Immune checkpoint inhibitors (ICI) have transformed oncology practice, however serious immune-related adverse events (irAE) occur and are poorly understood. A correlation between irAE and clinical benefit has been suggested in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). The incidence of irAEs has been described in clinical trials but risks factors remain undefined. This study reports the incidence and risks factors of irAE in patients (pts) with multiple cancers treated with any ICI, as well as overall survival.
A retrospective study of pts with any malignancy treated with ICI (alone or in combination) between January 2010 and June 2017 was carried out at The Ohio State University. Grade > = 2 irAEs were abstracted based on the treating physician diagnosis. Overall survival (OS) was calculated from the date of initiation of ICI to death from any cause or date of last follow-up. The associations between irAE incidence and categorical outcomes were studied using chi-square or Fisher’s exact test. The Wilcoxon test was used for continuous outcomes. Survival outcomes were studied using log-rank test or cox regression model.
Of 1,113 pts identified, 417 pts had complete irAE data: 156 pts with melanoma, 117 pts with NSCLC, 33 pts with RCC, and 111 pts with other cancers. irAEs occurred in 120/417 pts (28.78%). Gender, age at treatment, and smoking history were not associated with irAE. Incidence of pneumonitis and colitis were 3.84% and 6%, respectively. Pneumonitis was more common in NSCLC (p = 0.004), and colitis was more common in melanoma (p = 0.016). Rates of thyroid, hepatic, and neurologic irAE were 5.29%, 4.08%, and 0.84%. irAEs were associated with length of therapy (p = 0.021), and were more common in 29 pts treated with combination ICI (p < 0.001). For 366 pts with metastatic disease, irAEs were associated with longer survival: median OS 21.1 months vs 9.2 months (HR = 0.48, 95% CI: 0.35 - 0.66, p < 0.001). Thyroid toxicity (HR = 0.25, 95% CI: 0.10 – 0.29, p = 0.002) and hepatitis (HR = 0.32, 95% CI: 0.12 – 0.85, p = 0.023) were associated with longer OS.
Increased awareness of irAE patterns across different cancer and treatment types will allow for rapid identification and treatment of irAE.
Clinical trial identification
Legal entity responsible for the study
The Ohio State University.
Has not received any funding.
G. Tinoco: Advisory board: Blueprint. E.M. Bertino: Advisory board: Takeda, Boehringer Ingelheim. D.P. Carbone: Research funding: BMS; Paid advisory boards: Merck, BMS, AZ, Genentech. All other authors have declared no conflicts of interest.