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RE: Obinutuzumab, a new anti-CD20 antibody, is active and effective in anti-MAG antibody polyneuropathy.

  • Chiara Briani, Neurologist, Department of Neurosciences, University of Padova, Italy
  • Andrea Visentin, Hematologist, Hematology Unit, Department of Medicine, University of Padova, Italy
  • Alessandro Salvalaggio, Neurology resident, Department of Neurosciences, University of Padova, Italy
  • Mario Cacciavillani, Neurophysiologist, CEMES, Data-Medica Group, Padova
  • Livio Trentin, Hematologist, Hematology Unit, Department of Medicine, University of Padova, Italy
Submitted April 16, 2018

We read with interest the paper on obinutuzumab in anti-MAG neuropathy [1], and would like to report our experience with two patients successfully treated with obinutuzumab.
The first patient is a 82-year-old man with severe demyelinating sensory-motor neuropathy. He was wheelchair-bound, incapable of standing, with loss of sensation up to the knees. He had chronic lymphocytic leukemia (CLL) with IgM lambda monoclonal gammopathy and anti-MAG antibodies >70,000BTU. He was treated with obinutuzumab at the same reported dosage [1] and chlorambucil (0.5mg/kg at day 1 and 15 of cycles 1-6) [2]. After 6 cycles of treatment the patient was able to stand and walk with monolateral support, and his hypoesthesia and strength improved. M-protein and IgM levels decreased.
The second patient is a 84-year-old women with demyelinating neuropathy, paresthesia and gait instability. She had CLL and IgM kappa paraprotein with anti-MAG antibodies >70,000 BTU. Chlorambucil and obinutuzumab were administered. After 3 cycles the monoclonal component disappeared and the patient reported dramatic improvement of symptoms and gait normalization.
In our patients, obinutuzumab was effective as first-line treatment of anti-MAG antibody polyneuropathy.
Control of the underlying disease (CLL) might have had an important role in the response to therapy,[3] but chlorambucil+obinutuzumab might be considered in future trials in anti-MAG antibody polyneuropathy,[2,4] regardless of the associated hematological condition.

References
1. Rakocevic G, Martinez-Outschoorn U, Dalakas MC. Obinutuzumab, a potent anti-B-cell agent, for rituximab-unresponsive IgM anti-MAG neuropathy. Neurol Neuroimmunol Neuroinflamm. 2018;5:e460.
2. Goede V, Fischer K, Engelke A et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia. 2015;29:1602-1604.
3. Briani C, Visentin A, Salvalaggio A et al. Peripheral neuropathies in chronic lymphocytic leukemia: a single center experience on 816 patients. Haematologica. 2017;102:e140-e143.
4. Nobile-Orazio E, Bianco M, Nozza A. Advances in the Treatment of Paraproteinemic Neuropathy. Curr Treat Options Neurol. 2017;19:43.

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