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July 2020; 7 (4) ArticleOpen Access

The Bruton tyrosine kinase inhibitor ibrutinib improves anti-MAG antibody polyneuropathy

Francesca Castellani, Andrea Visentin, Marta Campagnolo, Alessandro Salvalaggio, Mario Cacciavillani, Cinzia Candiotto, Roberta Bertorelle, View ORCID ProfileLivio Trentin, Chiara Briani
First published April 13, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000720
Francesca Castellani
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Andrea Visentin
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Marta Campagnolo
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Alessandro Salvalaggio
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Mario Cacciavillani
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Cinzia Candiotto
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Roberta Bertorelle
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Livio Trentin
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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  • ORCID record for Livio Trentin
Chiara Briani
From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
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Citation
The Bruton tyrosine kinase inhibitor ibrutinib improves anti-MAG antibody polyneuropathy
Francesca Castellani, Andrea Visentin, Marta Campagnolo, Alessandro Salvalaggio, Mario Cacciavillani, Cinzia Candiotto, Roberta Bertorelle, Livio Trentin, Chiara Briani
Neurol Neuroimmunol Neuroinflamm Jul 2020, 7 (4) e720; DOI: 10.1212/NXI.0000000000000720

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Abstract

Objective To assess whether neuropathy with anti-myelin-associated glycoprotein (MAG) antibody may improve after treatment with ibrutinib, an oral inhibitor of Bruton tyrosine kinase, we prospectively treated with ibrutinib a cohort of 3 patients with anti-MAG neuropathy and Waldenström macroglobulinemia (WM).

Methods All 3 patients underwent bone marrow biopsy showing WM, with MYD88L265P mutated and CXCR4S338X wild type, and were started on ibrutinib 420 mg/die. Patients were assessed at baseline, at 3-6-9 months, and at 12 months in 2 patients with a longer follow-up, using Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score, INCAT sensory sum score, and Medical Research Council sum score. The modified International Cooperative Ataxia Rating Scale was performed in 2 patients, whereas it was not used in the patient with Parkinson disease as a major comorbidity. Responders were considered the patients improving by at least one point in 2 clinical scales.

Results All the patients reported an early and subjective benefit, consistent with the objective improvement, especially of the sensory symptoms as shown by clinical scales. Treatment was well tolerated.

Conclusion These preliminary data point to a possible efficacy of ibrutinib in anti-MAG antibody neuropathy, which is the most common disabling paraproteinemic neuropathy, where active treatment is eagerly needed.

Classification of evidence This study provides Class IV evidence that for patients with anti-MAG antibody neuropathy, ibrutinib improves neuropathy symptoms.

Glossary

BMB=
bone marrow biopsy;
BTK=
Bruton tyrosine kinase;
IgM=
immunoglobulin M;
INCAT=
Inflammatory Neuropathy Cause and Treatment;
MAG=
myelin-associated glycoprotein;
MGUS=
monoclonal gammopathy of undetermined significance;
WM=
Waldenström macroglobulinemia

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • ↵* The authors share the first authorship.

  • The Article Processing Charge was funded by the authors.

  • Received December 23, 2019.
  • Accepted in final form March 12, 2020.
  • Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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