used for survival outcomes. Statistical significance was defined as p<0.05. Analyses were performed using R version 4.4.1.

Results Forty patients received CPX-351 as primary induction. The median age was 62 years (range 33–73), with equal distribution of males and females (n=20 each). Seventeen patients (43%) had antecedent MDS, and ten (25%) had therapy-related AML; the remainder had morphologic (13%), cytogenetic (18%), or molecular features (13%) consistent with AML-MRC.

Fourteen patients (35%) had a normal karyotype, ten (25%) had a complex karyotype, nine (23%) had isolated -7/del(7q), and three (8%) had isolated abnormal 17p. At least one molecular mutation was present in 90% of patients, most frequently DNMT3A (30%), RUNX1 (25%), SRSF2 (25%), TP53 (20%), ASXL1 (20%), FLT3 (18%; 10% FLT3-ITD), TET2 (18%), NPM1 (15%), NRAS (15%), PTPN11 (13%), IDH2 (13%), GATA (10%), and BCOR (10%).

Nineteen patients (48%) achieved CR/CRi, including one who required two cycles of induction. Ten patients (25%) achieved partial remission. Thirteen patients received CPX-351 consolidation, with a median of two cycles (range 1–4). Fourteen patients ultimately proceeded to allogeneic stem cell transplantation. Among CR/CRi responders, 12 (63%) relapsed during a median follow-up of 9.2 months. Median RFS was 5.1 months (95% CI, 3.8–12.1). Median OS for the entire cohort was 9.2 months (95% CI, 6.6–14.3), and 11 patients were alive at the time of analysis.

On logistic regression, del(7q) was identified as a negative predictor of CR/CRi (OR for CR/CRi 0.20; 95% CI, 0.04–0.75). No demographic or genetic factor significantly predicted relapse or RFS. Achieving CR/CRi was the only predictor variable that was significantly associated with OS (HR for death 0.43, 95% CI 0.19 - 0.97).

Conclusion In this single-center cohort, CPX-351 demonstrated modest remission rates in patients with AML-MRC and therapy-related AML, with over half of responders experiencing relapse within a year. Outcomes were poorest in patients with del(7q). These findings underscore the need for additional strategies to improve long-term disease control in this high-risk population.

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2025
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