Cardiac safety of L-Annamycin: a pooled analysis of five clinical trials.

BACKGROUND: Anthracyclines are highly effective chemotherapeutic agents but are limited by cumulative, dose-dependent cardiotoxicity, leading to strict lifetime exposure thresholds. L-Annamycin is a next-generation liposomal anthracycline designed to preserve antitumor efficacy while reducing cardiotoxicity. METHODS: We performed a pooled analysis of cardiac safety data from five sponsor- and investigator-initiated clinical trials evaluating L-Annamycin in acute myelogenous leukemia (AML) and metastatic soft tissue sarcoma (STS). Cardiac monitoring included serial electrocardiograms, cardiac biomarkers (troponin I/T), and transthoracic echocardiography with left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) assessment. All cardiac data were independently evaluated by a cardio-oncology laboratory at the Cleveland Clinic. RESULTS: Ninety patients were included, with paired echocardiographic data available in 78. Median cumulative L-Annamycin dose was 660 mg/m2 (IQR 450-1,080). Baseline and post-treatment LVEF did not differ significantly (60.6% vs. 60%, p = 0.84). No associations were observed between change in LVEF and cumulative dose or age. Serial ECG, troponin, and GLS assessments showed no treatment-related cardiotoxicity. These findings were observed despite cumulative exposures exceeding conventional anthracycline lifetime limits. CONCLUSIONS: In this pooled analysis of patients with AML and STS, L-Annamycin was not associated with clinical or subclinical evidence of cardiotoxicity at cumulative doses exceeding traditional anthracycline thresholds. These data support continued clinical evaluation of L-Annamycin as a potentially safer anthracycline platform.