Neurotoxicity and safety of the rechallenge of immune checkpoint inhibitors: a growing issue in neuro-oncology practice

Villagrán-García, Macarena; Velasco, Roser

doi:10.1007/s10072-022-05920-4

Cited by 27 publications

(31 citation statements)

References 149 publications

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“…[ 71 , 72 ] are common irAE caused by the blockade of PD1/PD-L1 pathways and/or CTLA4 ( Table 1 ) [ 61 ]. Although the guidelines for the management of these irAEs described above are well established [ 61 ], severe irAEs of these organs, as well as minor irAEs such as neurotoxicity [ 73 , 74 ], ocular disorders [ 75 , 76 ], muscle skeletal disorders [ 77 , 78 ] and cardiovascular disorders [ 79 ], are still major problems with the use of ICIs. Importantly, the onset of these irAEs was correlated with increased serum levels of CXCL5 [ 72 , 78 , 80 ], a well-known biomarker for the activity of autoimmune disorders such as rheumatoid arthritis [ 81 , 82 ].…”

Section: Adverse Events Of Icismentioning

confidence: 99%

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Fujimura

Muto

Asano

2022

IJMS

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Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted mainly of cytotoxic agents such as dacarbazine and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have been recognized as anchor drugs for treating advanced melanoma, with or without additional combination drugs such as ipilimumab, but the efficacies of these immunotherapies are not fully satisfactory. In this review, we describe the development of the currently available anti-PD1 Abs-based immunotherapies for advanced melanoma, focusing on their efficacy and immune-related adverse events (AEs), as well as clinical trials still ongoing for the future treatment of advanced melanoma.

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Section: Adverse Events Of Icismentioning

confidence: 99%

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Fujimura

Muto

Asano

2022

IJMS

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“…Neurological immune related adverse events (nrl-irAEs) are uncommon presenting an estimated overall incidence of 7.2% [9]; with severe forms occurring in up to 3% of patients receiving ICIs [10]. Nrl-irAEs include a wide spectrum of manifestations involving the entire neuroaxis, i.e., muscle, neuromuscular junction, peripheral nerve and central nervous system (CNS) [11][12][13]. Neuromuscular disorders are more frequent and have an earlier presentation than those involving the CNS [3,12].…”

Section: Introductionmentioning

confidence: 99%

“…Immune-related myasthenia gravis (irMG) can occur as an exacerbation of pre-existing MG or de novo in patients with no previous MG diagnosis. The clinical picture is usually characterized by progressive weakness affecting the extraocular, bulbar and limb muscles, progressing to respiratory failure in 40-65% of reported cases [13]. Some patients have mild symptoms such as ptosis while other patients may present with rapidly progressive respiratory failure with fatal outcome [15].…”

Section: Introductionmentioning

confidence: 99%

“…The presence of myositis and myocarditis overlapping irMG is a very common association. This syndrome, also named "3M triad", is especially challenging and life-threatening [13,[15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…An approach involving experienced neurologists in specialized multidisciplinary care teams is of great importance in the management of these patients [13,18]. In the present retrospective case-series study, we describe our experience in an oncologic center with six patients diagnosed of irMG due to ICI.…”

Section: Introductionmentioning

confidence: 99%

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

Marco

Simó

Alemany

et al. 2022

JCM

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Immunotherapy with immune checkpoint inhibitors (ICIs) have been reported to induce de novo or exacerbate pre-existing Myasthenia Gravis (MG). We present a single center case series of patients who developed an immune-related myasthenia gravis (irMG) related with ICIs. We performed a retrospective chart review of the electronic medical records between 1 September 2017 and 2022. We report the clinical features, presentation forms, diagnostic workflows, general management and outcomes of six patients who received ICIs for different solid organ malignancies and developed an irMG frequently overlapping with immune-related myocarditis and/or myositis. The aim of the article is to describe the clinical features, treatment and outcomes of this challenging and potentially life-threating syndrome, comparing our data with those described in the literature. Differences between irMG and classic MG are highlighted.

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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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Neurotoxicity and safety of the rechallenge of immune checkpoint inhibitors: a growing issue in neuro-oncology practice

Cited by 27 publications

References 149 publications

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

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

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

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