Rituximab for Neuropathy with IgM Monoclonal Gammopathy
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports he has no financial relationships relevant to this field of study.
Synopsis: In preliminary, open-label trials, rituximab shows promise as a treatment for IgM-associated neuropathy.
Source: Niermeijer JMF, Eurelings M, Lokhorst HL, et al. Rituximab for polyneuropathy with IgM monoclonal gammopathy. J Neurol Neurosurg Psychiatry 2009;80; 1036-1039
Among 17 patients with progressive or disabling polyneuropathy and IgM monoclonal gammopathy, encompassing three women and 14 men, intravenous rituximab 375 mg/m2 was administered in an open-label trial once weekly for four weeks, with subsequent follow-up for a median of 12 months. Age of onset ranged from 44 years to 67 years (median 55 years), duration from two years to 14 years (median seven years), and all but one had demyelinating, rather than axonal, polyneuropathy. Previous treatments in five patients included intermittent combined cyclophosphamide and prednisone, with fludarabine added in two. Electrodiagnostic studies were performed prior to and nine months following treatment initiation. Improvement of the Overall Disability Sum Score (ODSS) by one or more points was the primary outcome measure. Secondary outcome measures included improvement of the Modified Rankin Scale (MRS) by one or more points, distal MRC (motor) or sensory sum score improvement by 5% or more, nerve conduction velocity improvement, drop in M protein concentration, or disappearance of CD20-positive B cells in bone marrow, and adverse events. Statistical analysis included the Wilcoxon matched pairs test, the Mann-Whitney U test, and the X2 test, with p <0.05 considered statistically significant.
Rituximab resulted in improved sensory sum score in 9/17 patients, improved MRS in 5/17 patients, improved MRC (motor) sum score in 4/17 patients, and improved ODSS in two patients. CD20-positive B cells were depleted in the bone marrow in all patients and median IgM concentration significantly decreased following treatment. Nerve conduction velocities improved by 10% or more in 4/17 patients in two or more nerves, and in 2/17 patients in a single nerve. No serious adverse events were recorded during the study period. Rituximab response rate in polyneuropathy with IgM monoclonal gammopathy is comparable to that seen with combined cyclophosphamide and prednisone or fludarabine, and warrants further investigation in controlled clinical trials.
Commentary
Rituximab, a chimeric monoclonal antibody against the CD20 protein on B-lymphocytes, is beneficial against a host of diseases, including autoimmune disorders (rheumatoid arthritis, idiopathic thrombocytopenic purpura, myasthenia gravis), lymphoma, and leukemia. Lambert-Eaton myasthenic syndrome (LEMS) may soon be added to the list. (See Pellkofer HL, Voltz R, Kuempfel T. Favorable response to rituximab in a patient with anti-VGCC-positive Lambert-Eaton myasthenic syndrome and cerebellar dysfunction. Muscle Nerve 2009;40;305-308).
In this case report, a 61-year-old-man was wheelchair bound after a five-year history of coincident non-paraneoplastic Lambert-Eaton myasthenic syndrome and subacute severe cerebellar degeneration. Rituximab administration resulted in symptomatic improvement following poor response to intravenous immunoglobulin infusion, steroids, azathioprine, and plasma exchange. Dysarthria and dysphagia abated and he was able to ambulate 200 m to 300 m without assistance. With worsening of symptoms and reappearance of B cells, improvement was recaptured with depletion of B cells following repeat rituximab infusions. Well-tolerated and safe, rituximab may be a therapeutic option for LEMS when other treatments fail.
In preliminary, open-label trials, rituximab shows promise as a treatment for IgM-associated neuropathy.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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