Obinutuzumab, a new anti-CD20 antibody, and chlorambucil are active and effective in anti-myelin-associated glycoprotein antibody polyneuropathy.


Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
02 2019
Historique:
received: 15 06 2018
accepted: 08 10 2018
pubmed: 14 10 2018
medline: 25 6 2019
entrez: 14 10 2018
Statut: ppublish

Résumé

Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used in polyneuropathy associated with anti-myelin-associated glycoprotein (anti-MAG) antibody polyneuropathy with controversial results. Herein, two patients with anti-MAG antibody neuropathy and concurrent chronic lymphocytic leukemia (CLL) are reported, who dramatically responded to obinutuzumab, a novel glycoengineered humanized anti-CD20 monoclonal antibody. Patient 1 was an 82-year-old man with severe demyelinating sensory-motor neuropathy. He was wheelchair-bound, with loss of sensation up to the knees. He had a CLL, immunoglobulin M (IgM) lambda monoclonal gammopathy, with anti-MAG antibodies >70 000 Bühlmann titer units (BTU). Patient 2 was an 84-year-old woman with demyelinating neuropathy, paresthesias and gait instability. She had CLL and IgM kappa paraprotein with anti-MAG antibodies >70 000 BTU. Both patients were treated with obinutuzumab intravenously at 100 mg on day +1, 900 mg +2, then at 1000 mg on days 8 and 15 of cycle 1 and day 1 of cycles 2-6; chlorambucil was given orally at 0.5 mg/kg on days 1 and 15 of cycles 1-6. Patient 1 at cycle 6 was able to stand, gait was possible with monolateral support, hypoesthesia and strength improved. M-protein and IgM level decreased. In patient 2, already after three cycles, the monoclonal component disappeared and there was dramatic improvement of symptoms and gait normalization. At the end of therapy anti-MAG antibody titer decreased to 5462 BTU. Neurophysiology also improved. In our patients, obinutuzumab was effective as a first-line treatment of anti-MAG antibody polyneuropathy. CLL might have had a role in the response to therapy, but the associations might be considered in future trials.

Sections du résumé

BACKGROUND AND PURPOSE
Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used in polyneuropathy associated with anti-myelin-associated glycoprotein (anti-MAG) antibody polyneuropathy with controversial results. Herein, two patients with anti-MAG antibody neuropathy and concurrent chronic lymphocytic leukemia (CLL) are reported, who dramatically responded to obinutuzumab, a novel glycoengineered humanized anti-CD20 monoclonal antibody.
METHODS
Patient 1 was an 82-year-old man with severe demyelinating sensory-motor neuropathy. He was wheelchair-bound, with loss of sensation up to the knees. He had a CLL, immunoglobulin M (IgM) lambda monoclonal gammopathy, with anti-MAG antibodies >70 000 Bühlmann titer units (BTU). Patient 2 was an 84-year-old woman with demyelinating neuropathy, paresthesias and gait instability. She had CLL and IgM kappa paraprotein with anti-MAG antibodies >70 000 BTU. Both patients were treated with obinutuzumab intravenously at 100 mg on day +1, 900 mg +2, then at 1000 mg on days 8 and 15 of cycle 1 and day 1 of cycles 2-6; chlorambucil was given orally at 0.5 mg/kg on days 1 and 15 of cycles 1-6.
RESULTS
Patient 1 at cycle 6 was able to stand, gait was possible with monolateral support, hypoesthesia and strength improved. M-protein and IgM level decreased. In patient 2, already after three cycles, the monoclonal component disappeared and there was dramatic improvement of symptoms and gait normalization. At the end of therapy anti-MAG antibody titer decreased to 5462 BTU. Neurophysiology also improved.
CONCLUSIONS
In our patients, obinutuzumab was effective as a first-line treatment of anti-MAG antibody polyneuropathy. CLL might have had a role in the response to therapy, but the associations might be considered in future trials.

Identifiants

pubmed: 30315672
doi: 10.1111/ene.13838
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Autoantibodies 0
Immunoglobulin M 0
Myelin-Associated Glycoprotein 0
Chlorambucil 18D0SL7309
obinutuzumab O43472U9X8

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

371-375

Informations de copyright

© 2018 EAN.

Auteurs

C Briani (C)

Neurology Unit, Department of Neuroscience, University of Padova, Padova, Italy.

A Visentin (A)

Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padova, Italy.

A Salvalaggio (A)

Neurology Unit, Department of Neuroscience, University of Padova, Padova, Italy.

M Cacciavillani (M)

CEMES, Data Medica Group, Padova, Italy.

L Trentin (L)

Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padova, Italy.

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Classifications MeSH