Targeted immunotherapy in the treatment of childhood and adolescent classic Hodgkin lymphoma.

Childhood and adolescent classic Hodgkin Lymphoma (cHL) has long been a model for how we balance improved outcomes with increased toxicities in pediatric cancer. The recognition that unacceptable short- and long-term toxicities come with increasing intensity of treatment has led to a decades-long attempt to better understand the patient-specific factors that dictate responses and outcomes. Targeted immunotherapy has emerged as a promising adjunct to cancer treatment; it has been shown to improve outcomes for poorly responding patients, to salvage relapsed disease, and more recently, to replace more toxic therapy modalities such as chemotherapy and radiation while maintaining excellent outcomes. Targeted antibody therapy for cHL--whether it be naked, conjugated, or bispecific--has been proven effective and well tolerated in the pediatric population. Targets include both Reed-Sternberg cells and the tumor microenvironment, and therapy can be directed against cell surface proteins or immune checkpoint blockade. Ongoing adult and pediatric cell therapy trials in which CD30-targeting chimeric antigen receptor T-cell therapy is used for patients with relapsed or refractory disease will determine the best approaches for these high-risk patients. As a result of innovations in tumor biology, the development of novel immunotherapy agents, and a better understanding of toxicities, targeted immunotherapy is now a component not only of the treatment of pediatric cHL but also of cancer treatment paradigms overall.