Malignant melanoma followed by the development of type I diabetes and thyroid dysfunction caused by immune checkpoint inhibitors : Two case reports

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.

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

Annals of Oncology ◽

10.1093/annonc/mdx502 ◽

2017 ◽

Vol 28 (12) ◽

pp. 3103-3104 ◽

Cited By ~ 21

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

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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 ◽

10.1136/bmjopen-2016-014880 ◽

2017 ◽

Vol 7 (8) ◽

pp. e014880 ◽

Cited By ~ 7

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.

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Thyroid dysfunction and survival in cancer patients treated with immune checkpoint inhibitors: analyses from a large single tertiary cancer center database

Acta Oncologica ◽

10.1080/0284186x.2021.1958006 ◽

2021 ◽

pp. 1-6

Author(s):

Ruth Percik ◽

Yair Liel ◽

Damien Urban ◽

Jair Bar ◽

Eytan Ben-Ami ◽

...

Keyword(s):

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Thyroid Dysfunction ◽

Checkpoint Inhibitors ◽

Cancer Center ◽

Tertiary Cancer Center

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Successful Treatment of a Patient with anti-PD1 Antibody-Resistant Advanced Mucosal Melanoma with Nivolumab, Ipilimumab plus Denosumab Combination Therapy

Case Reports in Oncology ◽

10.1159/000506327 ◽

2020 ◽

Vol 13 (1) ◽

pp. 271-275 ◽

Cited By ~ 1

Author(s):

Taku Fujimura ◽

Yumi Kambayashi ◽

Kentaro Ohuchi ◽

Ryo Amagai ◽

Yota Sato ◽

...

Keyword(s):

Malignant Melanoma ◽

Combination Therapy ◽

Nasal Cavity ◽

Immune Checkpoint ◽

Cutaneous Melanoma ◽

Japanese Population ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Mucosal Melanoma ◽

Mutation Burden

Since the incidence of mucosal melanoma is higher in the Japanese population compared to Caucasians, and since mucosal melanoma possesses a lower mutation burden compared to cutaneous melanoma, the efficacy of anti-PD1 antibody (Ab) monotherapy for mucosal melanoma is limited. Therefore, other targeting molecules that enhance the anti-tumor effects of immune checkpoint inhibitors are needed. In this report, we present a case with anti-PD1 Ab-resistant recurrent malignant melanoma of the nasal cavity successfully treated with nivolumab, ipilimumab plus denosumab combination therapy.

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Concealed complete response in melanoma patients under therapy with immune checkpoint inhibitors: two case reports

Journal for ImmunoTherapy of Cancer ◽

10.1186/s40425-017-0309-3 ◽

2018 ◽

Vol 6 (1) ◽

Cited By ~ 6

Author(s):

Stefan Schliep ◽

Abbas Agaimy ◽

Alexander Cavallaro ◽

Franklin Kiesewetter ◽

Gerold Schuler ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Case Reports ◽

Complete Response ◽

Melanoma Patients

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Tumor Suppressor Immune Gene Therapy to Reverse Immunotherapy Resistance

10.1101/2020.12.27.20248913 ◽

2021 ◽

Author(s):

Sunil Chada ◽

Dora Wiederhold ◽

Kerstin B. Menander ◽

Beatha Sellman ◽

Max Talbott ◽

...

Keyword(s):

Gene Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Type I ◽

Immune Gene ◽

Gene Signatures ◽

Complete Tumor

AbstractBackgroundWhile immune checkpoint inhibitors are becoming a standard of care for multiple types of cancer, the majority of patients do not respond to this form of immunotherapy. New approaches are required overcome resistance to immunotherapies.MethodsWe investigated the effects of adenoviral p53 (Ad-p53) gene therapy in combination with immune checkpoint inhibitors and selective IL2 or IL15 CD122/132 agonists in the aggressive B16F10 tumor model resistant to immunotherapies. To assess potential mechanisms action, pre and post Ad-p53 treatment biopsies were evaluated for changes in gene expression profiles by Nanostring IO 360 assays.ResultsSubstantial synergy of “triplet” Ad-p53 + CD122/132 + anti-PD-1 therapy resulted in potential curative effects associated with complete tumor remissions of both primary and contralateral tumors. Interestingly, contralateral tumors which were not injected with Ad-p53 showed robust abscopal effects resulting in statistically significant decreases in tumor size and increased survival (p<0.001). None of the monotherapies or doublet treatments induced complete tumor regressions. Ad-p53 treatment increased Type I Interferon, CD8+ T cell, immuno-proteosome antigen presentation and tumor inflammation gene signatures. Ad-p53 treatment also decreased immune suppressive TGF-beta, beta-catenin, macrophage, and endothelium gene signatures, which may contribute to enhanced immune checkpoint inhibitor (CPI) efficacy. Unexpectedly, a number of previously unidentified, strongly p53 down regulated genes associated with stromal pathways and IL10 expression identified novel anti-cancer therapeutic applications.ConclusionsThese results imply the ability of Ad-p53 to induce efficacious local and systemic anti-tumor immune responses with the potential to reverse resistance to immune checkpoint inhibitor therapy when combined with CD122/132 agonists and immune checkpoint blockade. Our findings further imply that Ad-p53 has multiple complimentary immune mechanisms of action which support future clinical evaluation of triplet Ad-p53, CD122/132 agonist and immune checkpoint inhibitor combination treatment.

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Clinical practice alert on the use of immune checkpoint inhibitors in patients latently infected with tuberculosis

10.35543/osf.io/678kt ◽

2019 ◽

Author(s):

Chirag Dhar

Keyword(s):

Clinical Practice ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Case Reports ◽

Latent Tuberculosis ◽

Latently Infected ◽

Multiple Case

Multiple case reports have been published on the risk of tuberculosis activation in patients on immune checkpoint inhibitors (ICPIs). To this matter, I caution clinicians to test for latent tuberculosis before starting their patients on ICPIs.

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