Impact of Immune-Related Adverse Events on Immune Checkpoint Inhibitors Treated Cancer Patients’ Survival: Single Center Experience and Literature Review

Abstract

Immune-related adverse events have emerged as a new challenge and its correlation with survival remains unclear. The goal of our study was to investigate the effect of irAE on survival outcomes in solid tumor patients receiving ICI treatment. This was a retrospective, single-center study at a university hospital involving patients with malignancy who received immune checkpoint inhibitors. Chart review was performed on each patient, noting any irAE, including new events or worsening of previous autoimmune condition after starting treatment with ICI. A total of 155 patients were included, 118 (76.1%) were male, with median age of 64 years. Median follow up time was 36 months. Seventy patients (45.2%) had at least one irAE. Of all irAE, nine (8.1%) were classified as grade 3 or higher according to the CTCAE version 5.0. There was one death secondary to pneumonitis. Median ICI cycles until first irAE onset was 4 (range: 2–99). The objective response rate was higher for patients who developed irAE (18.7% vs. 9.0%; p = 0.001), as was median overall survival (18 months (95% CI, 8.67–27.32) vs. 10 (95% CI, 3.48–16.52) months; p < 0.016) and progression free survival (10 months (95% CI, 5.44–14.56) vs. 3 months (95% CI, 1.94–4.05); p = 0.000). The risk of death in patients with irAE was 33% lower when compared to patients without such events (hazard ratio (HR): 0.67; 95% CI, 0.46–0.99; p = 0.043). Development of irAE predicted better outcomes, including OS in patients with advanced solid tumors treated with ICI. Further prospective studies are needed to explore and validate this prognostic value.

Case Report: A Presentation of Early-Onset Immune-Mediated Bullous Pemphigoid in a Patient with Urothelial Cancer

“…Raquel Romão et al conducted a study in 2023 on 155 tumor patients receiving ICIs. Patients who developed irAE gave a higher objective response rate (ORR) (18.7%), and the risk of death was 33% lesser than patients without irAEs [ 45 ]. A recent meta-analysis by Zhao et al of 789 cases of re-exposure to ICIs suggests that despite the fact that retreatment with ICIs is associated with a higher recurrence of irAEs, no higher number of high-grade irAEs or less efficacy is observed [ 46 ].…”

Vitiligo-like Lesions as a Predictor of Response to Immunotherapy in Non-Small Cell Lung Cancer: Comprehensive Review and Case Series from a University Center

“…Many reports have examined the prognostic impact of irAE regarding cancer outcomes, and even its predictive value in defining the probability of response to ICI. Most published data suggest that patients who developed irAE exhibited a reduced risk of death or progression among different primary tumors, namely malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract [38,39]. An exceptional significant association between irAE and ICI efficacy in patients with cancer has been attributed to dermatological events (vs. other irAEs), and to anti-PD-(L)1-treated patients (vs. CTLA4 inhibitors) [40].…”

Immunotherapy-Associated Atherosclerosis: A Comprehensive Review of Recent Findings and Implications for Future Research

“…Several studies have reported that even low levels of steroids confer an increased risk of ASCVD in these patients when used chronically [148][149][150]. From an oncologic standpoint, some studies raise the concern that steroids may blunt ICI treatment response, though this is not entirely clear [151][152][153][154][155][156]. Overall, steroids are not recommended for prevention or treatment of ICI-mediated ASCVD, and more research on targeted steroid-sparing therapies is needed.…”