scholarly journals A case report of immune checkpoint inhibitor-related steroid-refractory myocarditis and myasthenia gravis-like myositis treated with abatacept and mycophenolate mofetil

2021 ◽  
Author(s):  
Mette S Jespersen ◽  
Søren Fanø ◽  
Christian Stenør ◽  
Anne Kirstine Møller
Keyword(s):  
Mycophenolate Mofetil ◽  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Laboratory Findings ◽  
Steroid Refractory

Abstract Background Immune checkpoint inhibitor (ICI)-related myocarditis is an uncommon but potentially fatal immune-related adverse event. Corticoid-resistant myocarditis induced by ICI is an important therapeutic challenge. Case Summary Here we present a case of steroid-refractory ICI-related myocarditis and myositis treated with abatacept and mycophenolate mofetil (MMF). A 57-year-old male with metastatic renal cell carcinoma was diagnosed with immune-related myocarditis and myasthenia gravis-like myositis after first dose of combination immune checkpoint inhibitors with nivolumab (anti-programmed cell death-1) plus ipilimumab (anti-cytotoxic T-lymphocyte-associated antigen-4). Twelve days after ICI he was admitted to the hospital due to palpitations, headache, and pain in the extremities. Laboratory findings revealed elevated inflammatory markers and cardiac enzymes. Electrocardiogram showed first-degree AV-block and right bundle branch block which developed into complete heart block within 48 hours. Because of clinical and paraclinical deterioration despite immediate initiation of methylprednisolone abatacept and MMF was added. Following, gradual subjective improvement and termination of arrythmia led to discharge of the patient from the hospital 6 weeks after introduction of ICI. Discussion The key treatment of ICI-related myocarditis is glucocorticoid. For steroid-refractory myocarditis supplementary immune suppressive agents are recommended. Yet, data still relies on case reports and case series, due to lack of prospective studies. In this case the use of abatacept and MMF led to resolution of steroid-resistant ICI-related myocarditis and myositis.

Predictors of steroid-refractory immune checkpoint inhibitor associated myocarditis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Power ◽  
W Meijers ◽  
C Fenioux ◽  
Y Tamura ◽  
A Asnani ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Adverse Events ◽  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Funding Source ◽  
Daily Dose ◽  
Age And Sex ◽  
Steroid Refractory

Abstract Background/Introduction Immune checkpoint inhibitor (ICI)-associated myocarditis has a high mortality rate of approximately 50%. Clinical decompensation often occurs despite first-line treatment with corticosteroids. Factors associated with steroid failure are currently unknown. Purpose To identify predictors of steroid failure in patients with ICI-associated myocarditis. Methods We developed a web-based registry to collect and study 157 cases with clinical manifestations of ICI-associated myocarditis across 16 countries. Steroid failure was defined as patients who were escalated to immunomodulators after ≥1mg/kg daily dose of prednisone or had in-hospital death due to myocarditis despite ≥1mg/kg daily dose of prednisone. Steroid response was defined as all other patients treated with steroids without escalation to immunomodulators and without death due to myocarditis. A multivariate logistic model accounting for age and sex was used to predict association with steroid failure. Results Compared to steroid responsive cases, steroid failure was more likely to result in fulminant myocarditis (56.7% vs 19.6%, OR=5.37 [2.62–10.98] p<0.001) and all-cause in-hospital mortality (49.1% vs 12.9%, OR=6.50 [2.86–14.73] p<0.001) with shorter time from presentation to death (27.5 vs 43.0 days HR: 2.56 [1.45–4.50] p=0.001). When adjusting for age and sex, cases were more likely to be steroid-refractory if they were female (46.7% vs 30.1%, OR=2.77 [1.31–5.85] p=0.007), higher body mass index (27.2 vs 22.0, OR=1.09 [1.01–1.18] p=0.012), had higher intake creatine kinase (2800.5 vs 528.0 U/L, OR=1.48 [1.14–1.90] p=0.003) had higher intake troponin T (1.40 vs 0.25 ng/mL OR=1.63 [1.00–2.64] p=0.049), or had one or more concomitant non-cardiac immune-related adverse event (90.0% vs 74.2%, OR=3.10 [1.14–8.25] p<0.026). The only immune-related adverse events independently associated with steroid failure in myocarditis were myasthenia gravis-like syndrome (26.7% vs 8.2%, OR=3.84 [1.47–10.10] p=0.006) and myositis (45.0% vs 24.7%, OR=2.38 [1.16–4.92] p=0.018). Steroid failure was not significantly associated with cardiovascular or autoimmune history but was associated with a history of thymoma (12.0% vs 2.6%, OR=18.86 [0.10–356.7] p=0.05) Conclusion(s) Features such as female sex, high body mass index, and pre-existing thymoma as well as findings of elevated cardiac biomarkers and other non-cardiac immune-related adverse events – particularly myositis and myasthenia gravis-like syndrome – may represent a steroid-refractory phenotype of ICI-associated myocarditis. These results suggest that a multidisciplinary approach to diagnosing concomitant non-cardiac immune related adverse events is key to risk-stratifying ICI-associated myocarditis. Forrest Plot Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): National Institutes of Health

First use of tofacitinib to treat an immune checkpoint inhibitor-induced arthritis

2021 ◽  
Vol 14 (2) ◽  
pp. e238851
Author(s):  
Kieran Murray ◽  
Achilleas Floudas ◽  
Ciara Murray ◽  
Aurelie Fabre ◽  
John Crown ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Inflammatory Arthritis ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Personalised Medicine ◽  
Case Series ◽  
Janus Kinase ◽  
Sustained Remission ◽  
Cellular Immune

Immune checkpoint inhibitors have revolutionised cancer treatment; however, immune-related adverse events do occur, with up to 7% developing inflammatory arthritis. Common rheumatoid arthritis therapies such as methotrexate, prednisolone and biologics have been used to treat this arthritis in small, uncontrolled case series with varying success. In this case of personalised medicine, we report the first use of tofacitinib, a small molecular inhibitor of the Janus kinase-signal transducer and activator of transcription pathway, to treat checkpoint inhibitor-related inflammatory arthritis. This resulted in a rapid clinical response and complete, sustained remission of the arthritis with associated marked reduction in synovial molecular and cellular immune response.

scholarly journals Primary Adrenal Insufficiency during Immune Checkpoint Inhibitor Treatment: Case Reports and Review of the Literature

2020 ◽  
Vol 13 (2) ◽  
pp. 621-626
Author(s):  
Carlos Salinas ◽  
Alex Renner ◽  
Carlos Rojas ◽  
Suraj Samtani ◽  
Mauricio Burotto
Keyword(s):  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Review Of The Literature ◽  
Primary Adrenal Insufficiency ◽  
High Degree ◽  
Inhibitor Treatment

As the indications and clinical use of immune checkpoint inhibitors increase, it is expected that we will face some of their less frequently reported complications. Primary adrenal insufficiency is one of them, and given its unspecific symptoms and potentially serious consequences, it is important to have a high degree of clinical suspicion. We present 3 cases and a review of the literature concerning its main clinical characteristics, diagnostics, and management.

Immune checkpoint inhibitor-mediated myasthenia gravis with focal subclinical myocarditis progressing to symptomatic cardiac disease

2020 ◽  
Vol 13 (5) ◽  
pp. e232920 ◽  
Author(s):  
Phillip John Leaver ◽  
Helena Sung-In Jang ◽  
Stephen Thomas Vernon ◽  
Suran Loshana Fernando
Keyword(s):  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Fatal Complication ◽  
Adverse Health Outcomes ◽  
Clinical Presentations ◽  
Organ Specific ◽  
Delayed Recognition

The advent of immune checkpoint inhibitors (ICIs) for cancer therapy has heralded increasing frequency of immune-related adverse events including endocrinopathies, hepatitis, colitis and rarely myocarditis and myasthenia gravis (MG). The heterogeneity in clinical presentations regardless of organ-specific involvement can lead to delayed recognition and management of these events and adverse health outcomes. We describe a case of ICI-induced subclinical focal myocarditis that was recognised and treated in the broader context of MG. It is essential that patients with ICI-induced MG should be screened and monitored for myocarditis, a potentially fatal complication.

scholarly journals Mycophenolate mofetil as a successful treatment of corticosteroid-resistant immune checkpoint inhibitor-induced hepatitis

2020 ◽  
Vol 2020 (4-5) ◽  
Author(s):  
Kenji Nakano ◽  
Masatoshi Nishizawa ◽  
Naoki Fukuda ◽  
Tetsuya Urasaki ◽  
Xiaofei Wang ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Salvage Treatment ◽  
Japanese Male ◽  
Alternative Treatment Option ◽  
Old Japanese

Abstract Immune checkpoint inhibitors (ICIs) are now widely used to many malignant diseases, but some patients suffer from immune-related adverse events during or after ICI treatments. The monoclonal antibody infliximab is usually chosen as a salvage treatment to combat corticosteroid-resistant adverse events, but infliximab is not recommended as a response to hepatitis because of the potential risk of liver failure. An alternative treatment option has not been established. We treated a head and neck cancer patient (a 50-year-old Japanese male) who suffered from corticosteroid-resistant hepatitis during treatment with nivolumab, an anti-PD-1 ICI, and that was recovered by mycophenolate mofetil salvage therapy.

scholarly journals Rituximab for Immune Checkpoint Inhibitor Myasthenia Gravis

2020 ◽  
Author(s):  
Neha Verma ◽  
Muhammad Jaffer ◽  
Esha Sharda ◽  
Yolanda Pina ◽  
Asha Ramsakal ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
Stage Iiic ◽  
Progressive Dyspnea ◽  
Positive Serum ◽  
New Onset

Abstract Importance: The use of immune checkpoint inhibitors (ICIs) in the treatment of multiple cancers have gained prominence due to their high efficacy. However, neurological immune-related adverse events (irAEs) such as myasthenia gravis (MG) have been associated with ICI therapy. Most of these neurological irAEs are rare, and in many cases, their diagnoses and management can be challenging. Observations: We present a case of a 70-year-old woman with Stage IIIC melanoma who developed a new onset of gradually progressive dyspnea, diplopia, and bilateral ptosis following treatment with one cycle of nivolumab and ipilimumab (Nivo+Ipi). She was diagnosed with MG via positive serum acetylcholine receptor (AChR) antibodies. She had developed a severe dyspnea at rest, which was refractory to multiple immune-suppressive therapies including prednisone, pyridostigmine, and intravenous immunoglobulin (IVIG). Subsequently, she was treated with rituximab 375 mg/m2 monthly every 4 weeks with significant improvement of her symptoms within 48 hours each time.Conclusions and Relevance: As the implementation of immunotherapy increases in medical practice, irAEs may become more apparent. When first-line therapies are not adequate, other alternative therapies should be explored. This case of MG as an irAE shows that rituximab can provide potential benefit to treat patients with immunotherapy-induced MG who are refractory to other standard treatments. Prospective studies are needed to further evaluate the efficacy of Rituximab irAEs.

scholarly journals Carpal Tunnel Syndrome as an Unusual Immune Checkpoint Inhibitor Adverse Effect: A Case Series and Review of the Literature

2020 ◽  
Vol 5 (11) ◽  
pp. 550-553
Author(s):  
Walid Shalata ◽  
Alexander Yakobson ◽  
Ismaell Massalha ◽  
Roxana D. Grinberg ◽  
Iris M. Goldstein ◽  
...  
Keyword(s):  
Carpal Tunnel Syndrome ◽  
Carpal Tunnel ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Standards Of Care ◽  
Adjuvant Immunotherapy ◽  
Tunnel Syndrome

While immune checkpoint inhibitors (ICIs) have transformed standards of care and drastically improved patient prognoses in several malignant diseases, a range of immune related adverse events (irAEs) from ICIs have been observed. This case series describes the clinical course of three patients with unusual immune checkpoint-inhibitor (ICI) induced toxicities. These three patients developed carpal tunnel syndrome (CTS) while on ICI therapy. The first patient was a 79 year-old male who received neo-adjuvant chemo-immunotherapy and adjuvant immunotherapy (atezolizumab) for stage II-B lung adenocarcinoma, the second patient was a 70 year-old female who received immunotherapy only (nivolumab) for stage IV renal cell carcinoma and the third patient was a 71 year-old male who received adjuvant immunotherapy (nivolumab) for stage 2-A melanoma. The patients developed carpal tunnel syndrome with severe neuropathy as a result of therapy. All patients had complete symptomatic relief when treated with either corticosteroids or intravenous immunoglobulins for CTS.

Immune checkpoint inhibitor–associated renal amyloid A amyloidosis: A case series and review of the literature

2020 ◽  
Vol 4 (1-2) ◽  
pp. 52-58 ◽  
Author(s):  
Sebastian Lapman ◽  
William L Whittier ◽  
Rushang Parikh ◽  
Yuriy Khanin ◽  
Vanesa Bijol ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Kidney Injury ◽  
The Other ◽  
Primary Role ◽  
Amyloid A ◽  
Immune Mediated

Immune checkpoint inhibitors are a cornerstone in the management of many oncological disorders, and their indications continue to grow. However, as with any therapy we must remain vigilant of the possible adverse effects. Although interstitial nephritis is a reported cause of immune checkpoint inhibitor–related kidney injury, immune-mediated glomerular disease has rarely been described. Here, we present three patients being treated with checkpoint inhibitors for colon cancer, metastatic squamous cell carcinoma of the lung, and melanoma, who developed biopsy-proven amyloid A amyloidosis. In all three cases, the malignancies were in remission, yet continued inflammation and amyloid deposition occurred, pointing toward a primary role of the immune checkpoint inhibitor. Treatment generally remains a challenge due to a paucity of reported cases, thus further study of cytokine profile is prudent. In one case, the patient was given tocilizumab in the setting of elevated interleukin-6 levels; unfortunately no appreciable renal benefit was noted and the patient became dialysis dependent. In the other two cases, the patients were treated with colchicine and steroids. One patient had a substantial decrease in proteinuria and inflammatory markers while no significant response was noted in the other. Knowledge of immune checkpoint inhibitor–associated amyloid A amyloidosis is important for the oncologist and the nephrologists.

scholarly journals Immune checkpoint inhibitor-associated myasthenia gravis, myositis, and myocarditis overlap syndrome

2021 ◽  
Vol 46 ◽  
pp. 51-55 ◽  
Author(s):  
Demis N. Lipe ◽  
Elkin Galvis-Carvajal ◽  
Eva Rajha ◽  
Adriana H. Wechsler ◽  
Susan Gaeta
Keyword(s):  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Overlap Syndrome
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