Dexrazoxane may provide effective cardiovascular protection to pediatric patients undergoing chemotherapy for acute myeloid leukemia (AML), according to study results published in the Journal of Clinical Oncology.

Within 1 year of starting treatment, more than 12% of patients with AML experience left ventricular systolic dysfunction (LVSD) and significant decreases in 5-year event-free survival and overall survival (OS) with higher treatment-related mortality (TRM). Kelly D. Getz, PhD, MPH, of the Children’s Hospital of Philadelphia and the University of Pennsylvania, and colleagues conducted a multicenter study to determine whether the use of dexrazoxane, which interferes with iron-mediated free radical formation and inhibits apoptotic effects on cardiomyocytes by anthracyclines, could mediate the risk of LVSD.

The study was part of the Children’s Oncology Group trial AAML1031 (ClinicalTrials.gov Identifier: NCT01371981) between 2011 and 2016 and examined a multicenter cohort of 1014 pediatric patients (<30 years of age) with AML without high allelic ratio FLT3/ITD. Median follow-up time was 3.5 years. Ejection fraction (EF) and shortening fraction (SF) were recorded after each course and at regular intervals in follow-up. According to study protocol, anthracyclines to be withheld from patients if there was evidence of LVSD, which was defined as SF less than 28% or EF less than 55%. Of the cohort, 96 patients were exposed to dexrazoxane at every anthracycline cycle, 78 patients received dexrazoxane during some anthracycline courses, and 918 patients were never exposed. Primary analyses only measured outcomes in patients who consistently received dexrazoxane and those who never received it.

Both dexrazoxane-exposed and unexposed patients had similar distributions of sex, age, race, presenting white blood cell count, risk group, treatment arm, and compliance with cardiac monitoring. Patients exposed to dexrazoxane had significantly smaller declines in EF and SF compared with unexposed patients across courses and a lower risk of LVSD (26.5% vs 42.2%, respectively; hazard ratio, 0.55; P =.009). Additionally, 5-year event-free survival rate and OS rate were similar between the 2 groups (65.0% vs 61.9%, respectively).

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In the primary analysis, patients exposed to dexrazoxane had lower treatment-related mortality compared with unexposed patients (5.7% vs 12.7%; P =.068); however, in intention-to-treat sensitivity analyses, the rate of treatment-related mortality was significantly less among patients who were exposed to dexrazoxane (P =.024).

Limitations include confounding biases, inability to perform a randomized clinical trial given the rarity of pediatric AML and resource limitations.

Overall, the authors concluded that the findings support dexrazoxane use in pediatric AML to reduce short-term anthracycline-associated cardiac dysfunction.

“A more complete understanding of the underlying biology of anthracycline-associated cardiotoxicity and effective interventions will improve both the cardiovascular and the oncologic outcomes for children with cancer,” the authors concluded.

Reference

Getx KD, Sung L, Alonzo TA, et al. Effect of dexrazoxane on left ventricular systolic function and treatment outcomes in patients with acute myeloid leukemia: a report from the Children’s Oncology Group [published online April 28, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.02856.