Safety, feasibility, and efficacy of anti-PD-1 therapy for the treatment of classical Hodgkin lymphoma

The clinical paradigm for treatment of classical Hodgkin lymphoma has been transformed by the use of anti-PD-1 therapy, driven by foundational work revealing near-universal 9p24.1 alterations resulting in overexpression of PD-L1 and PD-L2 on Reed-Sternberg cells. Use of PD-1 inhibitors has demonstrated remarkable clinical activity for patients with Hodgkin lymphoma. Anti-PD-1 monotherapy has demonstrated durable remissions in the relapsed/refractory setting, including a 5-year overall survival of around 70% in clinical trials. Further efforts have evaluated these treatments in various combinations and demonstrated efficacy in both the salvage setting prior to stem cell transplantation (SCT) and the relapsed/refractory setting after SCT. After such promising results, these agents were moved into the frontline setting with landmark trials such as SWOG S1826, establishing Nivo-AVD (nivolumab, doxorubicin, vinblastine, dacarbazine) as an emerging standard for advanced-stage classical Hodgkin lymphoma. Similarly, Nivo-AVD in the NIVAHL trial demonstrated remarkable efficacy in early stage, unfavorable disease. These agents have a unique mechanism of action that shows promise for patients who would otherwise be chemotherapy-ineligible. The use of these agents is also of interest in the adolescent and young adult populations who would be at risk from long-term side effects of chemotherapy or radiation. This review seeks to examine the safety, efficacy, and feasibility of anti-PD-1 therapy in classical Hodgkin lymphoma.