Lambert-Eaton Myasthenic Syndrome Caused by Nivolumab in a Patient with Squamous Cell Lung Cancer

Nakatani, Yuki; Tanaka, Natsuki; Enami, Tomomi; Minami, Seigo; Okazaki, Toshio; Komuta, Kiyoshi

doi:10.1159/000494078

Cited by 70 publications

(51 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our literature search, we also found one case of LEMS in a patient with squamous cell lung cancer which was attributed to ICI [14]. In this case, the patient had squamous cell lung cancer which is less commonly associated with LEMS.…”

Section: Discussionmentioning

confidence: 96%

Lambert-Eaton Myasthenic Syndrome Secondary to Nivolumab and Ipilimumab in a Patient with Small-Cell Lung Cancer

Agrawal

2019

Case Reports in Neurological Medicine

View full text Add to dashboard Cite

We present a case of a 59-year-old male with a confirmed diagnosis of small-cell lung cancer (SCLC). He had progressive disease even after four cycles of cisplatin and etoposide chemotherapy and 21 cycles of radiation. He was therefore started on immunotherapy with nivolumab every 2 weeks and ipilimumab every 6 weeks. After 4 months of starting immunotherapy, he reported extreme fatigue, muscular weakness, and poor appetite. He was diagnosed with hypothyroidism, primary adrenal insufficiency, and Lambert-Eaton Myasthenic Syndrome (LEMS). LEMS can be both a paraneoplastic syndrome of SCLC and an adverse effect of immunotherapy. Currently, there is no diagnostic test available to determine if a case of LEMS is a paraneoplastic syndrome or immunotherapy-related adverse effect. In our patient, we felt that LEMS was an immunotherapy-related adverse effect rather being a paraneoplastic syndrome. Our determination was based on the time of onset of muscular weakness, presence of other immunotherapy-mediated adverse events, and the appearance of symptoms in spite of SCLC that had been stabilized on immunotherapy. Accordingly, immunotherapy was stopped and a brief tapering course of steroids was initiated. Our patient’s muscular weakness from LEMS responded well. His clinical improvement persisted even with radiologic progression of disease after cessation of immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 96%

Lambert-Eaton Myasthenic Syndrome Secondary to Nivolumab and Ipilimumab in a Patient with Small-Cell Lung Cancer

Agrawal

2019

Case Reports in Neurological Medicine

View full text Add to dashboard Cite

show abstract

“…Other studies have reported detection of Ma2 IgG (n = 6) among CNS irAE with variable cancer subtypes, not compatible with typical oncological association (germ cell tumors) of Ma2 IgG . As indications for cancer immunotherapies grow, cases of classic paraneoplastic phenotypes are also reported; for example, limbic encephalitis in association with anti‐Hu, antineuronal nuclear antibody type‐1, and Lambert–Eaton myasthenia syndrome in association with P/Q type voltage gated calcium channel antibodies . It is possible that the proportion of cases with classic paraneoplastic phenotypes in association with specific malignancies such as small cell cancer may become more apparent .…”

Section: Atypical Overlapping Spectrum Of Irae‐nmentioning

confidence: 98%

Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum

Dubey

David

Reynolds

et al. 2020

Annals of Neurology

174

189

View full text Add to dashboard Cite

Expanding use of immune-checkpoint inhibitors (ICIs) underscores the importance of accurate diagnosis and timely management of neurological immune-related adverse events (irAE-N). We evaluate the real-world frequency, phenotypes, co-occurring immune-related adverse events (irAEs), and long-term outcomes of severe, grade III to V irAE-N at a tertiary care center over 6 years. We analyze how our experience supports published literature and professional society guidelines. We also discuss these data with regard to common clinical scenarios, such as combination therapy, ICI rechallenge and risk of relapse of irAE-N, and corticosteroid taper, which are not specifically addressed by current guidelines and/or have limited data. Recommendations for management and future irAE-N reporting are outlined.

show abstract

“…Except a case of pre‐synaptic Lambert‐Eaton myasthenic syndrome, only cases of post‐synaptic irMG have been described. Impairment of neuromuscular transmission on electrodiagnostic tests is not often reported.…”

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

“…Therefore, a thorough evaluation should be conducted each time a pns‐irAEs is evoked, including CK and troponins dosage, as the risk of overlapping myocarditis is significant . Testing for onconeural and organ‐specific autoantibodies should be performed based on presenting clinical phenotype: anti‐AChR, anti‐MuSK, anti‐Ca ++ channel and striatational antibodies in patients with suspected irMG, systemic autoimmunity (ANA, dsDNA, anti‐SNA, and ANCA) and anti‐ganglioside antibodies in patients with peripheral neuropathies, and myositis‐associated antibodies in patients with suspected irMyositis . The suspicion of a neuromuscular disease should automatically impose distal and proximal NCS and ENMG of all four limbs.…”

Section: Management Of Peripheral Nervous System Immune‐related Advermentioning

confidence: 99%

Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

Psimaras

Velasco

Birzu

et al. 2019

J Peripheral Nervous Sys

122

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) are increasingly used and are becoming the standard of care in the treatment of various tumor types. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events (irAEs). Neurological irAEs are rare but potentially severe. Neuromuscular disorders represent the most common neurological irAEs following anti-PD-1, anti-PD-L1, and anti-CTLA-4 treatment, and include myositis, myasthenia gravis, and demyelinating polyradiculoneuropathy. Instrumental findings may differ from typical neuromuscular disorders occurring outside ICIs treatment.Despite initial severity, neurological irAEs often respond to immune-modulating therapies. Prompt irAEs diagnosis, ICIs discontinuation, and early treatment with corticosteroids, together with patient education and a multi-disciplinary approach, are important for optimizing clinical outcomes. Intravenous immunoglobulin, plasma exchange, and other immune-modulating treatments should be considered in more severe cases. Consideration of re-challenging with the same immunotherapy drug may be given in some cases, based on clinical picture and initial severity of irAEs. K E Y W O R D SCTLA-4, demyelinating polyradiculoneuropathy, immune checkpoint inhibitor, myasthenia gravis, myositis, nivolumab, PD-1, PD-L1, pembrolizumab, peripheral neuropathy

show abstract

Lambert-Eaton Myasthenic Syndrome Caused by Nivolumab in a Patient with Squamous Cell Lung Cancer

Cited by 70 publications

References 15 publications

Lambert-Eaton Myasthenic Syndrome Secondary to Nivolumab and Ipilimumab in a Patient with Small-Cell Lung Cancer

Lambert-Eaton Myasthenic Syndrome Secondary to Nivolumab and Ipilimumab in a Patient with Small-Cell Lung Cancer

Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum

Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

Contact Info

Product

Resources

About