PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma

• Published in: The New England journal of medicine Vol. 372; no. 4; pp. 311 - 319
• Main Authors: Ansell, Stephen M, Lesokhin, Alexander M, Borrello, Ivan, Halwani, Ahmad, Scott, Emma C, Gutierrez, Martin, Schuster, Stephen J, Millenson, Michael M, Cattry, Deepika, Freeman, Gordon J, Rodig, Scott J, Chapuy, Bjoern, Ligon, Azra H, Zhu, Lili, Grosso, Joseph F, Kim, Su Young, Timmerman, John M, Shipp, Margaret A, Armand, Philippe
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 22.01.2015
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Apoptosis; Autografts; Blocking antibodies; Body weight; Cancer; Chromosome 9; Drug therapy; Female; Hodgkin Disease - drug therapy; Hodgkin Disease - metabolism; Hodgkin Disease - therapy; Hodgkin's lymphoma; Humans; Immunoconjugates - therapeutic use; Immunotherapy; Janus kinase; Janus Kinases - metabolism; Ligands; Lymphoma; Male; Medical research; Middle Aged; Monoclonal antibodies; PD-1 protein; PD-L1 protein; PD-L2 protein; Programmed Cell Death 1 Ligand 2 Protein - metabolism; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - metabolism; Recurrence; Reed-Sternberg cells; Reed-Sternberg Cells - drug effects; STAT Transcription Factors - metabolism; Stat3 protein; Stem Cell Transplantation; Targeted cancer therapy; Tomography; Toxicity; Transcription; Transplants & implants; Tumors; United States > US
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1411087

In a small series of patients with refractory Hodgkin's lymphoma, a substantial rate of tumor regression (87%) was documented in response to blockade of the programmed death 1 pathway. The programmed death 1 (PD-1) pathway serves as a checkpoint to limit T-cell–mediated immune responses. 1 Both PD-1 ligands, PD-L1 and PD-L2, engage the PD-1 receptor and induce PD-1 signaling and associated T-cell “exhaustion,” a reversible inhibition of T-cell activation and proliferation. 1 By expressing PD-1 ligands on the cell surface and engaging PD-1 receptor–positive immune effector cells, tumors can co-opt the PD-1 pathway to evade an immune response. 2 PD-1–blocking antibodies have been used to enhance immunity in solid tumors and obtain durable clinical responses with an acceptable safety profile. 2 – 5 Preliminary data also support empirical PD-1 blockade as a therapeutic strategy . . .