Dexrazoxane preserves cardiac function without compromising survival in pediatric AML
Dexrazoxane preserved cardiac function without compromising EFS and OS among pediatric patients undergoing chemotherapy for acute myeloid leukemia, according to prospective study results.
The drug also did not increase noncardiac toxicities and should be considered for cardio-protection during front-line treatment of pediatric AML, researchers noted.
“To our knowledge, these data are the first demonstration of a potential survival benefit with dexrazoxane, specifically a reduction in treatment-related mortality,” Kelly D. Getz, PhD, MPH, assistant professor of epidemiology in the department of biostatistics, epidemiology and informatics at Perelman School of Medicine at University of Pennsylvania, said in a press release. “This suggests that dexrazoxane may directly prevent acute, severe cardiac events that contribute to early deaths. Additional research to understand the underlying biology of anthracycline-associated cardiotoxicity and elective interventions will improve both the cardiovascular and oncologic outcomes for children with cancer.”
Anthracycline intensication has improved OS in pediatric AML. However, anthracyclines increase both early- and late-term cardiotoxicity, according to study background.
Within 1 year of starting therapy, at least 12% of patients with AML experience left ventricular systolic dysfunction (LVSD). Many have reduced 5-year EFS and OS, as well as higher treatment-related mortality.
Getz and colleagues sought to assess the effectiveness of dexrazoxane — a cardioprotective drug that interferes with iron-mediated free radical formation and cell death caused by anthracyclines — among 1,014 pediatric patients with AML and without high allelic ratio FLT3/internal tandem duplication who underwent treatment in the AAML1031 Children’s Oncology Group trial.
Among the patients, treated between 2011 and 2016, 96 were exposed to dexrazoxane at every anthracycline course and 918 were never exposed.
Distributions of sex, age, race, risk group, treatment group, white blood cell count and compliance with cardiac monitoring appeared similar in both groups.
Researchers analyzed occurrence of LVSD, trends in ejection fraction and shortening fraction, 5-year EFS and OS, and treatment-related mortality.
Median follow-up was 3.5 years.
Results showed dexrazoxane-exposed patients had smaller ejection fraction and shortening fraction declines than patients who did not receive the drug across courses, as well as a lower risk for LVSD (26.5% vs. 42.2%; HR = 0.55; 95% CI, 0.36-0.86).
The dexrazoxane-exposed and unexposed groups had similar 5-year EFS (49% vs. 45.1%) and OS (65% vs. 61.9%). Patients who received dexrazoxane, however, had lower treatment-related mortality (5.7% vs. 12.7%), although the difference did not reach statistical significance.
A lack of randomization served as a limitation to this study.
“This study provides important evidence that using dexrazoxane helps prevent heart damage in children undergoing treatment for AML,” Richard Aplenc, MD, PhD, MSCE, professor of pediatrics in the department of pediatrics and core faculty member of the Center for Pediatric Clinical Effectiveness at Children’s Hospital of Philadelphia, said in a press release. “These results have arguably changed the standard of care for pediatric AML treatment.” – by John DeRosier
Disclosures: Aplenc reports honoraria and travel accommodations from Sigma-Tau. Getz reports no relevant financial disclosures. Please the study for all other authors’ relevant financial disclosures.