Cancer Genetics and Epigenetics, 2025, Vol.13, No.6, 300-309 http://medscipublisher.com/index.php/cge 305 5 The Safety and Side Effects of Immune Checkpoint Inhibitors 5.1 Basic characteristics and common manifestations of immune-related side effects Immune checkpoint inhibitors have brought about a new class of side effects, known as immune-related adverse events, which are different from the side effects of traditional chemotherapy. These side effects are caused by an overly active immune system that attacks its own normal tissues, leading to inflammation or damage in different organs. The most frequently affected areas include the skin, digestive tract, endocrine glands, liver and lungs. Among them, rashes and itchy skin are usually the earliest and most common manifestations (Martins et al., 2019). Other common side effects include colitis, hepatitis, pneumonia and endocrine problems, such as hypothyroidism and pituitary inflammation. Although most side effects are mild to moderate, severe and even life-threatening situations may also occur, which require timely detection and treatment. The occurrence times of these side effects vary. Some occur within a few weeks after the start of treatment, while others appear several months later or after drug withdrawal (Wang et al., 2018). 5.2 Basic principles for grading and management of immune-related side effects At present, the general adverse event evaluation criteria are usually used to grade immune-related side effects, dividing their severity from grade 1 (mild) to grade 5 (death). This grading system is of great significance for clinical management, as it helps doctors determine whether to continue, suspend or permanently discontinue immunotherapy. For grade 1 side effects, medication can generally be continued under close observation. For grade 2 and above, treatment often needs to be suspended and glucocorticoids or other immunosuppressive drugs should be used (Brahmer et al., 2018). The handling principle emphasizes early detection and timely intervention to prevent the aggravation of side effects. Moderate to severe side effects are mainly treated with glucocorticoids. If the effect is not satisfactory, other immunosuppressants such as infliximab or mycophenolate mofetil may be used. Multidisciplinary collaboration is of great significance in handling complex cases, and patients should be fully informed and promptly report their discomfort symptoms (Brahmer et al., 2018). 5.3 Characteristics of side effects of combined therapy and key points of clinical management Combination therapy regimens, such as using nivolumab and ipilimumab together for dual immune blocking, often cause more and more severe side effects than using only one drug. Studies show that when anti-CTLA-4 and anti-PD-1 drugs are used in combination, the proportion of grade 3 and above adverse reactions may exceed 50%. Therefore, such regimens require stricter monitoring of patients and enhanced communication in order to detect and handle related side effects as early as possible. In combination therapy, dealing with side effects usually requires the earlier and more proactive use of immunosuppressive drugs. If the side effects are very severe, it may be necessary to discontinue some or all of the treatment drugs for a long time. Whether to reactivate immunotherapy after the improvement of side effects is a matter that requires careful consideration. It needs to be combined with the specific situation of the patient, comprehensively considering the risk of recurrence of side effects and the possible benefits of continued treatment. 6 New Developments in Combined Treatment Strategies 6.1 Synergistic methods of ICIs in combination with chemotherapy or targeted drugs The use of immune checkpoint inhibitors in combination with chemotherapy has become an important treatment approach for various solid tumors. Chemotherapy can help release more tumor antigens and improve the environment around the tumor, thereby further enhancing the effect of immunotherapy. Studies on non-small cell lung cancer such as KEYNOTE-189 have shown that pembrolizumab combined with platinum-based chemotherapy can prolong overall survival and progression-free survival of patients more than chemotherapy alone, and thus is regarded as one of the current important standard treatment regimens (Gandhi et al., 2018).
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