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.

Keywords: autoimmune; elderly; ipilimumab; nivolumab; organ dysfunction; pediatrics; pembrolizumab; pregnancy; transplant.

Conflict of interest statement

Conflicts of interest: DBJ serves on advisory boards for BMS and Genoptix, and receives research funding and travel support from Incyte. RJS has consulted/advised for Amgen, Novartis, Astex, Prometheus, and receives research funding from Merck. AMM serves on advisory boards for MSD and Chugai, and receives honoraria from BMS and Novartis.

© 2017 American Cancer Society.