L-Annamycin was not associated with significant changes in LVEF from baseline (mean difference, -0.12%; 95% CI, -1.34 to 1.09; p=0.84) despite high cumulative anthracycline exposure.
Does L-Annamycin cause cardiotoxicity (measured by LVEF change) in patients with AML and soft tissue sarcoma?
L-Annamycin demonstrated no detectable cardiotoxicity or significant change in LVEF despite high cumulative anthracycline exposure in patients with AML and soft tissue sarcoma.
Estimación del efecto: mean difference -0.12% (95% CI -1.34 to 1.09)
valor p: p=0.84
12025 Background: Anthracyclines are widely used chemotherapeutic agents but limited by dose-dependent cardiotoxicity and lifetime cumulative dose restrictions. L-Annamycin is a next-generation anthracycline designed to eliminate cardiotoxicity and overcome multidrug resistance. In a Phase 1b/2 study in patients with acute myeloid leukemia (AML), L-Annamycin administered in combination with cytarabine as second-line therapy achieved a 50% complete remission (CR) rate and a 60% composite CR (CRc) rate with a median overall survival of 12.39 months (95% CI, 2.07–13.96) in the intent-to-treat population. We evaluated the cardiac safety of L-Annamycin in multiple clinical trials to assess its ability to support sustained anthracycline exposure in patients with AML and soft tissue sarcoma. Methods: Cardiac safety was evaluated across sponsor- and investigator-initiated clinical trials of L-Annamycin. Assessments included serial 12-lead electrocardiograms (ECGs), cardiac biomarkers (troponin I and T), and transthoracic echocardiography with centralized evaluation of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), where available. Cardiac data were reviewed independently by a reviewer in the Division of Cardiovascular Medicine at the Cleveland Clinic. Changes in LVEF from baseline to final assessment were analyzed in relation to cumulative L-Annamycin dose and patient age. Results: An independent cardiac safety review was conducted for 90 patients who were treated with L-Annamycin across five completed clinical trials; 78 of these patients now have source-verified pre- and post-treatment left ventricular ejection fraction (LVEF) assessments. The median cumulative L-Annamycin dose among these patients was 660 mg/m² (95% CI, 645–690; range, 210–2,970 mg/m²), with most of the cumulative doses exceeding conventional lifetime anthracycline limits. Analysis of the change in LVEF from baseline to final assessment demonstrated no statistically significant difference (mean difference, −0.12%; 95% CI, −1.34 to 1.09; p = 0.84). Linear regression analysis documented no correlation between cumulative L-Annamycin dose and change in LVEF (p = 0.12), nor between patient age and change in LVEF (p = 0.73). Independent review of serial ECGs, cardiac biomarkers, cardiac adverse events, and available global longitudinal strain measurements also demonstrated no evidence of drug-induced cardiotoxicity. Conclusions: L-Annamycin was not associated with any detectable cardiotoxicity despite high cumulative anthracycline exposure. These findings suggest that L-Annamycin represents a next-generation anthracycline capable of delivering effective anthracycline therapy without traditional cumulative dose limitations, thus further supporting its ongoing pivotal Phase 2b/3 trial in AML patients.
“This poster presentation adds significant momentum to the growing clinical evidence supporting Annamycin's differentiated profile. Anthracyclines remain among the most effective agents in oncology, yet their long-term use has historically been constrained by irreversible cumulative cardiotoxicity. These data continue to suggest that Annamycin may have the potential to fundamentally change that paradigm.”
Shepard et al. (Wed,) conducted a other in Acute myeloid leukemia (AML) and soft tissue sarcoma (n=90). L-Annamycin was evaluated on Change in LVEF from baseline to final assessment (mean difference -0.12%, 95% CI -1.34 to 1.09, p=0.84). L-Annamycin was not associated with significant changes in LVEF from baseline (mean difference, -0.12%; 95% CI, -1.34 to 1.09; p=0.84) despite high cumulative anthracycline exposure.