Background: Immune-related adverse effects (irAE) are autoimmune-like toxicities caused by immune checkpoint inhibitor (ICI) treatment and often necessitate interventions such as corticosteroids, treatment interruptions/discontinuation, or hospital admission. Although ICI related irAEs are well described in literature, data on the toxicity profile associated with long-term ICI use remains limited. Since the optimal duration of therapy with ICI agents is currently unknown, it is crucial to assess the risks of long-term ICI use. Methods: This was a retrospective, observational, single-center study of adult oncology patients who received at least 1 year of programed death 1 (PD-1) inhibitor or programmed death ligand-1 (PD-L1) inhibitor treatment. The objective of this study was to characterize late-onset irAEs defined as greater than 1 year with long-term ICI treatment. Clinically significant irAEs were defined as those requiring corticosteroid treatment, hospital admission, treatment interruption or treatment discontinuation. This study included patients who received at least 1 year of nivolumab, pembrolizumab, atezolizumab or durvalumab between January 2016 and September 2021. Disease states included head and neck cancer, renal cell carcinoma, non-small cell lung cancer, and melanoma. Patients with concurrent exposure to other treatment such as chemotherapy, radiation, surgery, tyrosine kinase inhibitors and monoclonal antibodies while on ICI treatment were included in the study. Exclusion criteria included patients with treatment breaks of greater than 6 months, two malignancies undergoing active treatment, and treatment administration outside of the study center. Results: Of 282 patients assessed, 143 met study inclusion criteria. The median ICI treatment duration was 19 months (IQR 14-27). There was a 30% incidence of late-onset irAEs, of which 22% were clinically significant. Most late-onset irAEs were low in severity, as 45 (90%) were grade 1-2 and 5 (10%) were grade 3. The most common late-onset irAEs were pulmonary (8%) and gastrointestinal (7%). Univariate analysis suggests risk factors potentially associated with late-onset irAEs include concurrent exposure to additional therapies during ICI treatment and past medical history of rheumatologic disease. Conclusions: Although the optimal duration of ICI therapy is unknown, this study suggests that long-term ICI use was associated with a low but notable incidence of toxicities, of which most were low in severity.

There were no incidences of late-onset cardiovascular, renal, neurologic, or pancreatic irAEs. Seven patients experienced multiple irAEs.