Considerations for immunotherapy in patients with cancer and comorbid immune dysfunction

Immune checkpoint inhibitors have been widely incorporated for cancer treatment in a variety of solid and hematologic malignancies. Multiple clinical trials have demonstrated the efficacy of PD-1/PD-L1 and CTLA-4 axis inhibition in the metastatic and adjuvant settings. Due to the risks of autoimmune toxicity with these agents, stringent inclusion/exclusion criteria were employed in those initial clinical trials. These criteria led to exclusion or underrepresentation of a variety of patient populations with underlying immune dysfunction. These populations included patients with preexisting autoimmune diseases, solid organ or bone marrow transplant recipients, patients with HIV or viral hepatitis infections, patients receiving concurrent chronic steroid therapy, as well as patients who were elderly, pregnant, or had poor performance status. Thus, established guidelines on the use of immune checkpoint inhibitors in these patients are lacking, and evidence to support efficacy or toxicity are overall limited to retrospective studies and case series. Fortunately, ongoing clinical trials are now including these patients and are shedding light on whether these underrepresented populations can also safely benefit from immune checkpoint inhibitor therapies. In this review, we summarize the most clinically relevant available data on the use of checkpoint inhibitors in immunocompromised patient groups with a primary focus on safety.