Myasthenia Gravis Induced by Immune Checkpoint Inhibitors: An Emerging Neurotoxicity in Neuro-Oncology Practice: Case Series

Marco, Carla; Simó, Marta; Alemany, M.; Casasnovas, Carlos; Domínguez, Raúl; Calvo, Mariona; Martín-Liberal, Juan; Brenes, J.; Sabater-Riera, Joan; Bruna, Jordi; Velasco, Roser

doi:10.3390/jcm12010130

Cited by 11 publications

(6 citation statements)

References 38 publications

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“…98 The neuromuscular phenotype of immune checkpoint inhibitor toxicity may be more prevalent with anti-PD-1/PD-L1 therapy. 99 Moreover, the overlap of myositis with myasthenia is more commonly seen in this population, 96,99 which can contribute to higher fatality rates seen with this presentation, attributed to refractory neuromuscular respiratory failure.…”

Section: Commentmentioning

confidence: 99%

“…Patients with extralimbic meningoencephalitis or with focal limbic involvement with either no autoantibody or positive anti–glutamic acid decarboxylase or anti–cell-surface antibodies are more likely to respond to therapy and achieve a favorable outcome 98 . The neuromuscular phenotype of immune checkpoint inhibitor toxicity may be more prevalent with anti-PD-1/PD-L1 therapy 99 . Moreover, the overlap of myositis with myasthenia is more commonly seen in this population, 96,99 which can contribute to higher fatality rates seen with this presentation, attributed to refractory neuromuscular respiratory failure.…”

Section: Treatment-related Complicationsmentioning

confidence: 99%

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Neuro-oncologic Emergencies

Maciel,

Busl

2024

CONTINUUM: Lifelong Learning in Neurology

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OBJECTIVE Neuro-oncologic emergencies have become more frequent as cancer remains one of the leading causes of death in the United States, second only to heart disease. This article highlights key aspects of epidemiology, diagnosis, and management of acute neurologic complications in primary central nervous system malignancies and systemic cancer, following three thematic classifications: (1) complications that are anatomically or intrinsically tumor-related, (2) complications that are tumor-mediated, and (3) complications that are treatment-related. LATEST DEVELOPMENTS The main driver of mortality in patients with brain metastasis is systemic disease progression; however, intracranial hypertension, treatment-resistant seizures, and overall decline due to increased intracranial burden of disease are the main factors underlying neurologic-related deaths. Advances in the understanding of tumor-specific characteristics can better inform risk stratification of neurologic complications. Following standardized grading and management algorithms for neurotoxic syndromes related to newer immunologic therapies is paramount to achieving favorable outcomes. ESSENTIAL POINTS Neuro-oncologic emergencies span the boundaries of subspecialties in neurology and require a broad understanding of neuroimmunology, neuronal hyperexcitability, CSF flow dynamics, intracranial compliance, and neuroanatomy.

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Section: Commentmentioning

confidence: 99%

Section: Treatment-related Complicationsmentioning

confidence: 99%

Neuro-oncologic Emergencies

Maciel,

Busl

2024

CONTINUUM: Lifelong Learning in Neurology

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“…ICI-related Myasthenia Gravis usually differs from classical forms because of frequent bulbar and respiratory involvement, which occur in more than half of patients [159,166,167]. By contrast, isolated ocular forms are uncommon.…”

Section: Neurological Iraesmentioning

confidence: 99%

Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations

Casagrande,

Sopetto,

Bertalot

et al. 2024

Cancers

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The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness.

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“…It is rapidly progressive, with frequent crisis; mortality is high (30%-40%) and increases with concurrent myositis or myocarditis (35%-60%). [5][6][7][8][9] Treatments include corticosteroids, intravenous immunoglobulin, plasma exchange (PLEX), and rituximab. 10 Two patients with ICI-MG responding to efgartigimod and one to eculizumab have been reported.…”

Section: Introductionmentioning

confidence: 99%

“…ICI‐induced MG (ICI‐MG) is frequently associated with myositis (≈50%) and/or myocarditis (≈18%). It is rapidly progressive, with frequent crisis; mortality is high (30%–40%) and increases with concurrent myositis or myocarditis (35%–60%) 5–9 . Treatments include corticosteroids, intravenous immunoglobulin, plasma exchange (PLEX), and rituximab 10 .…”

Section: Introductionmentioning

confidence: 99%

Novel uses of complement inhibitors in myasthenia gravis—Two case reports

Zadeh,

Price,

Drews

et al. 2024

Muscle and Nerve

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Introduction/AimsMyasthenia gravis (MG) is a rare, life‐threatening immune‐related adverse effect (irAE) of immune checkpoint inhibitor (ICI) treatment. C5‐complement inhibitors are effective treatments for acetylcholine receptor antibody (AChR ab) positive generalized MG. We describe the use of eculizumab/ravulizumab in two patients with MG receiving concomitant pembrolizumab.MethodsThis was a retrospective review of two medical records.ResultsPatient 1: An 80‐year‐old male with recurrent, non‐muscle invasive transitional cell carcinoma of the bladder developed ICI‐induced AChR ab positive MG (ICI‐MG), myositis, and myocarditis 2 weeks after the first dose of pembrolizumab. Myositis responded to corticosteroids. MG responded to eculizumab, followed by ravulizumab. He died of metastatic cancer 8 months later. Patient 2: A 58‐year‐old male had refractory thymoma‐associated AChR ab‐positive MG, which responded to eculizumab. He developed metastatic Merkel cell cancer necessitating pembrolizumab. MG remained stable on eculizumab. He had no irAEs for 22 months, with positron emission tomographic resolution of cancer. He then developed mild, indolent retinal vasculitis, which responded to prednisone. Discontinuation of pembrolizumab for 5 months resulted in cancer recurrence; pembrolizumab was resumed with peri‐infusion pulse prednisone. MG remained stable and he continues eculizumab.DiscussionIn the first patient, eculizumab, followed by ravulizumab, improved ICI‐MG. In the second patient, eculizumab treatment may have had a prophylactic effect on the development of ICI‐induced irAEs. The effect of complement inhibition on cancer outcomes of ICI therapy is unknown. A possible biologic basis for complement inhibitors in reducing irAEs of ICI, especially in the presence of underlying autoimmune disease, merits evaluation.

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Myasthenia Gravis Induced by Immune Checkpoint Inhibitors: An Emerging Neurotoxicity in Neuro-Oncology Practice: Case Series

Cited by 11 publications

References 38 publications

Neuro-oncologic Emergencies

Neuro-oncologic Emergencies

Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations

Novel uses of complement inhibitors in myasthenia gravis—Two case reports

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