Controversies in the management of early-stage Hodgkin lymphoma

Positron emission tomography (PET)-adapted chemotherapy and radiotherapy approaches are currently used for the initial treatment of early-stage Hodgkin lymphoma (HL) with progression-free survival and overall survival exceeding 85% and 95%, respectively. However, despite general agreement on the prognostic value of interim PET in HL, frontline treatment approaches vary among institutions with respect to how pretreatment clinical risk factors determine treatment selection, the definition of PET negativity, which chemotherapy regimen to initiate and how many cycles to administer, and when to incorporate radiation. Furthermore, as recent trials have confirmed improved efficacy and manageable toxicity when brentuximab and checkpoint inhibitors are combined with frontline regimens such as doxorubicin, vinblastine, and dacarbazine in advanced-stage HL, these agents are now under evaluation as frontline therapy in early-stage HL. A number of issues will affect the use of these agents in early-stage HL, including the costs, early and late toxicities with these agents, patient population (favorable or unfavorable risk groups), how to incorporate them (concurrently or sequentially), and whether they can ultimately replace cytotoxic therapy with similar efficacy and fewer late effects. Future treatment paradigms for early-stage HL may change significantly once randomized studies are completed incorporating these agents into frontline therapy. Ideally, frontline use of brentuximab and checkpoint inhibitors in early-stage HL will result in improved outcomes compared with current PET-adapted approaches with decreased risks of late toxicities that continue to afflict long-term survivors of HL.