Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?
Abstract Background PD-1/PD-L1 inhibitors are promising approaches for advanced Merkel cell carcinoma (MCC). Nevertheless, these inhibitors bear a high risk for induction of immune-related adverse events (irAEs), particularly flares of preexisting autoimmune diseases. Neurological irAEs of PD-1/PD-L...
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doaj-863ee486a7f24d20ad7d0dbaff912dd42020-11-25T00:46:34ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262019-05-01711610.1186/s40425-019-0626-9Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?Anne Zaremba0Eleftheria Chorti1Finja Jockenhöfer2Saskia Bolz3Selma Sirin4Martin Glas5Jürgen C. Becker6Selma Ugurel7Alexander Roesch8Dirk Schadendorf9Elisabeth Livingstone10Tim Hagenacker11Lisa Zimmer12Department of Dermatology, University Hospital EssenDepartment of Dermatology, University Hospital EssenDepartment of Dermatology, University Hospital EssenDepartment of Neurology, University Hospital EssenDepartment of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital EssenDivision of Clinical Neurooncology, Department of Neurology, University Hospital EssenDepartment of Dermatology, University Hospital EssenDepartment of Dermatology, University Hospital EssenDepartment of Dermatology, University Hospital EssenDepartment of Dermatology, University Hospital EssenDepartment of Dermatology, University Hospital EssenDepartment of Neurology, University Hospital EssenDepartment of Dermatology, University Hospital EssenAbstract Background PD-1/PD-L1 inhibitors are promising approaches for advanced Merkel cell carcinoma (MCC). Nevertheless, these inhibitors bear a high risk for induction of immune-related adverse events (irAEs), particularly flares of preexisting autoimmune diseases. Neurological irAEs of PD-1/PD-L1 inhibitors are possibly underestimated and potentially fatal toxicities. Additionally, exacerbations of preexisting myasthenia gravis (MG) with a high MG-specific-related mortality have been reported. Case presentation A 61-year-old woman with a history of MG since 2005 was treated with azathioprine and pyridostigmine after thymectomy. In March 2016, she was diagnosed with MCC. Six months later the tumor had progressed to stage IV and metastases were detected in lymph nodes and the pancreas. The immunosuppressive therapy was therefore changed to mycophenolatmofetil (MMF) and an immune checkpoint blockade with the PD-1 inhibitor pembrolizumab was initiated in November 2016. Due to MMF-induced liver toxicity, MMF was switched to cyclosporine A (CsA) with normalized liver transaminases six weeks later. After six cycles of pembrolizumab the patient achieved a partial response. Follow up analysis sixty-five weeks later revealed a long-lasting tumor response with a partial remission of pancreatic and inguinal metastases and no flare of MG. Conclusions Patients with a preexisting MG can be considered for treatment with immune checkpoint inhibitors if they have a life-threatening cancer and if other effective, long-lasting treatment options are not available. The risks and benefits of therapy should be weighed in a multidisciplinary setting and should be discussed thoroughly with the patient. Exacerbation of underlying MG can be potentially life-threatening and requires close monitoring in collaboration with neuromuscular specialists.http://link.springer.com/article/10.1186/s40425-019-0626-9Merkel cell carcinomaMyasthenia gravisImmune checkpoint inhibitorAdverse eventsImmunotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anne Zaremba Eleftheria Chorti Finja Jockenhöfer Saskia Bolz Selma Sirin Martin Glas Jürgen C. Becker Selma Ugurel Alexander Roesch Dirk Schadendorf Elisabeth Livingstone Tim Hagenacker Lisa Zimmer |
spellingShingle |
Anne Zaremba Eleftheria Chorti Finja Jockenhöfer Saskia Bolz Selma Sirin Martin Glas Jürgen C. Becker Selma Ugurel Alexander Roesch Dirk Schadendorf Elisabeth Livingstone Tim Hagenacker Lisa Zimmer Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? Journal for ImmunoTherapy of Cancer Merkel cell carcinoma Myasthenia gravis Immune checkpoint inhibitor Adverse events Immunotherapy |
author_facet |
Anne Zaremba Eleftheria Chorti Finja Jockenhöfer Saskia Bolz Selma Sirin Martin Glas Jürgen C. Becker Selma Ugurel Alexander Roesch Dirk Schadendorf Elisabeth Livingstone Tim Hagenacker Lisa Zimmer |
author_sort |
Anne Zaremba |
title |
Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? |
title_short |
Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? |
title_full |
Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? |
title_fullStr |
Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? |
title_full_unstemmed |
Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? |
title_sort |
metastatic merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2019-05-01 |
description |
Abstract Background PD-1/PD-L1 inhibitors are promising approaches for advanced Merkel cell carcinoma (MCC). Nevertheless, these inhibitors bear a high risk for induction of immune-related adverse events (irAEs), particularly flares of preexisting autoimmune diseases. Neurological irAEs of PD-1/PD-L1 inhibitors are possibly underestimated and potentially fatal toxicities. Additionally, exacerbations of preexisting myasthenia gravis (MG) with a high MG-specific-related mortality have been reported. Case presentation A 61-year-old woman with a history of MG since 2005 was treated with azathioprine and pyridostigmine after thymectomy. In March 2016, she was diagnosed with MCC. Six months later the tumor had progressed to stage IV and metastases were detected in lymph nodes and the pancreas. The immunosuppressive therapy was therefore changed to mycophenolatmofetil (MMF) and an immune checkpoint blockade with the PD-1 inhibitor pembrolizumab was initiated in November 2016. Due to MMF-induced liver toxicity, MMF was switched to cyclosporine A (CsA) with normalized liver transaminases six weeks later. After six cycles of pembrolizumab the patient achieved a partial response. Follow up analysis sixty-five weeks later revealed a long-lasting tumor response with a partial remission of pancreatic and inguinal metastases and no flare of MG. Conclusions Patients with a preexisting MG can be considered for treatment with immune checkpoint inhibitors if they have a life-threatening cancer and if other effective, long-lasting treatment options are not available. The risks and benefits of therapy should be weighed in a multidisciplinary setting and should be discussed thoroughly with the patient. Exacerbation of underlying MG can be potentially life-threatening and requires close monitoring in collaboration with neuromuscular specialists. |
topic |
Merkel cell carcinoma Myasthenia gravis Immune checkpoint inhibitor Adverse events Immunotherapy |
url |
http://link.springer.com/article/10.1186/s40425-019-0626-9 |
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