Pembrolizumab is an immune checkpoint inhibitor that blocks the PD1 receptor and is currently used in the treatment of a vast variety of malignancies. Despite adrenal insufficiency already being documented as a rare but potential side effect, its diagnosis is usually delayed due to its vague presentation, increasing the risk of deleterious outcomes. We present a case of secondary adrenal insufficiency while on pembrolizumab, in which the diagnosis was delayed due to a nonspecific clinical picture. This case highlights the importance of maintaining a high index of suspicion for endocrine dysfunction in patients treated with immune checkpoint inhibitors, as early recognition and appropriate intervention are paramount to preventing serious complications in these patients.

Immune checkpoint inhibitors (ICIs) have completely changed cancer treatment in the last decade and are now widely used in several cancers. In the era of immunotherapy, oncologists have changed not only the way they evaluate treatment efficacy but also the management of treatment-related adverse events. This new profile of immune adverse events has resulted in an urgent need for a more holistic view of cancer patients and for more collaborations with other organ specialists to optimize patient treatment and support. The anti-programmed death-ligand 1 antibody, avelumab, has been widely used as a maintenance treatment in stage IV urothelial carcinoma since the results from the Javelin 100 bladder trial were published. We report a case of a 75-year-old man with stage IV urothelial carcinoma submitted to first-line platinum-based chemotherapy followed by maintenance avelumab. He achieved a complete bone and pulmonary response 10 months after stopping avelumab, which was suspended due to a serious immune adverse event, an ICI-induced type 1 diabetes mellitus. At present, the patient has an overall survival of 24 months and shows no evidence of disease with a good quality of life 16 months after avelumab suspension. We hypothesized that a late response to avelumab could explain this unexpected outcome.

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Bone metastases is prevalent from renal cell carcinoma (RCC) with poor quality of life and prognosis. Our previous proteomics analysis identified dysregulated proteins in the bone-tropism RCC cells. In this study, we further examined the clinical implications of these proteins using multiple clinical cohorts. We identified 6 proteins with significant upregulation in RCC tumor tissue in comparing to tumor adjacent normal tissue (p<0.05). High expression of these 6 protein-encoding genes significantly correlates with a poor survival in the TCGA-KIRC (Kidney renal clear cell carcinoma) cohort (log-rank test p=2.7e-05), and they all individually had a reverse-correlation with the gene expression of VHL and PBRM1 (p<0.001), and positive-correlation with the expression of VEGFA (p<0.001). Further gene set variation analysis (GSVA) revealed positive correlation with Th17 cells enrichment and negative CD8 T cell infiltration in the RCC tumor microenvironment. High expression of these 6 genes in pretreatment tumors favors longer overall survival (OS)(p=0.027) in anti-PDL1 treated patients (n=428). We treated one humeral metastases RCC patient with the anti-PDL1 antibody drug atezolizumab after examined the elevated expression of the 6 proteins in his nephrectomy tumor tissue, the tumor at the fracture site shrunk remarkably after four courses of treatment. These results altogether suggest a clinical implication of the 6-protein signature in RCC bone metastasis prognosis and response to immune-checkpoint inhibitor treatment.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet they come with a spectrum of immune-related adverse events, including cardiac complications. We present the case of a 72-year-old male with metastatic renal cell carcinoma who developed complete heart block and ventricular arrhythmias following pembrolizumab therapy. Despite no evidence of myocarditis, the patient\'s condition rapidly deteriorated, ultimately resulting in his demise. This case underscores the critical need for vigilance in recognizing and managing potential cardiotoxicity associated with ICIs. Additionally, it highlights the importance of multidisciplinary collaboration in optimizing diagnostic and therapeutic strategies for patients undergoing immune checkpoint inhibitor therapy.

Combined hepatocellular cholangiocarcinoma is a rare and challenging primary liver malignancy that lacks any established standard treatments for unresectable cases. We herein present the first known case of a 49-year-old woman diagnosed with unresectable combined hepatocellular-cholangiocarcinoma, who underwent novel chemotherapy involving durvalumab plus tremelimumab combination therapy. The treatment was temporarily discontinued owing to immune-related adverse events, such as rash, and the patient was subsequently managed with systemic steroid therapy; however, the disease progressed after two courses of this treatment. Further studies are needed to validate the efficacy and safety of immune checkpoint inhibitors such as durvalumab and tremelimumab for the treatment of unresectable combined hepatocellular cholangiocarcinoma.

Tumor immunotherapy is an important clinical strategy for the treatment of various solid and hematological malignancies, and its use is on the rise. Immune checkpoint inhibitors (ICIs) are immunotherapies that boost anticancer immune responses by targeting receptors on the surface of T-lymphocytes. Two important ICIs are anti-programmed death ligand-1 (anti-PD-L1) monoclonal antibodies and anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) monoclonal antibodies. Tremelimumab (anti-CTLA-4) and durvalumab (anti-PD-L1) have been shown to be effective monotherapies. However, their combination has demonstrated effective and encouraging antitumor activity with manageable safety in patients with unresectable hepatocellular carcinoma. We present the case of an 80-year-old male with hepatocellular carcinoma who had undergone drug-eluting bead transarterial chemoembolization (DEB-TACE) on three occasions and had been started on a combination of ICIs, durvalumab, and tremelimumab. He subsequently developed various immune-related adverse effects in different organ systems, including hepatic and cardiovascular complications. Appropriate treatment was administered, but ultimately, he passed away. We aim to discuss the initial evaluation for suspected immune-related adverse events, specifically those related to myocarditis and its various manifestations, prognosis, and treatment.

The advent of immune checkpoint inhibitors has revolutionized cancer therapy by leveraging the body\'s immune system to combat malignancies effectively. Among these groundbreaking agents, programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have emerged as pivotal therapeutic approaches. PD-L1, a key protein expressed on the surface of various cells, including cancer cells, plays a central role in immune regulation by interacting with the programmed cell death protein 1 (PD-1) receptor on T-cells leading to immune suppression. The substantial increase in PD-L1 expression on cancer cell surfaces has driven the exploration of PD-1/PD-L1 inhibitors as potential immunotherapeutic agents. These inhibitors are monoclonal antibodies designed to impede the PD-L1 and PD-1 interaction and disrupt the immunosuppressive signal, thereby reinvigorating the anti-tumor immune response mediated by activated T-cells. Clinical trials investigating PD-1/PD-L1 inhibitors have demonstrated remarkable efficacy in the treatment of diverse advanced or metastatic cancers, including leukemia, non-small cell lung (NSCLC), hepatocellular, melanoma, gastric, colorectal, and breast cancers, among others. Regulatory approvals have been granted for both monotherapy and combination therapy with other cancer treatments, encompassing chemotherapy and additional immune checkpoint inhibitors. While PD-1/PD-L1 inhibitors have exhibited significant success, they are not devoid of challenges. The emergence of intrinsic or acquired resistance, as well as immune-related adverse events, warrants thorough investigation and management. Consequently, researchers have embarked on combination trials to augment the therapeutic potential of PD-1/PD-L1 inhibitors and surmount resistance mechanisms.

Novel cancer therapies have revolutionized the management of various cancers. An immune checkpoint inhibitor (ICI) is one of these antitumor medications. ICIs, which are immune therapies, enhance the immune system\'s capacity to fight cancer cells. Based on the receptors that they inhibit, such as PD-1, PD-L1, and CTLA-4, ICIs are subdivided. Although this class of drugs is extremely beneficial for cancer patients, their adverse effects can be fatal. Multiple organs, such as the cardiovascular system, may be impacted by immune-related adverse effects (irAEs). These cardiotoxic irAEs can occur at a rate of up to 1% and can be fatal. Myocarditis is the most prevalent of all cardiotoxicities. The purpose of this systematic review is to assess the seriousness of myocarditis, the most prevalent cardiotoxicity of ICIs, and the importance of screening. We chose studies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 criteria. Therefore, from 2018 to 2023, we gathered articles from databases such as PubMed, ScienceDirect, Web of Science, the Cochrane Library, and Google Scholar. Of the 665 studies identified based on various screening methods and quality assessment tools, 13 were selected for inclusion in the study. This study shows that although the risk of myocarditis in ICI therapy is low and the majority of cases are asymptomatic or mild, some cases can be deadly and disastrous, and physicians should be aware that if myocarditis is suspected based on clinical symptoms, troponin, electrocardiogram, and echocardiogram, treatment should be initiated accordingly.

Myasthenia gravis (MG) is one of the most common neuromuscular adverse effects of immune checkpoint inhibitors (ICIs) and can result in significant morbidity and mortality when it affects the bulbar and respiratory muscles. Diagnosing immune-related MG (irMG) is challenging due to its nonspecific presentation and high negativity rate for MG antibody markers. Patients, primary care providers, and emergency care providers should be educated about MG as a potential adverse effect of ICIs for timely diagnosis and intervention.