Checkpoint inhibitors in Hodgkin lymphoma

Abstract

Checkpoint blockade contributes to the immunosuppressive microenvironment in classical Hodgkin lymphoma (cHL) and in particular the interaction of Hodgkin cells and macrophages with T‑cells and natural killer cells via programmed cell death1 (PD-1) and programmed cell death1 ligand1 (PD-L1). The aim of this article is the evaluation the role and potential of checkpoint blockade in cHL as compared with the results of standard chemo- and radiotherapy. We analyzed preclinical and clinical data from phaseI and phaseII studies with checkpoint blockade in cHL. In 60-70% of patients with chemotherapy-refractory cHL, PD‑1 blockade results in responses. Overall survival is excellent and asmall number of patients achieve persistent response. Thus, the use of anti-PD‑1 monoclonal antibodies has become an important treatment approach in relapsed cHL in line with the label. The results of first-line therapy are still preliminary; initial phaseII studies using nivolumab in combination with doxorubicin (=adriamycin), vinblastin and dacarbazin (AVD) in early unfavorable or advanced stages showed response rates of up to 90%. Thus, implementing immunomodulatory approaches using PD 1‑blockade have resulted in asignificant reduction of chemotherapy. This might represent aparadigm shift in the therapy of cHL.