Hodgkin lymphoma and PD-1 blockade

Abstract

Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations at 9p24.1, resulting in increased expression of PD-1 ligands and immune evasion. Disruption of the PD-1 pathway with anti-PD-1 monoclonal antibodies (mAbs) can restore an antitumor immune response in many patients. Based on high overall response rates in cHL patients with relapsed or refractory (R/R) disease, two PD-1 mAbs, nivolumab and pembrolizumab, received accelerated approval in North America and Europe. Currently, numerous ongoing trials are combining PD-1 mAbs with rationally selected agents in the R/R setting and testing PD-1 blockade earlier in the treatment paradigm with potentially curative therapies. These trials and a rapidly improving understanding of mechanisms of immune resistance to PD-1 blockade have the potential to further improve outcomes for patients with cHL.