title: Pembrolizumab in classical Hodgkin's lymphoma.
abstract: Pembrolizumab is a humanized monoclonal antibody directed against programmed cell death protein 1 (PD-1), a key immune-inhibitory molecule expressed on T cells and implicated in CD4+ T-cell exhaustion and tumor immune-escape mechanisms. Classical Hodgkin's lymphoma (cHL) is a unique B-cell malignancy in the sense that malignant Reed-Sternberg (RS) cells represent a small percentage of cells within an extensive immune cell infiltrate. PD-1 ligands are upregulated on RS cells as a consequence of both chromosome 9p24.1 amplification and Epstein-Barr virus infection and by interacting with PD-1 promote an immune-suppressive effect. By augmenting antitumor immune response, pembrolizumab and nivolumab, another monoclonal antibody against PD-1, have shown significant activity in patients with relapsed/refractory cHL as well as an acceptable toxicity profile with immune-related adverse events that are generally manageable. In this review, we explore the rationale for targeting PD-1 in cHL, review the clinical trial results supporting the use of checkpoint inhibitors in this disease, and present future directions for investigation in which this approach may be used.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Arthur G James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Maly
authors.affiliation: Division of Hematology, Department of Internal Medicine, Arthur G James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Lapo
authors.initials: L
authors.lastname: Alinari
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D008024:Ligands; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D019139:Tumor Escape
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008024:Ligands; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab
keywords: Hodgkin's lymphoma; immune checkpoint inhibitors; pembrolizumab