Immunotherapy-Based Therapies in Pediatric Hodgkin Lymphoma: Potential to Narrow the Gap in Long-Term Survival

Abstract

Pediatric advanced-stage Hodgkin lymphoma (HL) is highly curable, yet survivors treated with historical regimens face substantial late morbidity and excess mortality. Immunotherapy-based frontline therapies improve disease control, but late toxicities remain unknown. We developed a simulation model to project lifetime outcomes after contemporary brentuximab vedotin- or nivolumab-containing regimens using trial data (COG AHOD1331 and SWOG S1826), Childhood Cancer Survivor Study data, and national databases. We assessed how frontline and relapse therapy changes could influence long-term survival and late-effect outcomes, with sensitivity analyses to evaluate potential immunotherapy-related late mortality. Compared with expected survival at age 50 in the general population, HL survival was 86% at age 50 after historical regimens and 92-93% after contemporary immunotherapy-based therapies. Survival gains persisted unless immunotherapy-related late mortality exceeded approximately 8%. These projections suggest contemporary regimens may narrow the long-term survival gap while reducing late-effect burden.