scholarly journals Fatal Cholestatic Liver Injury during Treatment with PD1 Immune Checkpoint Inhibitor for Malignant Melanoma: A Case Report

2020 ◽  
Vol 13 (2) ◽  
pp. 659-663 ◽  
Author(s):  
Thuridur Thorsteinsdottir ◽  
Teje Løitegård ◽  
Henrik Mikael Reims ◽  
Alina Carmen Porojnicu
Keyword(s):  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Liver Toxicity ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Treatment ◽  
Fatal Outcome ◽  
Metastatic Malignant Melanoma ◽  
Immune Mediated ◽  
The Cost ◽  
Cholestatic Liver Injury

The use of immune checkpoint inhibitors has dramatically improved the chance of surviving malignant melanomas; however, the effect comes at the cost of toxicities that are difficult to predict. Immune-mediated hepatitis is the most common form of liver toxicity, but fatal outcome is uncommon. We report the case of a 70-year-old female with metastatic malignant melanoma who developed severe liver toxicity characterized by bile duct injury and cholestasis. The condition progressed despite potent immunosuppressive treatment, plasmapheresis, and intensive supportive care; and the patient died while still having tumor response.

scholarly journals Bullous Pemphigoid Induced by Nivolumab in a Patient with Malignant Melanoma

2020 ◽  
Vol 4 (1) ◽  
pp. 7
Author(s):  
Eriko Adachi ◽  
Erina Yokoyama ◽  
Yuna Yamagami ◽  
Reiko Koga ◽  
Yoshiaki Yoshikawa
Keyword(s):  
Malignant Melanoma ◽  
Bullous Pemphigoid ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Serum Levels ◽  
Metastatic Malignant Melanoma ◽  
Clear Correlation ◽  
Cutaneous Toxicity ◽  
The Status

Immune checkpoint inhibitors, such as nivolumab, have been recognized that the enhanced immune responses often lead to immune-related adverse events (irAEs) in various organs. Although cutaneous toxicity is one of the most common irAEs, bullous pemphigoid (BP) with immune checkpoint inhibitors is rare. Herein, the authors report a case of BP in a patient of the metastatic malignant melanoma of the brain under the treatment of nivolumab. It is notable that this case showed the clear correlation between the status of using of nivolumab and serum levels of anti-BP180 antibody. In addition, the skin eruptions in the case were mainly pruritic erosive or crusted papules and these clinical features may be the clinical characteristics of BP induced by nivolumab.

A Case of Malignant Melanoma Associated with Polymyositis Treated with Immune Checkpoint Inhibitors

2019 ◽  
Vol 81 (5) ◽  
pp. 396-400 ◽  
Author(s):  
Hayato NOMURA ◽  
Osamu YAMASAKI ◽  
Tatsuya KAJI ◽  
Hiroshi WAKABAYASHI ◽  
Yoshia MIYAWAKI ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

scholarly journals Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

2017 ◽  
Vol 10 (1) ◽  
pp. 368-371 ◽  
Author(s):  
Keisuke Imafuku ◽  
Koji Yoshino ◽  
Kei Yamaguchi ◽  
Satoshi Tsuboi ◽  
Kuniaki Ohara ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Liver Function ◽  
Immune Checkpoint ◽  
Fulminant Hepatitis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Corticosteroid Treatment ◽  
Sudden Onset ◽  
Oral Corticosteroids

Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs). We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4). We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors.

scholarly journals HBV-related acute hepatitis due to immune checkpoint inhibitors in a patient with malignant melanoma

2017 ◽  
Vol 28 (12) ◽  
pp. 3103-3104 ◽  
Author(s):  
A.S. Koksal ◽  
B. Toka ◽  
A.T. Eminler ◽  
İ Hacibekiroglu ◽  
M.I. Uslan ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Acute Hepatitis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Liver toxicity in the era of immune checkpoint inhibitors: A practical approach

2018 ◽  
Vol 132 ◽  
pp. 125-129 ◽  
Author(s):  
Carmen Belli ◽  
Massimo Zuin ◽  
Luca Mazzarella ◽  
Dario Trapani ◽  
Paolo D’Amico ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Liver Toxicity ◽  
Checkpoint Inhibitors ◽  
Practical Approach

scholarly journals Multiple treatment comparison of seven new drugs for patients with advanced malignant melanoma: a systematic review and health economic decision model in a Norwegian setting

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e014880 ◽  
Author(s):  
Eva Pike ◽  
Vida Hamidi ◽  
Ingvil Saeterdal ◽  
Jan Odgaard-Jensen ◽  
Marianne Klemp
Keyword(s):  
Cost Effectiveness ◽  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cost Effective ◽  
Mek Inhibitor ◽  
New Drugs ◽  
Advanced Malignant Melanoma ◽  
Quality Adjusted Life

ObjectiveTo assess the relative effectiveness and cost-effectiveness of seven new drugs (cobimetinib, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib and vemurafenib) used for treatment of patients with advanced malignant melanoma in the Norwegian setting.DesignA multiple technology assessment.PatientsPatients with advanced malignant melanoma aged 18 or older.Data sourcesA systematic search for randomised controlled trials in relevant bibliographic databases.MethodsWe performed network meta-analyses using both direct and indirect evidence with dacarbazine as a common comparator. We ranked the different treatments in terms of their likelihood of leading to the best results for each endpoint. The cost-utility analysis was based on a probabilistic discrete-time Markov cohort model. The model calculated the costs and quality-adjusted life years (QALYs) with different treatment strategies from a healthcare perspective. Sensitivity analysis was performed by means of Monte Carlo simulation.ResultsMonotherapies with a programmed cell death 1 (PD-1) immune-checkpoint-inhibitor had a higher probability of good performance for overall survival than monotherapies with ipilimumab or BRAF/MEK inhibitors. The combination treatments had all similar levels of effectiveness to the PD-1 immune-checkpoint-inhibitors.PD-1 immune-checkpoint-inhibitors are more effective and more costly compared with ipilimumab in monotherapy. Nivolumab in combination with ipilimumab had higher costs and the same level of effectiveness as the PD-1 immune-checkpoint-inhibitors in monotherapy.BRAF/MEK inhibitor combinations (dabrafenib and trametinib or vemurafenib and cobimetinib) had both similar effectiveness and cost-effectiveness; however, the combination therapies are more likely to give higher quality adjusted life year gains than BRAF or MEK inhibitor monotherapies, but to a higher cost.ConclusionsNone of the drugs investigated can be considered cost-effective at what has normally been considered a reasonable willingness-to-pay (WTP) in Norway. Price reductions (from the official list prices) in the region of 63%–84% would be necessary for these drugs to be cost-effective at a WTP of €55 850 per QALY.

scholarly journals When steroids are not enough in immune-related hepatitis: current clinical challenges discussed on the basis of a case report

2020 ◽  
Vol 8 (2) ◽  
pp. e001322 ◽  
Author(s):  
Dimitrios C Ziogas ◽  
Aikaterini Gkoufa ◽  
Evangelos Cholongitas ◽  
Panagiotis Diamantopoulos ◽  
Amalia Anastasopoulou ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Liver Toxicity ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Phase Iii ◽  
Steroid Resistant ◽  
Immune Mediated ◽  
Cancer Types ◽  
Clinical Considerations ◽  
Steroid Refractory

Unleashing adaptive immunity via immune checkpoint inhibitors (ICPIs) in many cancer types led to durable antitumor responses and prolonged survivals and also added some new immune-related adverse events (irAEs) to the ‘old-fashioned’ safety profile of chemotherapy. Among bowel and endocrine irAEs, immune-mediated hepatotoxicity/hepatitis is a less common and far less well-studied toxicity, which, however, could develop into a serious complication, especially when it becomes persistent or refractory to steroids. Its incidence, onset and severity vary widely, depending on the type of underlying treated cancer, the class, the dosage and the duration of immunotherapy as well as the way of its administration (as a single agent or in combination with other ICPI or chemotherapy). In this study, we present a patient with metastatic melanoma who developed severe steroid-resistant ir-hepatitis after treatment with ipilimumab and required triple concurrent immunosuppression with prednisolone, mycofenolate mofetil and tacrolimus in order for his liver toxicity to be resolved. Intrigued by this case, we focused further on melanoma, as the disease-paradigm of immunotherapy in cancer, reviewed the reported incidence of hepatotoxicity among phase III ICPIs-containing trials on melanoma and discussed the main clinical considerations regarding the diagnosis and the management of persistent/steroid-refractory ir-hepatitis. As more clinical experience is gradually gained on this challenging topic, better answers are provided to questions about the appropriate diagnostic workup, the necessity of liver biopsy, the available immunosuppressive options beyond corticosteroids (their combinations and/or their sequence) as well as the correct decision on withdrawing or resuming immunotherapy. Nonetheless, a thorough multidisciplinary discussion is still required to individualize the overall approach in each case after failure of steroids.

scholarly journals Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217260
Author(s):  
Tommaso Morelli ◽  
Kohei Fujita ◽  
Gil Redelman-Sidi ◽  
Paul T Elkington
Keyword(s):  
Immune Response ◽  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Treatment ◽  
Common Side Effect ◽  
Inflammatory Immune Response ◽  
New Framework

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.

scholarly journals Challenge of immune-mediated adverse reactions in the emergency department

2019 ◽  
Vol 36 (6) ◽  
pp. 369-377 ◽  
Author(s):  
Gregory A Daniels ◽  
Angela D Guerrera ◽  
Donna Katz ◽  
Jayne Viets-Upchurch
Keyword(s):  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
High Dose ◽  
Clear Understanding ◽  
Immune Mediated ◽  
Multiple Drugs

Multiple drugs of a new class of cancer treatments called immune checkpoint inhibitors, which work by enabling the immune system to attack tumour cells, have been approved for a variety of indications in recent years. Immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 and programmed death-1, are part of the normal immune system and regulate immune activation. Treatment with inhibitors of these checkpoints can significantly improve response rates, progression-free survival and overall survival of patients with cancer; it can also result in adverse reactions that present similarly to other conditions. These immune-mediated adverse reactions (IMARs) are most commonly gastrointestinal, respiratory, endocrine or dermatologic. Although patients’ presentations may appear similar to other types of cancer therapy, the underlying causes, and consequently their management, may differ. Prompt recognition is critical because, with appropriate management, most IMARs resolve and patients can continue receiving immune checkpoint inhibitor treatment. Rarely, these IMARs may be life-threatening and escape detection from the usual evaluations in the emergency environment. Given the unusual spectrum and mechanism of IMARs arising from immune checkpoint inhibitors, emergency departmentED staff require a clear understanding of the evaluation of IMARs to enable them to appropriately assess and treat these patients. Treatment of IMARs, most often with high-dose steroids, differs from chemotherapy-related adverse events and when possible should be coordinated with the treating oncologist. This review summarises the ED presentation and management of IMARs arising from immune checkpoint inhibitors and includes recommendations for tools and resources for ED healthcare professionals.

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