Successful Treatment of Myasthenia Gravis Following PD-1/CTLA-4 Combination Checkpoint Blockade in a Patient With Metastatic Melanoma

Werner, Jan-Michael; Schweinsberg, Viola; Schroeter, Michael; Reutern, Boris von; Malter, Michael P.; Schlaak, Max; Fink, Gereon R.; Mauch, Cornelia; Galldiks, Norbert

doi:10.3389/fonc.2019.00084

Cited by 17 publications

(12 citation statements)

References 12 publications

(17 reference statements)

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“…Based on our experience and previously documented literature, we suggest that a multidisciplinary approach [2] should be implemented while treating patients with ICI so that life-threatening adverse effects could be managed in a time-sensitive manner. The team should specifically include neurologists and neuro-oncologists [18], as neurotoxicity can be challenging to diagnose mainly when these agents are administered and monitored by non-neurological professionals hence the risk of underreporting stays high [19]. A standardized stepwise checklist [19] should also be developed to detect the neurological irAEs early, particularly in those hospitals where neurologists are either not readily available or are not directly involved in the care and monitoring of cancer patients [19].…”

Section: Discussionmentioning

confidence: 99%

Nivolumab, a Double-Edged Sword: A Case Report of Nivolumab-Induced Myasthenia Gravis

et al. 2021

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Nivolumab is a checkpoint inhibitor approved to treat various solid organs malignancies. Although checkpoint inhibitors are very efficacious, these medications are also associated with a variety of side effects that could be life-threatening. We present a case of nivolumab-induced myasthenia gravis in a patient with stage IV esophageal cancer, who was found to have generalized weakness, blurry vision, diplopia, and later developed acute hypoxic respiratory failure with subsequent intubation. The patient was treated with intravenous immunoglobulin and plasmapheresis, and later started on pyridostigmine and high-dose steroids with minimal improvement. Goals of care were discussed with the patient and family, and the decision was made to discharge the patient home with hospice care. Nivolumab-induced myasthenia gravis is very aggressive with a poor prognosis if not appropriately managed in time. Hence we strongly recommend a multidisciplinary approach, including neurologists, to monitor patients on nivolumab therapy to reduce morbidity and mortality associated with it.

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Section: Discussionmentioning

confidence: 99%

Nivolumab, a Double-Edged Sword: A Case Report of Nivolumab-Induced Myasthenia Gravis

et al. 2021

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“…Some neuromuscular iRAEs cases, especially in those with preexisting immune disease, seem more likely to suffer from overlap-syndromes indicating myositis, myocarditis and MG present at the same time, and have higher frequencies of myasthenic crisis and fatal deterioration (10)(11)(12). The combination of checkpoint blockade is also much easier to have lifethreatening adverse effects than mono-therapy (13,14). In a large retrospective study of 9,869 cancer patients in Japan with nivolumab, 12 cases (0.12%) developed MG in 6 weeks after nivolumab and rapidly deteriorated despite immediate management, two of them died from myocarditis and myasthenic crisis.…”

Section: Discussionmentioning

confidence: 99%

Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma

Qiu¹,

Zhang²,

Lin³

et al. 2020

Ann Transl Med

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Immune checkpoint inhibitors (ICIs) have improved clinical outcomes with a number of advanced malignancies. However, diverse immune-related adverse events (iRAEs) occurred with the widespread use of ICIs, some of which are rarely and life-threatening. Here we report a 66-year-old patient with lung adenocarcinoma who received two doses of sintilimab, a human monoclonal antibody against programmed cell death-1 (PD-1), experienced a fatal storm of iRAEs. He was admitted to the intensive care unit (ICU) by immune induced-myositis/myocarditis and rhabdomyolysis. Despite immediate immunosuppressive therapy with methylprednisolone (MP) and immunoglobulin intravenously, he developed into myositis-myasthenia gravis (MG) overlap syndrome complicated with myasthenia crisis. We commenced plasma exchange (PLEX), mechanical ventilation, immunosuppressive therapy, as well as other supportive therapies. Three months later, the patient's serum creatine phosphate kinase (CPK) and anti-acetylcholine receptor antibody (anti-AChR-Ab) returned to normal despite tumor progression. Herein we discuss the incidence, operating mechanism and management strategies of the fatal iRAEs. Early admission to the ICU and multidisciplinary collaborative treatment for unstable patients with iRAEs could help to achieve a favorable outcome.

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“…Early multidisciplinary input is invaluable to management of these complex toxicities. As with all irAEs, ICI-induced MG presents with a spectrum of severity with some patients only developing limited symptoms that respond to immunosuppression and pyridostigmine [25,26]. Overall, ICI-induced MG tends to have a more aggressive clinical course than non-ICI-related disease and patients often show signs of myositis and myocarditis [20,27].…”

Section: Discussionmentioning

confidence: 99%

Severe combined cardiac and neuromuscular toxicity from immune checkpoint blockade: an institutional case series

Arora¹,

Talamo

Dillon

et al. 2020

Cardio-Oncology

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Background Immune checkpoint inhibition is part of standard systemic management for many advanced malignancies. Toxicities from this treatment approach are unpredictable, though usually reversible with management per established guidelines. Some patients suffer major morbidity and treatment-related mortality from these agents in an unpredictable manner. Cardiac and neurologic complications are rare, but can result in serious clinical consequences. Methods We describe the presentation, management, and outcomes of eight sequential cases of combined cardiac and neurologic toxicities resulting in severe illness and demonstrating lack of rapid response to immunosuppression. Results Our cohort consisted of six males and two females with an average age of 73.5 years (61–89 years). There were four patients with melanoma, and one patient each with urothelial carcinoma, renal cell carcinoma, breast cancer, and non-small cell lung cancer. Four patients received combination immunotherapy and four patients received monotherapy. The median time to presentation from treatment initiation was 27 days (11–132 days). All patients had a cardiovascular and neurologic toxicity, and most had hepatitis and myositis. The cardiac signs and symptoms were the prominent initial features of the clinical presentation. Each patient was managed by a multidisciplinary team and received a range of immunosuppressive agents. All patients died as a consequence of the immune related adverse events. Conclusions The evaluation of patients with cardiac adverse events from immunotherapy, should include assessment of overlapping toxicities such as myasthenia gravis and myositis. Providers should be aware of the potential for an extended duration of disability and slow improvement for certain toxicities as these expectations may factor prominently in goals of care decisions.

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Successful Treatment of Myasthenia Gravis Following PD-1/CTLA-4 Combination Checkpoint Blockade in a Patient With Metastatic Melanoma

Cited by 17 publications

References 12 publications

Nivolumab, a Double-Edged Sword: A Case Report of Nivolumab-Induced Myasthenia Gravis

Nivolumab, a Double-Edged Sword: A Case Report of Nivolumab-Induced Myasthenia Gravis

Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma

Severe combined cardiac and neuromuscular toxicity from immune checkpoint blockade: an institutional case series

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