More than 80% of patients with advanced-stage Hodgkin lymphoma are now cured with contemporary treatment approaches. The ongoing challenge is how to further improve outcomes by identifying both high-risk patients who may benefit from more intensive frontline therapy to reduce the risk of relapse as well as lower-risk patients who may do just as well with less intensive therapy. Numerous trials have used an interim positron emission tomography (PET) response-adapted approach to evaluate early escalation or deescalation of therapy for patients with a positive or negative interim PET scan, respectively. Recent trials have incorporated novel agents, including brentuximab vedotin (BV) and the immune checkpoint inhibitors, in the frontline setting. Based on results of the ECHELON-1 trial, the Food and Drug Administration approved BV in combination with adriamycin, vinblastine, and dacarbazine chemotherapy for stage III to IV Hodgkin lymphoma. Improved methods to assess higher risk at diagnosis using quantitative PET metrics, such as metabolic tumor volume and total lesion glycolysis, and incorporation of emerging biomarkers may further refine patient selection for more intensive upfront therapy. The ultimate goal is to achieve the highest level of efficacy for an individual patient while minimizing the short- and long-term toxicities.

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