title: Immune checkpoint inhibitors in challenging populations.
abstract: Immune checkpoint inhibitors, including those targeting the programmed cell death 1/programmed cell death ligand 1 and cytotoxic T lymphocyte antigen 4 pathways, are revolutionizing cancer therapeutics. Both activity and toxicities largely stem from unleashing tumor- or host-specific cytotoxic T cells. Many patients seen in routine clinical practice have not qualified for or have been seriously underrepresented in immune checkpoint inhibitor clinical trials. Thus, a major gap in knowledge regarding the safety and efficacy of these agents persists in many populations, even after regulatory approval. To address this challenge, this review aggregates and synthesizes the available preclinical and clinical data surrounding immune checkpoint inhibitor therapy in challenging clinical populations to assist both academic and community oncologists in treatment decision making. Specifically, this review focuses on the safety and activity of immune checkpoint inhibitors in patients with autoimmune disorders, organ transplant patients, patients with chronic viral infections, patients with ongoing immunosuppressant use, patients with organ dysfunction, pregnant patients, patients with brain metastases, patients at extremes of age, and patients with an impaired functional status. Cancer 2017;123:1904-1911. © 2017 American Cancer Society.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Douglas B
authors.identifier: 0000-0002-6390-773X
authors.initials: DB
authors.lastname: Johnson
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: Department of Medicine, Melanoma Institute Australia, University of Sydney Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Menzies
mesh_terms: D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000150:complications; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000188:drug therapy; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D015658:HIV Infections / Q000150:complications; D006258:Head and Neck Neoplasms / Q000150:complications / Q000188:drug therapy; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000074324:Ipilimumab; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy; D008545:Melanoma / Q000150:complications / Q000188:drug therapy; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D000077594:Nivolumab; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D000077195:Squamous Cell Carcinoma of Head and Neck; D066027:Transplant Recipients
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; D007166:Immunosuppressive Agents; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab
keywords: autoimmune; elderly; ipilimumab; nivolumab; organ dysfunction; pediatrics; pembrolizumab; pregnancy; transplant