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

Abstract

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 >70000 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 >70000 BTU. Both patients were treated with obinutuzumab intravenously at 100mg on day +1, 900mg +2, then at 1000mg on days 8 and 15 of cycle 1 and day 1 of cycles 2-6; chlorambucil was given orally at 0.5mg/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.