Checkpoint inhibitors in Hodgkin's lymphoma

• Published in: European journal of haematology Vol. 96; no. 4; pp. 335 - 343
• Main Author: Jezeršek Novaković, Barbara
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2016
• Subjects: Antibodies - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Clinical Trials as Topic; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - genetics; CTLA-4 Antigen - immunology; effectiveness; Gene Expression Regulation, Neoplastic; Hodgkin Disease - drug therapy; Hodgkin Disease - genetics; Hodgkin Disease - immunology; Hodgkin Disease - pathology; Hodgkin's lymphoma; Humans; immune checkpoint inhibitors; Lymphocyte Activation - drug effects; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - immunology; Reed-Sternberg Cells - drug effects; Reed-Sternberg Cells - immunology; Reed-Sternberg Cells - pathology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - pathology; toxicity; effectiveness; toxicity; immune checkpoint inhibitors; Hodgkin's lymphoma
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.12697

Hodgkin's lymphoma is unusual among cancers in that it consists of a small number of malignant Hodgkin/Reed–Sternberg cells in a sea of immune system cells, including T cells. Most of these T cells are reversibly inactivated in different ways and their reactivation may induce a very strong immune response to cancer cells. One way of reactivation of T cells is with antibodies blocking the CTLA‐4 and especially with antibodies directed against PD‐1 or the PD‐L1 ligand thereby reversing the tumor‐induced downregulation of T‐cell function and augmenting antitumor immune activity at the priming (CTLA‐4) or tissue effector (PD‐1) phase. Immune checkpoint inhibitors have been evidenced as an additional treatment option with substantial effectiveness and acceptable toxicity in heavily pretreated patients with Hodgkin's lymphoma. Particularly, PD‐1 blockade with nivolumab and pembrolizumab has demonstrated significant single‐agent activity in this select population.