Abstract 4238: Impact of age on toxicity in patients treated with anti-PD-1 therapy for melanoma

Abstract

Abstract Introduction: Immune checkpoint inhibitors (ICI) drive anti-tumor activity however, they also produce immune related adverse effects (irAEs) that mimic autoimmune disease. Different auto-immune diseases are seen across age groups such as inflammatory bowel disease in younger patients and rheumatoid arthritis in older patients. Thus, we assessed whether the types, patterns, and severity of irAEs differed by age. Methods: We reviewed electronic medical records of patients treated with ICI for melanoma. We assessed patient demographics, presence, type and severity of toxicity along with hospitalization and associated length of stay from management of irAEs. Logistic regression was used to assess risk of 1) irAEs, 2) severe irAEs, and 3) hospitalization from irAEs; Poisson regression was used to analyze length of stay (LOS) data. We extracted all cases of myocarditis, colitis, and pneumonitis from ICI from Vigibase through December 2018. Results: 455 patients from one center received anti-PD-1 for melanoma; 226 developed any irAE (49.7%), 59 developed a severe irAE (13.0%) and 54 patients required hospitalization (11.9%). Younger age was not associated with overall rate of irAEs but correlated with increased severe toxicity rate when controlling for gender, baseline performance status, season, and combination ICI (OR 0.97, 95% CI 0.95-0.99), as well as need for hospitalization (OR 0.97, 95% CI 0.95-0.99). Despite the increased severe toxicity and hospitalization for younger patients, older patients, when hospitalized, had increased LOS, (p&lt0.0001). Three patients experienced a fatal irAE (average age 68.0) compared to 63.0 for the rest of the cohort. This relationship was validated in Vigibase where patients with fatal myocarditis where older than those with non-fatal myocarditis (70.9 vs. 60.7 years, p=0.03) although there was no age difference between fatal vs. non-fatal pneumonitis cases. Toxicity types by age were also examined. Colitis and hepatitis were more common in younger patients (16% and 11% for age &lt45, vs. 7% and 2% for age &gt75) and tended to require frequent hospitalizations. In contrast, dermatitis and arthritis were more common in older patients (20% and 6% for age &gt75 compared to 12% and 1% in age <45) and rarely required admission. Heart and lung irAEs were rarer, however but occurred more often in older patients and were associated with hospitalizations and mortality. This was confirmed in 5759 patients in Vigibase where patients with colitis had a younger age distribution compared to myocarditis (χ2 p&lt0.001) and pneumonitis (p&lt0.001) when treated with combination ICI, although this relationship was not seen with ICI monotherapy. Conclusion: A novel and somewhat paradoxical relationship between age and irAEs was seen where younger patients tended to have more severe irAEs, while older patients tender to have longer hospitalizations for irAE management and increased fatality from irAEs. This may be explained by the distinct phenotypes of irAEs that occur with specific age groups. Citation Format: Kaustav P. Shah, Haocan Song, Fei Ye, Joe-Elie Salem, Justin Balko, Douglas B. Johnson. Impact of age on toxicity in patients treated with anti-PD-1 therapy for melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4238.