Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors

Moreira, Álvaro; Loquai, Carmen; Pföhler, Claudia; Kähler, Katharina C.; Knauß, Samuel; Heppt, Markus V.; Gutzmer, Ralf; Dimitriou, Florentia; Meier, Friedegund; Mitzel-Rink, Heidrun; Schuler, Gerold; Terheyden, Patrick; Thoms, Kai‐Martin; Türk, Matthias; Dummer, Reinhard; Zimmer, Lisa; Schröder, Rolf; Heinzerling, Lucie

doi:10.1016/j.ejca.2018.09.033

Cited by 196 publications

(199 citation statements)

References 53 publications

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“…Troponin‐I seems to be more specific than troponin‐T to suggest cardiac involvement . IrMyositis is typically antibody negative with some rare exceptions as the signal recognition particle antibodies that have been detected in isolated cases . One patient with irMyositis published in literature tested positive for anti‐striational antibodies, but these antibodies were also detected in a serum sample obtained prior to ICIs treatment, suggesting a pre‐existing subclinical autoreactivity …”

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

“…Myalgia was among the most common and early symptom, reported at presentation in approximately 2 out of 3 patients (Table ) and typically localized in the neck, back, or proximal limbs, often preceding the muscle weaknesses . Isolated myalgia without creatine kinase (CK) elevation has also been reported . Weakness may involve several muscular districts.…”

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

“…Progressive generalized muscle weakness and respiratory or cardiac muscle involvement represent the most prominent life‐threatening consequences of irMyositis but are detected only in a small proportion of patients. Ten percent to 20% of patients ultimately require non‐invasive or mechanical ventilation . Concurrent myocarditis is diagnosed in 25% to 35% of patients, being more frequent and severe in patients receiving ICIs combination .…”

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

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

Psimaras

Velasco

Birzu

et al. 2019

J Peripheral Nervous Sys

122

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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

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Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

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

Psimaras

Velasco

Birzu

et al. 2019

J Peripheral Nervous Sys

122

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“…Several neurologic prognoses have been reported after the discontinuation of ICIs . It is difficult to reconsider causative immunotherapy if myasthenia gravis improves, as there are insufficient data about the safety of reintroducing ICIs after recovery.…”

Section: Discussionmentioning

confidence: 99%

Myasthenia gravis and myopathy after nivolumab treatment for non‐small cell lung carcinoma: A case report

et al. 2019

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Here, we report a case of myasthenia gravis and myopathy in a patient treated with nivolumab. A 76‐year‐old man who had been treated with four doses of nivolumab because of non‐small cell lung cancer (NSCLC) presented with proximal‐dominant muscle weakness and fluctuating ptosis and diplopia. Serologic studies revealed increased levels of muscle enzymes including creatine phosphokinase (2934 U/L), and acetylcholine receptor antibody was positive (1.31 nmol/L). Following electrodiagnostic study, he was diagnosed with myasthenia gravis and active stage of myopathy. After discontinuation of nivolumab, he was treated with corticosteroids, intravenous immunoglobulin G, and pyridostigmine. The neuromuscular symptoms and serologic abnormalities of the patient markedly improved. Currently, he is taking oral steroids and pyridostigmine without further immunotherapy.

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“…It is important to be vigilant for occurrence of adverse effects of immunotherapy for cancer in patients with MG or underlying mild or latent MG (81)(82)(83). For example, treatment of patients with MG with ipilimumab (anti-CTLA4 mAb) for melanoma and lung cancer had fatal consequences (84).…”

Section: Perspectives: Advantages Limitations and Future Challengesmentioning

confidence: 99%

New Approaches to Targeting B Cells for Myasthenia Gravis Therapy

Huda

2020

Front. Immunol.

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Current therapies for myasthenia gravis (MG) are limited, and many investigations have recently focused on target-specific therapies. B cell-targeting monoclonal antibody (mAb) therapies for MG are increasingly attractive due to their specificity and efficacy. The targeted B cell biomarkers are mainly the cluster of differentiation (CD) proteins that mediate maturation, differentiation, or survival of pathogenic B cells. Additional B cell-directed therapies include non-specific peptide inhibitors that preferentially target specific B cell subsets. The primary goals of such therapies are to intercept autoantibodies and prevent the generation of an inflammatory response that contributes to the pathogenesis of MG. Treatment of patients with MG using B cell-directed mAbs, antibody fragments, or selective inhibitors have exhibited moderate to high efficacy in early studies, and some of these therapies appear to be highly promising for further drug development. Numerous other biologics targeting various B cell surface molecules have been approved for the treatment of other conditions or are either in clinical trials or preclinical development stages. These approaches remain to be tested in patients with MG or animal models of the disease. This review article provides an overview of B cell-targeted treatments for MG, including those already available and those still in preclinical and clinical development. We also discuss the potential benefits as well as the shortcomings of these approaches to development of new therapies for MG and future directions in the field.

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Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors

Cited by 196 publications

References 53 publications

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

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

Myasthenia gravis and myopathy after nivolumab treatment for non‐small cell lung carcinoma: A case report

New Approaches to Targeting B Cells for Myasthenia Gravis Therapy

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