A Real-World Comparison of the Safety Profile for Immune Checkpoint Inhibitors in Oncology Patients

Background/Objectives: Owing to the growing use of immune checkpoint inhibitors (ICIs) in the treatment of cancer, a wide spectrum of toxicity has arisen among cancer patients. Yet, limited ICI toxicity-related research is currently conducted in our region. Methods: This is a retrospective observational study conducted on adult cancer patients who received at least one cycle of ICI single therapy. Toxicity profiles of different ICI monotherapies were described and compared, and their association with different risk factors was assessed. SPSS version 28 was used for statistical analyses, and p < 0.05 was considered statistically significant. Results: A total of 428 patients were treated with anti-PD1 (nivolumab [n = 221, 51.6%] and pembrolizumab [n = 126, 29.5%]) or anti-PD-L1 (atezolizumab [n = 78, 18.2%] and durvalumab [n = 3, 0.7%]). Pneumonia was the most common complication (10%), followed by acute kidney injury (AKI; 8.2%) and hepatitis (7.9%). The proportion of hepatitis cases was significantly higher among atezolizumab compared to nivolumab-, pembrolizumab-, and durvalumab-treated patients (17.95% vs. 7.7% vs. 2.4% vs. 0.0%, respectively; p < 0.001). Gastrointestinal complication (colitis) was detected in 3.3% of patients with a significant difference between treatment groups (4.5%, 1.6%, 1.3%, and 33.3% in nivolumab, pembrolizumab, atezolizumab, and durvalumab, respectively; p = 0.008). Cardiac complications occurred in 1.2% of patients with a significant difference between treatment groups (0.5% in the nivolumab, 3.8% in the atezolizumab, 33.3% in the durvalumab, and none in the pembrolizumab groups (p < 0.001)). Musculoskeletal side effects, including both arthralgia and fatigue, were the most-reported side effects by 39.5% of patients, with significantly higher arthralgia complainers only in nivolumab (7.7%) compared to other treatment groups (0%, 2.6%, and 0% in pembrolizumab, atezolizumab, and durvalumab, respectively, p = 0.007). Hepatic, cardiovascular, hematological, respiratory, renal, gastrointestinal complications, thyroid complications, and dermatological side effects were found to occur on weeks 6, 7.5, 8, 8, 10, 10, 10.5, and 12 after treatment initiation, respectively, with no significant difference between treatment groups. Despite that, hepatitis and AKI tended to occur earlier with atezolizumab (week 2, p = 0.084) and pembrolizumab (week 2, p = 0.062), respectively, compared to their comparators. The female gender and a history of hepatitis were found to increase the odds of hepatic complication with anti-PD1 or anti-PD-L1 use [OR = 2.71; 95% CI 1.07-6.85, OR = 11.14; 95% CI 3.46-35.88, respectively]. Previous exposure to cancer therapy only was found to increase the odds of developing pneumonia among the treated patients [OR = 3.08; 95% CI 1.12-8.85]. Having hematological malignancy influenced the odds of hematological complications positively (either neutropenia or thrombocytopenia) compared to solid malignancies when patients were treated with anti-PD1 or anti-PD-L1 [OR = 17.18; 95% CI 4.06-72.71]. Finally, the female gender was found to positively associate with the odds of nausea/vomiting and fatigue secondary to anti-PD1 or anti-PD-L1 administration [OR = 2.08; 95% CI 1.34-3.21, OR = 1.65; 95% CI 1.09-2.51, respectively]. On the other hand, previous exposure to cancer therapy was found to reduce the risk of having arthralgia with anti-PD1 or anti-PD-L1 administration [OR = 0.344; 95% CI 0.121-0.974]. Conclusions: Treatment with anti-PD1 or anti-PD-L1 was associated with a spectrum of complications and side effects. Several risk factors have been identified to impact their occurrence. ICI toxicities and risk factors influencing their odds should be recognized and considered in clinical practice, as this could help in individualizing therapeutics regimens and avoiding treatment interruption.