Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, including non-small cell lung cancer (NSCLC). These agents have improved clinical outcomes and have become quite an attractive alternative alone or combined with other treatments. Although ICIs are tolerated better, they also lead to unique toxicities, termed immune-related adverse events (irAEs). A reconstituted immune system may lead to dysregulation in normal immune self-tolerance and cause inflammatory side effects (irAEs). Although any organ system can be affected, immune-related adverse events most commonly involve the gastrointestinal tract, endocrine glands, skin, and liver. They can occur anytime during the treatment course and rarely even after completion. Owen and colleagues showed that approximately 30% of patients with NSCLC treated with ICIs develop irAEs. Kichenadasse et al. conducted a thorough evaluation of multiorgan irAEs, which is of particular interest because information regarding these types of irAEs is currently sparse. It is important to delineate between infectious etiologies and symptom progression during the management of irAEs. Close consultation with disease-specific subspecialties is encouraged. Corticosteroids are the mainstay of treatment of most irAEs. Early intervention with corticosteroids is crucial in the general management of immune-mediated toxicity. Grade 1–2 irAEs can be closely monitored; hypothyroidism and other endocrine irAEs may be treated with hormone supplementation without the need for corticosteroid therapy. Moderate- to high-dose steroids and other additional immunosuppressants such as tocilizumab and cyclophosphamide might be required in severe, grade 3–4 cases. Recently, increasing research on irAEs after immunotherapy rechallenge has garnered much attention. Dolladille and colleagues assessed the safety in patients with cancer who resumed therapy with the same ICIs and found that rechallenge was associated with about 25–30% of the same irAEs experienced previously (4). However, such data should be carefully considered. Further pooled analyses may be required before we conclude about ICIs’ safety in rechallenge.

Immune checkpoint inhibitors (ICIs) have rapidly shifted the landscape of treatments in malignancy with significant improvements in survival paradigm. They have been an attractive armamentarium to the oncologists given the limited immune adverse effects with potential for deeper and durable benefits that haven't been previously noticed with chemotherapy. However, they result in unique toxicities by limiting immune self-tolerance and cause immune-mediated endocrinopathies, such as hypothyroidism, pneumonitis, colitis, hepatitis, myocarditis, meningitis, hypophysitis, etc. As such, they are contraindicated in patients with autoimmune disorders or recipients of organ transplants given the risk for reactivation or flare of the underlying autoimmune disease and rejection of the donor organ in transplants, although sporadic cases have been reported with the use of immunotherapy in such patients. Malignant melanoma is a highly aggressive cancer, with only 15-20% five-year survival rate once it has spread to the lymph nodes or has distant metastasis. ICIs have changed the landscape of advanced melanoma with exponential improvements in survival, the 5-year survival rates are about 50%. Multiple sclerosis (MS) is recognized as T cell-mediated immune response causing inflammation, which causes local inflammatory plaques and demyelination. ICIs are likely to generate an immune response that causes molecular mimicry and cross-react with CNS autoantigens, in turn exacerbating pre-existing immune response and subsequent flare-ups in MS. There is little knowledge about treating such patients with immunotherapy, short of a few case reports and series; in this report, we describe another such case. We present a case of checkpoint inhibitor therapy in a patient with multiple sclerosis who underwent immune checkpoint inhibitor therapy with pembrolizumab for metastatic malignant melanoma who had a complete response to treatment at the cost of MS relapse, which was managed with high-dose steroids.