Adverse Effects Of Immune Checkpoint Inhibitors Research Articles

A Potential Pneumothorax Induced by Immune Checkpoint Inhibitors: A Case Report and Literature Review

Background and Objectives: Immune checkpoint inhibitors (ICIs), which target immune checkpoints in cancer cells, are increasingly used as a mainstay in anticancer treatment. The combination of atezolizumab and bevacizumab is also a first-line treatment for hepatocellular carcinoma (HCC). However, ICIs can cause immune-related adverse events (IrAEs) which range from mild to severe, potentially leading to the need for discontinuing immunotherapy. We report a case of a pneumothorax, a rare side effect caused by IrAEs. Materials and Methods: This paper reports a case of a 78-year-old male HCC patient who developed a recurrent pneumothorax, suspected to be an adverse effect of ICIs. Results: The patient was a current smoker with a 30 pack-year smoking history. Prior to initiating ICIs, a chest CT scan showed mild emphysema and fibrosis attributable to smoking. Following ICI treatment, the patient developed a recurrent pneumothorax. Further tests revealed no underlying cause for the pneumothorax other than the ICIs and smoking, and there were no signs of intrapulmonary metastasis or pneumonitis. Conclusions: When a pneumothorax occurs in a patient undergoing immunotherapy, it is important to consider it as a potential adverse effect of the treatment. Special attention should be given to the possibility that immunotherapy may exacerbate underlying lung conditions. Patients should be advised on the importance of smoking cessation. As there are currently no guidelines for resuming immunotherapy after a pneumothorax, it is crucial to weigh the risks and benefits and consider dose reduction or discontinuation of the medication.

Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors: Where do we stand?

Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) is limited by factors such as tumor size, number, portal venous or hepatic venous invasion and extrahepatic disease. Although previously established criteria, such as Milan or UCSF, have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes, there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation. Immune checkpoint inhibitors (ICI) such as atezolizumab, pembrolizumab, or nivolumab have given hope to this group of patients. We completed a comprehensive literature review using PubMed, Google Scholar, reference citation analysis, and CrossRef. The search utilized keywords such as 'liver transplant', 'HCC', 'hepatocellular carcinoma', 'immune checkpoint inhibitors', 'ICI', 'atezolizumab', and 'nivolumab'. Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT, with acceptable early outcomes comparable to other criteria. Adverse effects of ICI have also been reported during the perioperative period. In such cases, a 1.5-month interval between ICI therapy and LT has been suggested. Overall, the results of downstaging using combination immunotherapy were encouraging and promising. Early reports suggested a potential ray of hope for patients with CLD and advanced HCC, especially those with multifocal HCC or branch portal venous tumor thrombosis. However, prospective studies and further experience will reveal the optimal dosage, duration, and timing prior to LT and evaluate both short- and long-term outcomes in terms of rejection, infection, recurrence rates, and survival.

Adverse Effects of Immune-Checkpoint Inhibitors: A Comprehensive Imaging-Oriented Review

Immune-checkpoint inhibitors (ICIs) are immunomodulatory monoclonal antibodies, which increase antitumor immunity of the host and facilitate T-cell-mediated actions against tumors. These medications have been used in recent years as a weapon against advanced stage malignancies, such as melanoma, renal cell carcinoma, lymphoma, small or non-small cell lung cancer, and colorectal cancer. Unfortunately, they are not free from possible adverse effects (immune-related adverse events-irAEs) that mainly affect skin, gastrointestinal, hepatic, and endocrine systems. Early diagnosis of irAEs is essential to correctly and rapidly manage patients, with ICIs suspension and therapies administration. Deep knowledge of the imaging and clinical patterns of irAEs is the key to promptly rule out other diagnoses. Here, we performed a review of the radiological signs and differential diagnosis, based on the organ involved. The aim of this review is to provide guidance to recognize the most significant radiological findings of the main irAEs, based on incidence, severity, and the role of imaging.

Abstract 12770: Immune Checkpoint Inhibitor Induced Myocarditis: An Interesting Case of Reversible Complete Heart Block

BACKGROUND: Immune checkpoint inhibitors (ICI) have changed the treatment scope for malignancies. The mechanism of ICIs is targeting of immune checkpoints that can suppress a response to a stimulus which can effect any organ. Adverse effects are usually mild but myocarditis, although rare, is becoming more recognized as a life threatening entity. The increase in mortality seen with ICI-induced myocarditis is more frequent with combination therapy. Most cases of ICI-induced myocarditis are limited to direct myocardial injury but there is a lack of evidence regarding conduction disease. CASE DESCRIPTION: We present a 74-year-old man with known metastatic malignancy recently started on ICI with ipilimumab and nivolumab who presented with complaints of abdominal pain, SOB and chest pain. His ED workup was consistent with colitis and acute PE without RV strain. Troponins and BNP were elevated and his ECG showed 3rd degree AV block. A coronary angiogram was negative for obstructive CAD and a temporary trans-venous pacemaker was placed. Cardiac MR showed LGE with active inflammation of the mid-myocardium. The patient had complex presentation as a side effect of ICI leading to myocarditis, 3rd degree AV block, colitis and PE. He was started on high dose methylprednisolone 1gm daily. Within 24 hours there was improvement evidenced by intermittent return of intrinsic conduction. At 48 hours there was marked improvement with restoration of sinus rhythm without evidence of AV block and/or use of the temporary pacemaker. Discussion: Early recognition of disease processes is difficult when there is minimal data to support a cause and effect. Increasing clinical awareness regarding adverse effects of ICI is paramount in decreasing the risk for unnecessary therapies, in our case, placement of a permanent pacemaker. Although there have been case reports of ICI-induced myocarditis, there has not been expert consensus regarding management of conduction pathway abnormalities.

MO221ONLY A SIMPLE CASE OF AKI IN AN ONCOLOGIC PATIENT?

Abstract Background Nivolumab is a drug belonging to the class of Immune Checkpoint Inhibitors (ICPI), the use of which has improved the prognosis for patients with various advanced malignancies. These agents are associated with several "immune-mediated" adverse effects, although the literature on Nivolumab renal toxicity is poor and anecdotal. A rare immune-mediated renal adverse event is acute interstitial nephritis (AIN) that often imposes Nivolumab suspension. Case report We present the case of a 75-year-old woman with stage IV melanoma (inguinal and external iliac lymph node metastases without localization of the primitive lesion). At diagnosis, renal function was normal by age (Creatinine 0.89 mg/dl; CKD EPI eGFR 71 ml/min/1.73 m2). After lymphadenectomy, an adjuvant treatment with Nivolumab was initiated. At 4-month follow-up, the patient was hospitalized for AKI (creatinine 2.6 mg/dl; eGFR 17,3 ml/min/1.73 m2). Although, renal function decline was not accompanied by signs of systemic immunoactivation, Nivolumab was suspended. In the following weeks, only a partial renal function recovery was observed, still limiting immunotherapy reintroduction. Thus, the patient was referred to our Onconephrology Outpatient Unit for a multidisciplinary approach. We performed a urinalysis with microscopy study of the sediment and observed rare dysmorphic red blood cells and leukocytes. To exclude a glomerulopathy, a comprehensive screening for autoimmune diseases and 24 hours proteinuria were also measured and found not significant (Table 1). Renal ultrasound did not show any relevant alteration. Based on our original suspicion of AIN, although in absence of an history of fever, rush or eosinophilia, we introduced Prednisone 25 mg/day. In the following weeks, blood and urine tests showed a significant improvement in renal function (serum creatinine 1.06 mg/dL, eGFR CKD-EPI 51 mL/min/1.73m2) and the absence of red blood cells, leukocytes and proteinuria in the urinalysis. Based on nephrologist advice, the patient was then able to resume the cancer treatment with a maintenance dose of prednisone equal to 5 mg/day. Conclusion AIN is a rare adverse effect of ICPIs that mandates the close monitoring of renal function in patients under immunotherapy with these agents. AKI occurrence in patients treated with ICPIs should always lead to investigate a possible AIN, even in the absence of the classic symptom set of fever, rush and eosinophilia and with minimal changes in urinalysis. Based on our single observation, and after an accurate literature review, we suggest the initiation of a corticosteroid treatment in oncologic patients on an ICPI complicated with AKI and with suspicion of AIN at urinalysis. Moreover, this case report thickens the importance of a multidisciplinary approach to oncologic patients not only when a conventional nephrotoxic chemotherapy has to be started, but also in case of ICIPs use. The nephrologist advice, in fact, could be useful in both preventing and treating severe renal complications such as AIN, also allowing the oncologic therapy maintenance.

Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma.

Immune-modulatory therapy, especially with immune-checkpoint inhibitors (ICIs), has reshaped cancer therapeutics. Immunotherapy is relatively a novel approach that can effectively delay the progression of aggressive tumors and inhibit tumor recurrence and metastasis in many different tumor types. In the past years, ICIs have shown a sustained response and promising long-term survival in patients with advanced hepatocellular carcinoma (HCC). Nevertheless, ICI therapy can unbalance the immune system and result in a wide range of immune-related adverse events (irAEs), which are generally manageable but occasionally lead to a fatal outcome. HCC generally develops in the context of liver cirrhosis which is typically caused by viral hepatitis and non-alcoholic steatohepatitis. These underlying diseases may cause symptoms that overlap with irAEs and lead to consequences such as late recognition, inadequate work-up, and inappropriate treatment. Owing to the growing use of immunotherapy in HCC, it is necessary for clinicians to strengthen their understanding of the frequency, clinical features, and management of irAEs. This review focuses on the common toxicities associated with ICI therapy in patients with HCC and summarizes therapeutic strategies that can be used to monitor and manage such toxicities.

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers.

Gynecologic cancers account for approximately 11% of the newly diagnosed cancers in women in the United States and for 18% globally. The presence of tumor-infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICIs), including anti programmed cell death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), which have been approved for treating different types of malignancies. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host–tumor interaction. There are several the US food and drug administration (FDA)-approved ICIs targeting PD-1, including pembrolizumab and nivolumab, as well as those targeting PD-L1, including avelumab, atezolizumab, and durvalumab for melanoma, renal cell cancer, colorectal cancer, head and neck cancer, cervix cancer, urothelial cancer, and lung cancer. Current pre-clinical and clinical studies assessing PD-1/PD-L1 inhibitors in several gynecologic cancers have reported significant antitumor activity. In this review, we investigate pre-clinical and clinical studies that describe the safety and efficacy of anti-PD-1/PD-L1 antibodies, with a particular focus on ongoing clinical trials, analyzing the oncological outcome and adverse effects of ICIs in gynecologic cancers.

Clinical diagnosis and treatment of immune checkpoint inhibitor-associated adverse events in the digestive system.

Immunotherapy for malignant tumors is a hot spot in current research and the treatment of cancer. The activation of programmed cell death receptor‐1 (PD‐1) and cytotoxic T lymphocyte‐associated antigen 4 (CTLA)‐4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune‐checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune‐related adverse events (irAEs). The digestive system, including the gastrointestinal tract and liver which are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune‐related organs, is the most commonly affected system of irAEs. This review explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.

Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease

The widespread clinical use of immune checkpoint inhibitors (ICI) has increased our knowledge on their adverse effects on chronic inflammatory diseases. Atherosclerosis, a low-grade lipid-driven inflammatory disease of the larger...

Clinical Diagnosis and Treatment of Immune-related Adverse Events in Digestive System Related to Immune Checkpoint Inhibitors

恶性肿瘤的免疫治疗是当前肿瘤研究和治疗领域的热点，免疫检查点分子程序性死亡受体-1（programmed cell death receptor-1, PD-1）和细胞毒性T淋巴细胞相关抗原4（cytotoxic T lymphocyte-associated antigen 4, CTLA-4）相关信号通路的激活可以抑制T淋巴细胞活化，肿瘤细胞通过激活该信号通路实现免疫逃逸。免疫检查点抑制剂（immuno-checkpoint inhibitors, ICIs）通过抑制该信号通路，活化T淋巴细胞发挥机体对肿瘤细胞的清除。因此，ICIs的相关毒性包括免疫相关的不良事件（immune-related adverse effects, irAEs）。消化系统如胃肠道、肝脏作为人体重要的消化吸收器官、代谢解毒器官，同时也是重要的免疫相关器官，是irAEs的常见受累系统。本文将分别对ICIs的肝脏、胃肠道不良反应的发生率、临床表现、诊断和处理分别进行阐述。

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.