• 대한한방내과학회지
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• 제42권4호
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• pp.590-604
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• 2021

Objectives: The purpose of this study is to examine the safety of Korean medicine treatment in patients vaccinated with the AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19/AZD1222). Methods: We investigated patients at Kyung Hee University Korean Medicine Hospital who were vaccinated with the AstraZeneca COVID-19 vaccine between June 1, 2021 and June 30, 2021. The safety of Korean medicine treatment was evaluated by examining adverse events that occurred within seven days of vaccination, including liver function and kidney function testing, assessment of the severity of adverse events, and examination of causality to vaccines and Korean medicine treatment. Results: Eleven patients vaccinated with the first dose of the AstraZeneca COVID-19 vaccine were included. A total of 19 adverse events were reported: 15 systemic adverse events, three local adverse events, and one alanine aminotransferase increase. The most commonly reported systemic adverse events were fatigue (4 cases, 36.4%), headache (4 cases, 36.4%), and myalgia (4 cases, 36.4%). All adverse events were rated below moderate (grade 2) in severity. Systemic and local adverse events were evaluated as definitely related to vaccination and unlikely to be related to Korean medicine treatment, while alanine aminotransferase increase was evaluated as unlikely to be related to either the vaccine or Korean medicine treatment. Aspartate transaminase, Blood urea nitrogen, and creatinine were measured within the reference range after vaccination. Conclusion: Our results suggest that the severity and frequency of adverse events in patients vaccinated with the AstraZeneca COVID-19 vaccine did not increase after Korean medicine treatment.

• IMMUNE NETWORK
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• 제20권1호
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• pp.9.1-9.21
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• 2020

Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.

• Journal of Yeungnam Medical Science
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• 제38권4호
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• pp.366-370
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• 2021

Immune checkpoint inhibitors (ICIs) have become the main drugs for programmed cell death receptor-1 or ligand-1 expressing non-small cell lung cancer (NSCLC) combined with conventional chemotherapy. ICIs are generally more tolerable than cytotoxic chemotherapies in terms of toxicity, and ICI-related adverse events are mild and manageable. However, these drugs may lead to unexpected severe adverse events such as immune-related hematologic toxicities, which could be life-threatening. Here, a rare case of a pembrolizumab-related adverse event in a patient with NSCLC who showed early-onset hemolytic anemia and recovered by high-dose steroid and a series of plasma exchanges is reported.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.10.1-10.11
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• 2018

Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.

• 한국임상약학회지
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• 제31권3호
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• pp.188-197
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• 2021

Objective: PD-1 inhibitors have demonstrated improved health outcomes in cancer patients. PD-1 inhibitors are well-tolerated and associated with immune-related adverse events. The objectives of this study are to analyze use patterns of PD-1 inhibitors in patients with cancer and to investigate the incidence of thyroid-related adverse reactions in patients treated with PD-1 inhibitors. Methods: The study included patients who had been administered PD-1 inhibitors (either nivolumab or pembrolizumab) at the Samsung Medical Center between October 1, 2016 and June 30, 2017. Data was collected from electronic medical records and tested using Mann-Whitney tests and Chi-Square tests for statistical significance. Associations between PD-1 inhibitors and incidence of adverse events were tested using Cox regression for age, gender, BMI, ECOG PS and medication. Results: Two hundred fifteen patients were identified as eligible for analyses. Thyroid-related adverse events occurred in 20% of patients (n=43). Thyroid function tests (TFTs) was performed in 109 patients (50.7%). Positive results of PD-L1 testing were found in 53.2% of the 94 patients who had the test. Approved doses of nivolumab (3 m/kg) and pembrolizumab (200 mg) were administered in 70.4% and 53% of patients, respectively. The analysis of risk factor of thyroid-related adverse reaction did not show statistically significant differences (Cox regression). Conclusion: Thyroid-related adverse events are common in patients treated with PD-1 inhibitors and hypothyroidism is the most frequent adverse reaction. Routine TFTs monitoring is strongly recommended to evaluate thyroid function in real-world clinical practice.

• IMMUNE NETWORK
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• 제20권1호
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• pp.8.1-8.15
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• 2020

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

• Korean Journal of Radiology
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• 제22권8호
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• pp.1310-1322
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• 2021

Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.

• International journal of thyroidology
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• 제11권2호
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• pp.172-175
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• 2018

Anti-programmed cell death-1 (PD-1) humanized monoclonal antibody inhibits PD-1 activity by binding to the PD-1 receptor on T-cells and blocking PD-1 ligands and induces immune tolerance of cancer cells. It has been widely used for various kinds of cancer treatment. However, many immune-related adverse events (irAEs) have been reported because it modulates our immune system. In this case study, we reported a case of 42-year-old woman with Hashimoto's thyroiditis who showed rapid aggravation of thyroid goiter and acute hyperventilation syndrome after treatment with PD-1 inhibitor as a neoadjuvant chemotherapy for breast cancer.

• 대한신경과학회지
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• 제36권4호
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• pp.329-332
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• 2018

Immune checkpoint inhibitor is associated with variety of immune-related adverse events. We present a case of polyneuropathy induced by immune checkpoint inhibitor, which was refractory to steroid and immunoglobulin. While high-dose steroid and immunoglobulin were not effective, we tried rituximab which is effective in other immune-mediated polyneuropathy. After rituximab treatment, patient's clinical symptom and nerve conduction study finding was markedly improved. We suggest rituximab might be effective in polyneuropathy induced by immune checkpoint inhibitor.

• Journal of Yeungnam Medical Science
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• 제39권1호
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• pp.62-66
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• 2022

Immune checkpoint inhibitor (ICI)-associated adrenal insufficiency is rare but may become a serious adverse event in patients treated with ICIs. The present case report documents two cases of adrenal insufficiency developed during chemotherapy plus tislelizumab (百泽安, Baize'an; BeiGene Ltd.) therapy in patients with advanced gastric cancer. Adrenal insufficiency developed after 6 and 13 cycles of treatment and was well controlled with hydrocortisone. The patients also developed hypothyroidism, which was managed with levothyroxine. Two patients showed a partial response, and one patient out of two achieved a near-complete response, sustaining over 11 months. Increased awareness of ICI-related adrenal insufficiency is crucial for early detection and prompt management of patients treated with ICIs.