Nivolumab‐associated <scp>Lambert‐Eaton</scp> myasthenic syndrome and cerebellar dysfunction in a patient with a neuroendocrine tumor

Gill, Alexander J.; Gandhy, Shruti U.; Lancaster, Eric

doi:10.1002/mus.27141

Cited by 22 publications

(16 citation statements)

References 10 publications

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“…Due to the paucity of cases of ICI-related LEMS, it remains unclear if ICI-related LEMS will be highly responsive to 3,4 DAP without the need for other adjunctive immunosuppressive therapy (as is typical for paraneoplastic LEMS), or if they will behave more like other ICI-related neuromuscular toxicities and require steroids and/or addition immunosuppressive therapies. Notably, in the two previous case reports of irAE LEMS, the response to steroids was limited, counter to most irAEs and one patient who failed IVIG therapy required rituximab [17,18]. Although the numbers are very small it does raise some questions about the pathophysiology of irAEs LEMS and consequently the optimal management of resilient immunemediated LEMS.…”

Section: Discussionmentioning

confidence: 95%

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Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Anderson¹,

Guidon²,

Khan³

et al. 2021

OBM Neurobiology

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Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder involving loss of functional pre-synaptic P/Q-type voltage-gated calcium channels. Many cases occur as a paraneoplastic disorder, often in small cell lung cancer (SCLC). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). Here, we explore therapeutic and diagnostic conundrums from the unclear etiology (paraneoplastic vs. irAE) of a case of LEMS in a patient with SCLC treated with ICI therapy. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

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Section: Discussionmentioning

confidence: 95%

“…There are limited reports of ICI-related LEMS and no consensus on optimal treatment [4,17,18]. In general, management of neuromuscular irAEs depends on symptom severity [19].…”

Section: Discussionmentioning

confidence: 99%

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Anderson¹,

Guidon²,

Khan³

et al. 2021

OBM Neurobiology

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“…Rarely, LEMS has been reported as an adverse event of cancer treatment in patients receiving immune checkpoint inhibitors therapy [73][74][75][76][77]. These are a group of monoclonal antibodies directed against immune cell receptors expressed on T cells or their ligand, which aim at boosting the anti-tumor activity of cytotoxic T cells by interfering with inhibiting signals that reduce their activity [78].…”

Section: Cancer Associationmentioning

confidence: 99%

“…Immune-related adverse events (irAE) have been observed with every class of ICI and are related to the promotion of cellular-and antibody-mediated autoimmunity, although the exact underlying pathophysiological mechanisms remains only partially understood and several factors may play a role [79]. LEMS has been reported after treatment with different ICI (nivolumab, pembrolizumab, and ipilimumab) for different cancers, including SCLC [73,75,77], squamous cell lung carcinoma [74], and neuroendocrine tumor [76]. Response to immunotherapy, 3,4-diaminopyridine (3,4-DAP), and ICI withdrawal were variable.…”

Section: Cancer Associationmentioning

confidence: 99%

Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021

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The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

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“…However, a case of LEMS associated with ICI use was extremely rare in our literature review. To our knowledge, there have been four case reports of ICIs associated with LEMS in patients with lung cancer (5)(6)(7)(8). In three of these case reports, nivolumab was used, and one of them was in combination with ipilimumab.…”

Section: Discussionmentioning

confidence: 99%

Lambert-Eaton Myasthenic Syndrome Caused by Atezolizumab in a Patient with Small-cell Lung Cancer

et al. 2022

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We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.

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Nivolumab‐associated Lambert‐Eaton myasthenic syndrome and cerebellar dysfunction in a patient with a neuroendocrine tumor

Cited by 22 publications

References 10 publications

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

Lambert-Eaton Myasthenic Syndrome Caused by Atezolizumab in a Patient with Small-cell Lung Cancer

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