scholarly journals Hypokalemic Paralysis Secondary to Immune Checkpoint Inhibitor Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Pragathi Balakrishna ◽  
Augusto Villegas
Keyword(s):  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
High Serum ◽  
Admission Diagnosis ◽  
High Dose ◽  
Immune Mediated ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Introduction of immune checkpoint inhibitors (ICIs) has led to significant improvements in the treatment of multiple malignancies. Anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) are two essential ICIs that have been FDA approved since 2011. As the use of immunotherapy in melanoma and other malignancies increases, the potential of adverse events also increases. Overall, anti-PD-1 agents are well tolerated. In rare instances, colitis, endocrinopathies, skin, and renal toxicities have been observed. A 58-year-old male with a history of stage 4 cutaneous melanoma presented with quadriplegia while on nivolumab. Routine blood test revealed low potassium, low bicarbonate, and high serum creatinine. Admission diagnosis included hypokalemia, acute kidney injury, and renal tubal acidosis. The offending drug was discontinued, and the patient was started on high-dose corticosteroids. On discharge, paralysis was resolved. Renal function and potassium were normalized. Nivolumab was discontinued, and he was started on pembrolizumab. Literature suggests that, although rare, patients receiving ICE may develop immune-mediated nephritis and renal dysfunction. The mainstay of immune-related adverse event (irAE) management is immune suppression. Hence, given the increasing frequency of immunotherapy use, awareness should be raised in regard to irAEs and their appropriate management.

scholarly journals Development of Nivolumab/Ipilimumab-Associated Autoimmune Nephritis during Steroid Therapy

2021 ◽  
pp. 270-274
Author(s):  
Ellen Gebauer ◽  
Wibke Bechtel-Walz ◽  
Christoph Schell ◽  
Michelle Erbel ◽  
Gerd Walz ◽  
...  
Keyword(s):  
Steroid Therapy ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Oral Steroid ◽  
High Dose ◽  
Immune Mediated

Immunotherapy using immune checkpoint inhibitors revolutionized therapies for a variety of malignancies. Nivolumab, an antibody blocking programmed cell death 1 protein, and ipilimumab that blocks cytotoxic T-lymphocyte-associated protein 4 effectively target tumor cells by disinhibiting the endogenous immune response. At the same time, unrestrained T-cell activation may trigger a range of immune-mediated side effects including kidney injury. Steroid therapy constitutes the mainstay of treatment of these adverse events, but dosage, route of administration, and approach to nivolumab re-exposure remain unclear. Here, we report the case of a 72-year-old male patient who developed severe nivolumab/ipilimumab-associated acute kidney injury while on oral steroid therapy for immune-mediated colitis. Acute interstitial nephritis was confirmed by renal biopsy. Administration of high-dose intravenous steroid doses was required to revert declining renal function.

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.

scholarly journals Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

2020 ◽  
Vol 38 (6) ◽  
pp. 576-583 ◽  
Author(s):  
Hamzah Abu-Sbeih ◽  
David M. Faleck ◽  
Biagio Ricciuti ◽  
Robin B. Mendelsohn ◽  
Abdul R. Naqash ◽  
...  
Keyword(s):  
Adverse Events ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy ◽  
Inflammatory Bowel

PURPOSE The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

scholarly journals A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review

2020 ◽  
Vol 8 ◽  
pp. 2050313X1989770 ◽  
Author(s):  
Anastasia Politi ◽  
Dimas Angelos ◽  
Davide Mauri ◽  
George Zarkavelis ◽  
George Pentheroudakis
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Skin Lesions ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Programmed Death ◽  
History Of ◽  
Programmed Death 1 ◽  
Cessation Of Treatment

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis—a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.

scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

scholarly journals SAT0536 IMMUNE CHECKPOINT INHIBITOR THERAPY IN PATIENTS WITH PREEXISTING SARCOIDOSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1225.2-1226
Author(s):  
X. Pundole ◽  
O. Lambotte ◽  
M. Ramos-Casals ◽  
M. Suarez-Almazor
Keyword(s):  
Autoimmune Diseases ◽  
Medical Record ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Cancer Center ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Background:Immune checkpoint inhibitors (ICI) have changed the treatment landscape of many cancer types, but are also associated with development of immune-related adverse events, includingde novosarcoid like reactions. However, little is known about the use of ICI therapy in patients with preexisting sarcoidosis as patients with preexisting autoimmune diseases have been systematically excluded from clinical trials of ICI therapy due to concerns of heightened toxicities. Emerging research suggests that ICI therapy can be considered in some patients with autoimmune diseases.1Objectives:To determine the risk of sarcoidosis exacerbation or flare in patients with preexisting sarcoidosis receiving ICI therapy.Methods:We conducted a retrospective cohort study of patients seen at The University of Texas MD Anderson Cancer Center between 2016-2019. Patients were included in the cohort if they received one of 7 ICI therapies (ipilimumab, nivolumab, pembrolizumab, durvalumab, avelumab, atezolizumab, or cemiplimab) and had an International Classification of Disease version 10 code of sarcoidosis (D86.*), prior to the ICI initiation, with diagnosis confirmed in medical record by treating physicians. A sarcoidosis diagnosis was considered “possible” if the medical record documented a history of sarcoidosis, “probable” if a history of biopsy proven sarcoidosis was mentioned, and “definitive” if histological evidence was available. Frequency of flares and outcomes of patients after receiving ICI were collected.Results:During the study timeframe a total of 32 patients with preexisting sarcoidosis received ICI therapy. Nine patients (28%) had a definitive diagnosis of sarcoidosis, 12 (37%) had a probable diagnosis and 11 (35%) had a possible diagnosis of sarcoidosis. The mean time between diagnosis of sarcoidosis and initiation of ICI therapy was 13 years (range: <1 to 51 years). Twenty-seven patients (84%) received monotherapy and five patients (16%) received combination or sequential ICI therapy. Of the 32 patients, one patient with a 20-year remote history of sarcoidosis, never treated, developed a clinically symptomatic exacerbation of sarcoidosis one month after the initial dose of atezolizumab, with increased hilar nodules on imaging, skin nodules, arthritis and uveitis. Biopsy of a lymph node showed non-necrotizing granulomas, and biopsy of the skin panniculitis. The patient also developed colitis thought to be an immune-related adverse event. Atezolizumab was discontinued after 3 doses. Patient was treated with prednisone and azathioprine.Conclusion:Patients with a remote history of stable sarcoidosis at the time of ICI therapy infrequently develop a flare of their sarcoidosis. The risk of flares in patients with active sarcoidosis requiring immunosuppression at the time of ICI initiation is unknown.References:[1]Kennedy LC, Bhatia S, Thompson JA, Grivas P. Preexisting autoimmune disease: implications for immune checkpoint inhibitor therapy in solid tumors. Journal of the National Comprehensive Cancer Network. 2019 Jun 1;17(6):750-7.Acknowledgments:NoneDisclosure of Interests:Xerxes Pundole: None declared, Olivier Lambotte Consultant of: BMS France, MSD, Astra Zeneca, Incyte, Manuel Ramos-Casals: None declared, Maria Suarez-Almazor: None declared

Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective

2018 ◽  
Vol 71 (8) ◽  
pp. 665-671 ◽  
Author(s):  
Dipti M Karamchandani ◽  
Runjan Chetty
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Immune Mediated ◽  
Self Tolerance ◽  
Novel Drugs ◽  
Cell Death Protein

Immune checkpoint inhibitors (CPIs) are a relatively new class of ‘miracle’ dugs that have revolutionised the treatment and prognosis of some advanced-stage malignancies, and have increased the survival rates significantly. This class of drugs includes cytotoxic T lymphocyte antigen-4 inhibitors such as ipilimumab; programmed cell death protein-1 inhibitors such as nivolumab, pembrolizumab and avelumab; and programmed cell death protein ligand-1 inhibitors such as atezolizumab. These drugs stimulate the immune system by blocking the coinhibitory receptors on the T cells and lead to antitumoural response. However, a flip side of these novel drugs is immune-related adverse events (irAEs), secondary to immune-mediated process due to disrupted self-tolerance. The irAEs in the gastrointestinal (GI) tract/liver may result in diarrhoea, colitis or hepatitis. An accurate diagnosis of CPI-induced colitis and/or hepatitis is essential for optimal patient management. As we anticipate greater use of these drugs in the future given the significant clinical response, pathologists need to be aware of the spectrum of histological findings that may be encountered in GI and/or liver biopsies received from these patients, as well as differentiate them from its histopathological mimics. This present review discusses the clinical features, detailed histopathological features, management and the differential diagnosis of the luminal GI and hepatic irAEs that may be encountered secondary to CPI therapy.

scholarly journals Immune checkpoint inhibitors for the treatment of glioblastoma: Where we are

2020 ◽  
Vol 10 (1) ◽  
pp. 7
Author(s):  
Bryan Lu ◽  
Senxi Du ◽  
Xiao-Tang Kong
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Human Cancer ◽  
Current Status ◽  
History Of

Despite a history of frequent challenges and roadblocks, there has been recent excitement in the treatment of human cancer, specifically regarding the remarkable efficacy of various immune checkpoint inhibitors including programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockers in treating metastatic melanoma, non-small cell lung cancer, and other malignant growths. However, treatment of glioblastoma multiforme (GBM) with immune checkpoint inhibitors so far has not been shown to be as successful in several randomized clinical trials as in other cancer with the exception of one pilot study that found promising results by neoadjuvant administration of Pembrolizimab for the treatment of recurrent GBM. Our article will review the current status of immune checkpoint inhibitors for the treatment of GBM.

Evaluation of arthralgias in adult oncology patients receiving immune checkpoint inhibitors

2019 ◽  
Vol 25 (8) ◽  
pp. 1867-1872 ◽  
Author(s):  
Jenessa Lee ◽  
Anastasia Graham ◽  
Amy Sion
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Inhibitor Therapy ◽  
Time To Event ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors are being commonly used as anticancer therapies to treat malignancies. Immune checkpoint inhibitors have been associated with numerous immune-related adverse events (irAEs). IrAEs are well documented; however, rheumatic irAEs are infrequently reported in published literature. The objective of this single-center retrospective chart review study was to evaluate the incidence of arthralgias with immune checkpoint inhibitor therapy as well as the management of these immune-related events. Patients were included if they received one or more doses of nivolumab, pembrolizumab, atezolizumab, ipilimumab, or a combination of agents within the last year. Exclusion criteria included documented history of autoimmune disease, off-label use of immune checkpoint inhibitor, and non-FDA-approved weight-based dosing. This study included 98 patients for review and identified 11 patients that developed arthralgias with immune checkpoint inhibitor therapy. Median time to event was 63 days. Seven patients were treated with corticosteroids. Immune checkpoint inhibitor therapy was held in six patients with arthralgias. Inflammatory markers were collected for six patients and elevated in four of these cases. One patient was referred to rheumatology. The three patients who had grading of arthralgias were not managed optimally according to guideline recommendations. These findings show that 11% of patients treated with immune checkpoint inhibitors had documented arthralgias, consistent with previous reports in the literature. Also, the report shows that management and treatment of these events at our institution was not consistent between providers. Lastly, collaboration with rheumatology may be essential in managing arthralgias and other rheumatologic irAEs.

292 Immune checkpoint inhibitor induced overlapping cardiac and neuromuscular toxicities: Highlight of early diagnosis, early initiation of immunosuppressive therapy and multidisciplinary management

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A319-A319
Author(s):  
HoWai Siu ◽  
Robert O’Neill ◽  
Matthew Tong ◽  
JunHee Hong ◽  
Carole Harris ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Myasthenia Gravis ◽  
Immunosuppressive Therapy ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Early Initiation ◽  
High Dose ◽  
Multidisciplinary Management ◽  
Steroid Sparing

BackgroundThe use of immune checkpoint inhibitors (ICIs) against programmed cell death protein -1 (PD-1), its ligand (PD-L1) and cytotoxic T- lymphocyte associated protein 4 (CTLA4) have been increasing. Immune induced myocarditis, myositis and myasthenia gravis are rare but potentially severe complications from these agents. Here we report 3 cases of ICI induced myocarditis, myositis, myasthenia gravis and transaminitis as a cluster, and highlights early diagnosis, prompt initiation of steroid sparing immunosuppressive therapy and multidisciplinary management.MethodsThree patients received anti-PD-1 ICIs developed cardiac, neuromuscular complications and transaminitis within 4 weeks after initiation. Clinical data were retrospectively reviewed from medical records.ResultsAll patients had elevated cardiac enzymes, developed complete heart block and underwent coronary catheterisation and pacemaker insertion. All patients developed myositis and myasthenia gravis (table 1) and were managed by multi-disciplinary team involving oncology, cardiology and neurology. Single-fibre electromyography was performed to confirm presence of myositis. One of three patients had positive acetylcholinesterase antibody, anti- muscle specific kinase antibody was negative in all cases. All patients developed grade 2–3 transaminitis with normal bilirubin. All patients received high-dose steroids. Steroid sparing therapy including intravenous immunoglobulin and mycophenolate mofetil were used early in 2 cases and was associated with rapid recovery of toxicities.Abstract 292 Table 1Patient characteristics, management and outcome of ir-AEsConclusionsICI induced myocarditis can be associated with myositis, myasthenia gravis and transaminitis. A high index of suspicion, comprehensive investigations and early involvement of multi-disciplinary teams are key to early accurate diagnosis. In steroid refractory cases, we propose early initiation of steroid sparing immunosuppressive therapy after 3 days.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

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