scholarly journals Temporal observation of endoscopic and histological findings of gastritis after administration of an immune checkpoint inhibitor: a case report

2022 ◽  
Author(s):  
Keita Saito ◽  
Daiki Ozono ◽  
Hironobu Nagumo ◽  
Masayo Yoshimura ◽  
Yoko Masuzawa
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Epigastric Pain ◽  
Lymphocytic Infiltration ◽  
The Body ◽  
Gastric Antrum ◽  
Upper Gastrointestinal Endoscopy ◽  
Drug Induced ◽  
Old Japanese ◽  
Greater Curvature

AbstractA 71-year-old Japanese man was treated with 200 mg of pembrolizumab for lung adenocarcinoma with multiple bone metastases at the Department of Respiratory Medicine of Kameda General Hospital. After 19 treatment courses, he complained of epigastric pain before meals. Upper gastrointestinal endoscopy showed multiple erosions in the gastric antrum, and antacids were administered at follow-up. After 27 treatment courses, the patient underwent another endoscopy because of anorexia. The erosions were enlarged and had increased from the gastric antrum to the greater curvature of the body. Histological biopsy showed lymphocytic infiltration with a predominance of CD8-positive T cells. The patient had previously been treated for Helicobacter pylori infection, and we suspected drug-induced gastritis due to the administration of immune checkpoint inhibitors in the course of the disease. Pembrolizumab was discontinued, and the patient’s symptoms gradually improved. Endoscopic examinations were performed 2, 5, and 9 months after discontinuation of pembrolizumab, and improvement in mucosal findings and decreased lymphocyte infiltration were confirmed each time. The patient has remained without any relapse of symptoms for more than 1 year after discontinuing treatment.

scholarly journals Immune checkpoint inhibitor induced autoimmune encephalitis in a patient with metastatic melanoma

2020 ◽  
Vol 7 (3) ◽  
pp. 1
Author(s):  
Nivedita Sudhekar ◽  
Binoy Yohannan ◽  
Mark Feldman
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Combined Therapy ◽  
Autoimmune Encephalitis ◽  
The Body

Background: Immune checkpoint inhibitors have changed the therapeutic milieu for patients with metastatic melanoma. However, their use may promote autoimmunity in virtually any organ in the body due to the blockade of intrinsic immune down regulators such as cytotoxic T-lymphocyte antigen- 4 (CTLA-4), programmed cell death 1 (PD1) or its ligand (PDL1). Immune mediated adverse neurological events are rare with these agents, however, and are seen in < 1% of treated patients. We report a patient with immune checkpoint inhibitor associated autoimmune encephalitis, with complete clinical recovery after treatment.Case Report: A 49-year-old female with metastatic melanoma currently on nivolumab therapy but recently on ipilimumab/nivolumab combined therapy presented with a new headache. She also reported associated confusion, loss of balance, personality changes and language difficulty. Magnetic resonance imaging of the brain did not reveal any evidence of metastasis, infarct, meningitis, or encephalitis. Lumbar puncture revealed an elevated protein level and pleocytosis, with a normal glucose level. She was started on empiric glucocorticoid therapy with a presumptive diagnosis of immune checkpoint inhibitor associated autoimmune encephalitis. She improved considerably by day 3 of treatment with complete resolution of neurological symptoms by day 5.Conclusion: Immune checkpoint inhibitors are increasingly important in cancer immunotherapy as they can cause sustained remissions in patients with metastatic melanoma and other malignancies. Because these drugs block immune-regulatory targets, they can lead to enhanced activation of immune system resulting in immune-related adverse events. Autoimmune encephalitis is a rare immune-related adverse event associated with immune checkpoint inhibitors. The incidence of autoimmune encephalitis is higher with combination or sequential CTLA-4 (ipilimumab) and PD1(nivolumab) inhibitor therapy than with monotherapy. With more widespread use of immunotherapy, it is important for clinicians to be aware of this rare and reversible cause of encephalitis. Early recognition and prompt initiation of immunosuppressive therapy with glucocorticoids is essential to enhance neurological recovery.

Evolving spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors results from the WHO's pharmacovigilance database

2020 ◽  
Vol 111 ◽  
pp. 102454 ◽  
Author(s):  
Céline Anquetil ◽  
Joe-Elie Salem ◽  
Bénédicte Lebrun-Vignes ◽  
Sara Touhami ◽  
Anne-Claire Desbois ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Drug Induced ◽  
Pharmacovigilance Database

scholarly journals Case Report: A Case of Trimethoprim/Sulfamethoxazole-Triggered Hypotensive Shock: Cytokine Release Syndrome Related to Immune Checkpoint Inhibitors and Drug-Induced Hypersensitivity Syndrome

2021 ◽  
Vol 11 ◽  
Author(s):  
Tetsuya Urasaki ◽  
Makiko Ono ◽  
Toshiaki Mochizuki ◽  
Koichi Takeda ◽  
Aya Nishizawa ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Interstitial Pneumonitis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hypersensitivity Syndrome ◽  
High Dose ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Drug Induced ◽  
Prophylactic Administration

Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

scholarly journals Introduction to the Theme “Old and New Toxicology: Interfaces with Pharmacology”

2021 ◽  
Vol 61 (1) ◽  
pp. 1-7
Author(s):  
Max Costa ◽  
Terrence F. Blaschke ◽  
Susan G. Amara ◽  
Urs A. Meyer ◽  
Paul A. Insel
Keyword(s):  
Checkpoint Inhibitors ◽  
Vascular Inflammation ◽  
Cholinergic Receptor ◽  
Cardiovascular Complications ◽  
The Body ◽  
Drug Induced ◽  
Nicotinic Cholinergic Receptor ◽  
Pharmacology And Toxicology ◽  
Sites Of Action ◽  
Multicellular Organisms

The theme of Volume 61 is “Old and New Toxicology: Interfaces with Pharmacology.” Old toxicology is exemplified by the authors of the autobiographical articles: B.M. Olivera's work on toxins and venoms from cone snails and P. Taylor's studies of acetylcholinesterase and the nicotinic cholinergic receptor, which serve as sites of action for numerous pesticides and venoms. Other articles in this volume focus on new understanding and new types of toxicology, including ( a) arsenic toxicity, which is an ancient poison that, through evolution, has caused most multicellular organisms to express an active arsenic methyltransferase to methylate arsenite, which accelerates the excretion of arsenic from the body; ( b) small molecules that react with lipid dicarbonyls, which are now considered the most toxic oxidative stress end products; ( c) immune checkpoint inhibitors (ICIs), which have revolutionized cancer therapy but have numerous immune-related adverse events, including cardiovascular complications; ( d) autoimmunity caused by the environment; ( e) idiosyncratic drug-induced liver disease, which together with the toxicity of ICIs represents new toxicology interfacing with pharmacology; and ( f) sex differences in the development of cardiovascular disease, with men more susceptible than women to vascular inflammation that initiates and perpetuates disease. These articles and others in Volume 61 reflect the interface and close integration of pharmacology and toxicology that began long ago but continues today.

scholarly journals Immune checkpoint inhibitor-associated gastrointestinal and hepatic adverse events and their management

2019 ◽  
Vol 12 ◽  
pp. 175628481988419 ◽  
Author(s):  
Uday N. Shivaji ◽  
Louisa Jeffery ◽  
Xianyong Gui ◽  
Samuel C. L. Smith ◽  
Omer F. Ahmad ◽  
...  
Keyword(s):  
Early Intervention ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Management Strategies ◽  
Intestinal Barrier ◽  
Common Side Effect ◽  
Drug Induced ◽  
Immune Balance ◽  
Steroid Refractory

Background: Drug-induced colitis is a known complication of therapies that alter the immune balance, damage the intestinal barrier or disturb intestinal microbiota. Immune checkpoint inhibitors (ICI) directed against cancer cells may result in activated T lymphocyte-induced immune-related adverse events (AEs), including immune-related colitis and hepatitis. The aim of this review article is to summarize the incidence of gastrointestinal (GI) and hepatic AEs related to ICI therapy. We have also looked at the pathogenesis of immune-mediated AEs and propose management strategies based on current available evidence. Methods: A literature search using PubMed and Medline databases was undertaken using relevant search terms pertaining to names of individual drugs, mechanism of action, related AEs and their management. Results: ICI-related GI AEs are common, and colitis appears to be the most common side effect, with some studies reporting incidence as high as 30%. The incidence of both all-grade colitis and hepatitis were highest with combination therapy with anti-CTLA-4/PD-1; severity of colitis was dose-dependent (anti-CTLA-4). Early intervention is associated with better outcomes. Conclusion: ICI-related GI and hepatic AEs are common and clinicians need to be aware. Patients with GI AEs benefit from early diagnosis using endoscopy and computed tomography. Early intervention with oral steroids is effective in the majority of patients, and in steroid-refractory colitis infliximab and vedolizumab have been reported to be useful; mycophenolate has been used for steroid-refractory hepatitis.

Liver injury by immune checkpoint inhibitors in patients with hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 341-341 ◽  
Author(s):  
Nicola Personeni ◽  
Tiziana Pressiani ◽  
Antonio Capogreco ◽  
Arianna Dal Buono ◽  
Antonio D'Alessio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Subsequent Treatment ◽  
Drug Induced ◽  
Increased Risk ◽  
Grade 3

341 Background: In patients with hepatocellular carcinoma (HCC) and baseline liver dysfunction, hepatic immune-related adverse events (HIRAEs) during immunotherapy have not been adequately characterized and their impact on subsequent treatment outcomes is not known. Methods: 40 patients with advanced/unresectable HCC and Child Pugh score A have been enrolled in first and second-line clinical trials of anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs). HCC etiologies were: hepatitis C (32.5%), hepatitis B (7.5%), alcohol abuse (27.5%), other (32.5%). 7 received anti-PD-1 mAbs alone and 33 received combined regimens that included anti-PD-1 mAbs plus either anti-cytotoxic T lymphocyte antigen 4 (30.4%) or tyrosine kinase inhibitors (TKIs) (54.5%), or both (15.1%). We reviewed their liver function tests and HIRAEs onset was related to time to treatment failure (TTF). Results: Overall, 12 patients (30%) developed grade ≥ 3 hepatitis according to Common Toxicity Criteria for Adverse Events v. 4.03, resulting in 4 cases of grade 2 drug-induced liver injury per DILI Working Group criteria. Time between therapy initiation and hepatitis onset was 1.4 months (0.4-2.8) and median peak aminotransferase (AT) level was 258 IU/L (85-869). Out of 6 permanent treatment discontinuations due to adverse events (AEs), 4 were linked to hepatitis. Higher AT median levels at baseline were significantly linked to grade ≥ 3 hepatitis compared with lower grades (95 IU/L vs. 36 IU/L, respectively; p = 0.008). Etiology, age, treatment did not predict HIRAEs onset. TTF in patients in patients with grade ≥ 3 hepatitis was shorter than in the whole cohort (1.4 vs. 3.8 months, p = 0.041), while overall survival did not differ (p = 0.125). Conclusions: We observed a 30% incidence of clinically significant HIRAEs. HIRAEs represent the most frequent AEs leading to treatment discontinuation in patients with HCC undergoing treatments with immune checkpoint inhibitors. Baseline AT levels may identify patients at increased risk of grade ≥ 3 hepatitis.

scholarly journals Clinical Features of Liver Injury Induced by Immune Checkpoint Inhibitors in Japanese Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Koji Imoto ◽  
Motoyuki Kohjima ◽  
Tomonobu Hioki ◽  
Tomoyuki Kurashige ◽  
Miho Kurokawa ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Biopsy ◽  
Clinical Features ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Japanese Patients ◽  
Malignant Neoplasms ◽  
Drug Induced

Aim. Immune checkpoint inhibitors (ICIs) have improved the survival rate of patients carrying various malignant neoplasms. Despite their efficacy, ICIs occasionally induce liver injury as an immune-related adverse event (irAE). This study aimed to reveal the clinical features of the hepatic irAE in Japanese patients. Methods. Among 387 patients treated with ICIs, those who developed drug-induced liver injury were investigated. We also describe the histological findings and clinical courses of four patients with hepatic irAE who underwent liver biopsy. Results. Among the 56 patients with all-grade liver injury, only 11 (19.6%) showed hepatocellular-type liver injury, which resembled autoimmune hepatitis. Thirty-four patients (60.7%) developed cholestatic or mixed-type liver injury, although only one patient showed abnormal image findings in the bile duct. Most patients with grade ≤2 liver injury improved spontaneously, while two patients with biliary dysfunction required ursodeoxycholic acid or prednisolone. Among eight patients with grade ≥3 liver injury, three required no immunosuppressants and five were treated with prednisolone (three of five patients required other types of immunosuppressants). Four patients in the case series showed diverse clinical features in terms of hepatotoxic pattern, symptoms, and the interval time between the initiation of immunotherapy and the onset of the hepatic irAE. Conclusions. Our findings suggest that ICIs could cause microscopic biliary disorder without any abnormal image finding. Because the hepatic irAE presents diverse clinical features, liver biopsy is recommended to provide appropriate treatments.

scholarly journals Management of adverse events in cancer treatment with immune checkpoint inhibitors

2021 ◽  
Vol 64 (5) ◽  
pp. 358-365
Author(s):  
Myoung Joo Kang
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Organ Transplant ◽  
Chemotherapeutic Agents ◽  
Careful Consideration ◽  
The Body ◽  
Close Monitoring ◽  
Multiple Organs

The use of immune checkpoint inhibitors is associated with a spectrum of immune-related adverse events related to the mechanism of action which is quite different from that of cytotoxic chemotherapy. Adverse effects can affect multiple organs of the body and are most common in the skin, gastrointestinal tract, lungs, and endocrine tissues, including the thyroid, adrenal gland, pituitary gland, as well as musculoskeletal, renal, nervous, hematologic, cardiovascular, and ocular systems. Any changes should be considered as being related to treatment with immune checkpoint inhibitors. Adverse events are very infrequent, but may be very serious and, even lethal, such as neurological disorders and myocarditis. When compared with standard chemotherapeutic agents, programmed death 1/programmed deathligand 1inhibitors are associated with a lower incidence of bone marrow suppression, anorexia, nausea, vomiting, and diarrhea. Immune checkpoint inhibitor therapy can usually continue in the presence of mild immune-related adverse events with close monitoring. However, moderate to severe immune-related adverse events may be associated with a severe decline in organ function and quality of life, and may result in fatal outcomes. Hence, these toxicities require early detection and proper management. The management of immune-related adverse events usually involves corticosteroid therapy or the use of immunomodulators. The use of immune checkpoint inhibitors in patients with preexisting autoimmune disease or a history of prior organ transplant should include careful consideration and a robust discussion of potential risks and benefits.

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