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Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?

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 inhibi...

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Autores principales: Zaremba, Anne, Chorti, Eleftheria, Jockenhöfer, Finja, Bolz, Saskia, Sirin, Selma, Glas, Martin, Becker, Jürgen C., Ugurel, Selma, Roesch, Alexander, Schadendorf, Dirk, Livingstone, Elisabeth, Hagenacker, Tim, Zimmer, Lisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541996/
https://www.ncbi.nlm.nih.gov/pubmed/31142383
http://dx.doi.org/10.1186/s40425-019-0626-9
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author Zaremba, Anne
Chorti, Eleftheria
Jockenhöfer, Finja
Bolz, Saskia
Sirin, Selma
Glas, Martin
Becker, Jürgen C.
Ugurel, Selma
Roesch, Alexander
Schadendorf, Dirk
Livingstone, Elisabeth
Hagenacker, Tim
Zimmer, Lisa
author_facet Zaremba, Anne
Chorti, Eleftheria
Jockenhöfer, Finja
Bolz, Saskia
Sirin, Selma
Glas, Martin
Becker, Jürgen C.
Ugurel, Selma
Roesch, Alexander
Schadendorf, Dirk
Livingstone, Elisabeth
Hagenacker, Tim
Zimmer, Lisa
author_sort Zaremba, Anne
collection PubMed
description 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.
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spelling pubmed-65419962019-06-03 Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors? Zaremba, Anne Chorti, Eleftheria Jockenhöfer, Finja Bolz, Saskia Sirin, Selma Glas, Martin Becker, Jürgen C. Ugurel, Selma Roesch, Alexander Schadendorf, Dirk Livingstone, Elisabeth Hagenacker, Tim Zimmer, Lisa J Immunother Cancer Case Report 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. BioMed Central 2019-05-29 /pmc/articles/PMC6541996/ /pubmed/31142383 http://dx.doi.org/10.1186/s40425-019-0626-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Zaremba, Anne
Chorti, Eleftheria
Jockenhöfer, Finja
Bolz, Saskia
Sirin, Selma
Glas, Martin
Becker, Jürgen C.
Ugurel, Selma
Roesch, Alexander
Schadendorf, Dirk
Livingstone, Elisabeth
Hagenacker, Tim
Zimmer, Lisa
Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?
title 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_short 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?
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541996/
https://www.ncbi.nlm.nih.gov/pubmed/31142383
http://dx.doi.org/10.1186/s40425-019-0626-9
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