CPX-351 vs. conventional chemotherapy cardiotoxicity in high-risk AML: a post hoc phase III trial analysis

Background: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has demonstrated significantly improved overall survival in acute myeloid leukemia (AML) compared with 7 + 3, but its impact on cardiac function remains unclear. In a post hoc analysis of the pivotal clinical trial, we sought to determine the relative cardiotoxicity of CPX-351 vs. 7 + 3 in high-risk AML. Methods: We evaluated cardiotoxicity in 102 patients with AML (CPX-351, n = 57; 7 + 3, n = 45) who had normal baseline left ventricular ejection fraction (LVEF) ≥ 53% and at least one post-baseline echocardiographic assessment. Cardiotoxicity was assessed through reported cardiac adverse events (AEs) and core lab assessment of echocardiograph changes in LVEF and/or left ventricular global longitudinal strain (GLS). Results: A clinically significant change in LVEF (absolute change from baseline > 10% and LVEF <53%) and GLS (relative change from baseline > 12% and GLS < 18%) was less common with CPX-351 vs. 7 + 3 at follow-up 1 and/or 2 (8.8% vs. 20.0% and 21.1% vs. 44.4%, respectively). No CPX‑351-treated patients evaluated at final follow-up (follow-up 2) had decreased LVEF < 53% at follow-up 2, compared to 17.8% of 7 + 3-treated patients. The frequency of reported cardiac AEs was similar with CPX-351 (40.4%) and 7 + 3 (42.2%); most frequent were tachycardia in CPX-351-treated patients (CPX-351, 21.1%; 7 + 3, 8.9%) and atrial fibrillation/flutter in 7 + 3-treated patients (CPX-351, 7.0%; 7 + 3, 11.1%). Conclusion: In addition to improving overall survival as demonstrated in the pivotal trial, CPX-351 may also be associated with less cardiotoxicity than 7 + 3 in high-risk AML patients.