Myasthenia Gravis Induced by Nivolumab in Patients with Non-Small-Cell Lung Cancer: A Case Report and Literature Review

Hasegawa, Yoshikazu; Kawai, Shigeto; Ota, Takayo; Tsukuda, Hiroshi; Fukuoka, Masahiro

doi:10.2217/imt-2017-0043

Cited by 23 publications

(18 citation statements)

References 30 publications

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“…In our case, monotherapy with nivolumab was sufficient to trigger a Grade 2 MG and, as described by Hasegawa et al [10], neurological symptoms were associated with transaminase elevation. The positivity of acetylcholine receptor antibodies and the neurological evaluation were essential to confirm the immune-related hypothesis [4].…”

Section: Literature Review and Discussionsupporting

confidence: 77%

“…In a case of nivolumab-induced MG reported by Hasegawa et al [10], the patient presented also with creatine phosphokinase (CPK) and transaminase elevation. In our case, a central nervous system MRI showed a dimensional reduction of the brain metastasis and of the associated edema, without any alterations that might explain the patient’s symptoms and signs and acetylcholine receptor antibodies were normal.…”

Section: Literature Review and Discussionmentioning

confidence: 99%

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PD-1 Inhibitors-Related Neurological Toxicities in Patients with Non-Small-Cell Lung Cancer: A Literature Review

Mirabile

Brioschi

Ducceschi

et al. 2019

Cancers

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The advent of immune checkpoint inhibitors gave rise to a new era in oncology and general medicine. The increasing use of programmed death-1 (PD-1) inhibitors in non-small cell lung cancer and in other malignancies means clinicians have to face up to new challenges in managing immune-related adverse events (irAEs), which often resemble autoimmune diseases. Neurological irAEs represent an emerging toxicity related to immunotherapy, and it is mandatory to know how to monitor, recognize, and manage them, since they can rapidly lead to patient death if untreated. Guidelines for the diagnosis and treatment of these irAEs have been recently published but sharing some of the most unusual clinical cases is crucial, in our opinion, to improve awareness and to optimize the approach for these patients. A literature review on the diagnosis and treatment of immune-related neurotoxicity’s has been conducted starting from the report of four cases of neurological irAEs regarding cases of polyneuropathy, myasthenia gravis, Bell’s palsy, and encephalopathy, all of which occurred in oncological patients receiving PD-1 inhibitors (pembrolizumab and nivolumab) for the treatment of non-oncogene addicted advanced non-small cell lung cancer. The exclusion of other differential diagnoses and the correlation between the suspension of immunotherapy and improvement of symptoms suggest that immunotherapy could be the cause of the neurological disorders reported.

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Section: Literature Review and Discussionsupporting

confidence: 77%

Section: Literature Review and Discussionmentioning

confidence: 99%

PD-1 Inhibitors-Related Neurological Toxicities in Patients with Non-Small-Cell Lung Cancer: A Literature Review

Mirabile

Brioschi

Ducceschi

et al. 2019

Cancers

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“…In mid-November 2016, he had fatigue, and a sensation of weakness in his systemic muscles. Because of the possible onset of myasthenia gravis, a known side effect of nivolumab therapy [ 6 , 7 ], he was referred to the Neurology Department. However, based on the lack of both eye symptoms and clinically apparent muscle weakness in his extremities, and negative findings of anti-acetylcholine receptor antibody (AChRAb) (< 0.2 nmol/L, normal values: < 0.2 nmol/L), the neurologist determined that the patient did not have myasthenia gravis.…”

Section: Case Reportmentioning

confidence: 99%

Isolated Adrenocorticotropic Hormone Deficiency and Severe Hypercalcemia After Destructive Thyroiditis in a Patient on Nivolumab Therapy With a Malignant Melanoma

et al. 2018

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We describe a 58-year-old man with a malignant melanoma metastasis to the liver. After initiation of nivolumab therapy, he developed destructive thyroiditis and subsequently simultaneous isolated adrenocorticotropic hormone (ACTH) deficiency and severe hypercalcemia. Although isolated ACTH deficiency and hypercalcemia due to nivolumab therapy are both rare occurrences, these conditions can often cause a severe clinical course accompanied by a disturbance of consciousness. Therefore, clinicians should pay attention to these possible side effects of nivolumab if the patients have clinical symptoms, such as fatigue and a disturbance of consciousness.

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“…We found five cases had signs of other NMD; all had elevated CPK in the range 1156-6566 U/L, pointing to muscle involvement, and one had myopathic changes in the EMG 36 , while EMG data were not reported for the remaining four patients 25,32,40,47 (37%) of patient cases, authors were not affiliated with a neurological department).…”

Section: Myasthenia Gravismentioning

confidence: 85%

Neuromuscular Adverse Events Associated with Anti-PD-1 Monoclonal Antibodies: Systematic Review<strong> </strong>

Johansen¹,

Christensen²,

Scheie³

et al. 2018

Preprint

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Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. Using the PRISMA approach, we performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab. Sixty-three publications on 85 patients (mean age 66,9 years (range 34–86); male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3,6 (range 1–28). Symptoms included oculomotor (47%); respiratory (43%), bulbar (35%), and proximal weakness (35%); as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%) and a combination of these (16%). After critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 14% of patients had signs of additional NMDs. PD-1 inhibitor associated myasthenia was associated with cardiac complications in almost 30% of patients and with a more rapid clinical progression compared with idiopathic myasthenia. Mortality was high despite adequate treatment strategies including corticosteroid, IV immunoglobulins and plasmapheresis. In conclusion, clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with significant overlap between myasthenia gravis and myopathy; and cardiac/respiratory complications are common, leading to more severe disease courses than idiopathic myasthenia.

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Myasthenia Gravis Induced by Nivolumab in Patients with Non-Small-Cell Lung Cancer: A Case Report and Literature Review

Cited by 23 publications

References 30 publications

PD-1 Inhibitors-Related Neurological Toxicities in Patients with Non-Small-Cell Lung Cancer: A Literature Review

PD-1 Inhibitors-Related Neurological Toxicities in Patients with Non-Small-Cell Lung Cancer: A Literature Review

Isolated Adrenocorticotropic Hormone Deficiency and Severe Hypercalcemia After Destructive Thyroiditis in a Patient on Nivolumab Therapy With a Malignant Melanoma

Neuromuscular Adverse Events Associated with Anti-PD-1 Monoclonal Antibodies: Systematic Review<strong> </strong>

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