Pediatric Hodgkin Lymphoma Trials Show Net Reduction in Late Cardiotoxicity

Changes to modern treatment protocols for pediatric Hodgkin lymphoma (HL) seem to have reduced late cardiotoxicity, according to a study published in JAMA Network Open.

Researchers found that Children’s Oncology Group (COG) trials have reduced the proportion of children with HL who receive mediastinal radiotherapy (RT), reduced the mean RT dose to the heart, and increased pharmacologic cardioprotection with dexrazoxane. These factors appear to have offset the effects of increasing the cumulative dose of doxorubicin.

With this analysis, researchers sought to estimate the risk of cardiotoxicity associated with modern treatment approaches in HL clinical trials. The study included data from 2563 patients with HL treated in 4 COG trials from 2002 to 2022.

Over the course of the trials, the proportion of patients receiving mediastinal RT decreased from 61.8% to 0.4% (P <.001), and the mean heart dose among patients who did receive RT decreased from 13.2 Gy to 3.8 Gy (P <.001).

Greater mean cardiac RT dose was associated with an increased risk of any cardiac disease (hazard ratio [HR], 1.40 per 10 Gy; 95% CI, 1.26-1.55; P <.001), coronary artery disease (HR, 1.43 per 10 Gy; 95% CI, 1.26-1.62; P <.001), and heart failure (HR, 1.59 per 10 Gy; 95% CI, 1.36-1.86; P <.001).

The researchers also found that use of dexrazoxane increased over the course of the trials, with 0% of patients receiving it in the first trial (which enrolled patients in 2002-2009) and 79.3% receiving it in the last trial (enrolling in 2019-2022).

The cumulative doxorubicin dose also increased from 200 mg/m² to 300 mg/m² over the course of the trials. A greater dose of doxorubicin was associated with an increased risk of heart failure (HR, 1.49 per 100 mg/m²; 95% CI, 1.31-1.69; P <.001).

The researchers estimated that the 30-year cumulative incidence of grade 3-5 cardiac disease among 15-year-old patients in the AHOD0031 trial, which enrolled patients during 2002-2009, was 9.6% in the standard treatment arm and 8.0% in the experimental arm.

The incidence was 8.6% in the AHOD0831 trial (enrolling in 2009-2012), 8.2% in the AHOD1331 trial (enrolling in 2015-2019), and 6.2% in the S1826 trial (enrolling in 2019-2022).

In comparison, the expected 30-year cumulative incidence of cardiac disease in an untreated population was 5.0%.

“These findings suggest that evolutions in HL treatment are associated with a net reduction in late cardiac disease,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor