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BACKGROUND: Immune checkpoint inhibitors are a relatively new advancement in the world of cancer therapy. As such, their adverse effects have yet to be fully understood, with only recent literature documenting autoimmune phenomena secondary to their utilization. Specific immune checkpoint inhibitors have recently been linked with the development of myasthenia gravis, which is classically known to manifest spontaneously in patients. Given the relative rarity of this presentation, the risk of misdiagnosis and subsequent mortality and morbidity is concerning.
METHODS: We discuss the case of a 73-year-old male who presented with clinical symptoms of myasthenia gravis and myositis shortly after beginning treatment with Pembrolizumab. The diagnosis of myasthenia gravis was initially missed at an outside hospital, which delayed initiation of proper treatment.
CONCLUSIONS: While the incidence of \"de-novo\" diseases secondary to immune checkpoint inhibitors might be increasing, guidelines regarding best treatment options do not yet exist, leaving many providers at a loss when faced with making clinical decisions surrounding patients with De novo myasthenia gravis. Thus, our goal is to underscore the importance of early recognition of this disease, and emphasize the need for a standard of care as immune checkpoint inhibitors usage becomes more prevalent.

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The recently approved immunotherapeutic drugs are Keytruda (pembrolizumab) and Imfinzi (durvalumab) for advanced biliary tract cancers that inhibit PD-1 receptor and PD-L1 ligand, respectively. In this perspective, the results of the two clinical trials, i.e., TOPAZ-1 (NCT03875235) and KEYNOTE-966 (NCT04003636), are critically appraised, compared, and discussed to assess the benefits of these two drugs in the context of the treatment of advanced biliary tract cancers with a focus on PD-L1 status and MIS (microsatellite instability) status and therapy responsiveness in the subgroups. Analyzing the PD-L2 status in biliary tract cancer patients can aid in assessing the prognostic value of PD-L2 expression in determining the clinical response and this may aid in appropriate patient stratification.

BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors such as pembrolizumab, has become an important tool in personalized cancer therapy. These inhibitors target proteins on T-cells that regulate the immune response against tumor cells. Pembrolizumab, which targets the programmed cell death 1 receptor on T-cells, has been approved for the treatment of metastatic melanoma and non-small cell lung cancer. However, it can also lead to immune-related side effects, including pneumonitis, colitis, thyroid abnormalities, and rare cases of type 1 diabetes.
METHODS: The case presented involves an adult patient in 30s with breast cancer who developed hyperglycemia after receiving pembrolizumab treatment. The patient was diagnosed with diabetic ketoacidosis and further investigations were performed to evaluate for new-onset type 1 diabetes. The patient had a history of hypothyroidism and a family history of breast cancer. Treatment for diabetic ketoacidosis was initiated, and the patient was discharged for close follow-up with an endocrinologist.
CONCLUSIONS: This literature review highlights the occurrence of diabetic ketoacidosis and new-onset type 1 diabetes in patients receiving pembrolizumab treatment for different types of cancer. Overall, the article emphasizes the therapeutic benefits of immunotherapy in cancer treatment, particularly pembrolizumab, while also highlighting the potential side effect of immune-related diabetes that can occur in a small percentage of patients. Here we present a case where pembrolizumab lead to development of diabetes after a few cycles highlighting one of the rare yet a serious toxicity of the drug.

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Immune checkpoint inhibitors (ICIs), pembrolizumab in particular, have been shown to be vastly more efficacious than traditional cytotoxic or platinum-based chemotherapies in the treatment of non-small cell lung cancer (NSCLC). While there are plenty of data showing their efficacy and safety profiles, very little exists about the long-term effects of pembrolizumab. We compiled all patients with NSCLC who were treated with pembrolizumab at our institution and had progression-free survival (PFS) of at least 2 years during or after the treatment period. Within this group, we examined the long-term rates of PFS and overall survival (OS), side effect profiles, treatment, and overall disease course up to 60 months after starting treatment. This study included 36 patients with median (range) follow up times from treatment initiation in months as follows: 36 (28-65) overall; 39.5 (28-65) for adenocarcinoma; and 36 (30-58) for squamous cell carcinoma. The median (range) of OS and PFS (months) was comparable for adenocarcinoma, 36 (23-55); and squamous cell carcinoma, 35.5 (28-65). Overall, pembrolizumab shows remarkable long-term safety and efficacy in NSCLC patients. In patients who show an initially strong response and can make it to 24 months of PFS, disease progression after this period seems increasingly unlikely.

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