Myasthenia gravis associated with ipilimumab and nivolumab in the treatment of small cell lung cancer

Loochtan, Aaron I.; Nickolich, Myles; Hobson‐Webb, Lisa D.

doi:10.1002/mus.24648

Cited by 97 publications

(45 citation statements)

References 11 publications

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“…The functional burden caused by the development of MG contributed to the death of 1 patient, whereas the other patient improved after plasmapheresis. In lung cancer, MG symptoms were reported after combination therapy with either PD‐1 or PD‐L1 and CTLA‐4 inhibitors . In these particular cases, the patients developed complications associated with MG exacerbation and did not survive.…”

Section: Mg Induction; a Side Effect Of Cancer Immunotherapymentioning

confidence: 99%

B cells in the pathophysiology of myasthenia gravis

et al. 2017

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Myasthenia gravis (MG) is an archetypal autoimmune disease. The pathology is characterized by autoantibodies to the acetylcholine receptor (AChR) in most patients or to muscle-specific tyrosine kinase (MuSK) in others and to a growing number of other postsynaptic proteins in smaller subsets. A decrease in the number of functional AChRs or functional interruption of the AChR within the muscle end plate of the neuromuscular junction is caused by pathogenic autoantibodies. Although the molecular immunology underpinning the pathology is well understood, much remains to be learned about the cellular immunology contributing to the production of autoantibodies. This Review documents research concerning the immunopathology of MG, bringing together evidence principally from human studies with an emphasis on the role of adaptive immunity and B cells in particular. Proposed mechanisms for autoimmunity, which take into account that different types of MG may incorporate divergent immunopathology, are offered. Muscle Nerve 57: 172-184, 2018.

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Section: Mg Induction; a Side Effect Of Cancer Immunotherapymentioning

confidence: 99%

B cells in the pathophysiology of myasthenia gravis

et al. 2017

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“…New-onset type I diabetes mellitus has been reported in at least 1 instance in a patient with cHL treated with nivolumab 84. While rare and not yet reported in patients with cHL treated with nivolumab, it is worthwhile for the clinician to be aware of the potential for life-threatening myocarditis, rhabdomyolysis, neurologic disorders including myasthenia gravis and Guillain-Barré syndrome, and skin reactions including Stevens–Johnson syndrome, bullous pemphigoid, and toxic epidermal necrolysis, which have been seen in patients following checkpoint blockade 80,82,85–88. Despite the side effects associated with PD-1 blockade, nivolumab is relatively well tolerated overall and generally associated with fewer high-grade side effects when compared with conventional chemotherapy 89…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of Nivolumab

Bond

Alinari

2017

JBM

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Classical Hodgkin’s lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell. Enhancing antitumor immune response by targeting PD-1 with the monoclonal antibody nivolumab has proved to be effective in multiple solid tumors, but the highest response rates to date have been reported in patients with cHL, with over 65% of treated patients achieving an objective clinical response. In this review, we will summarize the published evidence regarding the activity of nivolumab in cHL as well as its current place in therapy. We will review the pharmacology, mechanism of action, and side effects of nivolumab as well as the emerging data indicating possible increased risk of graft versus host disease in patients treated with PD-1 inhibitors either pre- or post-allogeneic stem cell transplant. Given the remarkable single-agent activity and safety profile of PD-1 inhibitors in heavily pretreated patients with cHL, the possibility of employing nivolumab in combination with other active agents and earlier in therapy is a promising area of active investigation, and we will briefly summarize current clinical trials.

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“…Despite their clinical benefits, these antibodies induce various kinds of immune-related adverse events (5). Most recently, myasthenia gravis (MG) has been reported after treatment with Ipi and the combination of Ipi and Nivo (6,7). Although the exact mechanism underlying MG induction is unclear, in vivo and in vitro findings suggest that Ipi may play a causal role.…”

Section: Introductionmentioning

confidence: 99%

Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma

Shirai

Sano

Kamijo

et al. 2015

Jpn. J. Clin. Oncol.

128

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We reported an 81-year-old woman with metastatic melanoma, in whom myasthenia gravis and rhabdomyolysis developed after nivolumab monotherapy. The first symptom of myasthenia gravis was dyspnea. Ultrasonography detected hypokinesis of the bilateral diaphragm suggesting myasthenia gravis, although there was no abnormal finding of the lungs in computed tomography images. Acetylcholine receptor binding antibodies were low-titer positive in the preserved serum before administration of nivolumab, strongly suggesting that the myasthenia gravis was a nivolumab-related immune adverse event. Despite the remarkable clinical benefits of immune checkpoint inhibitors for patients with advanced melanoma, it is important to recognize unexpected immunerelated adverse events.

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Myasthenia gravis associated with ipilimumab and nivolumab in the treatment of small cell lung cancer

Cited by 97 publications

References 11 publications

B cells in the pathophysiology of myasthenia gravis

B cells in the pathophysiology of myasthenia gravis

Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of Nivolumab

Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma

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Myasthenia gravis associated with ipilimumab and nivolumab in the treatment of small cell lung cancer

Cited by 97 publications

References 11 publications

B cells in the pathophysiology of myasthenia gravis

B cells in the pathophysiology of myasthenia gravis

Emerging treatment options for the management of Hodgkin&#39;s lymphoma: clinical utility of Nivolumab

Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma

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Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of Nivolumab