Rituximab in Anti-Mag Associated Neuropathy : A Monocentric Experience.

Anti-MAG associated neuropathy is a rare disorder characterized by a sensory-motor polyneuropathy in the context of monoclonal IgM, which activity is directed against myelin-associated glycoprotein on the surface of myelin sheaths. Treatments are usually ineffective. Most common therapy is based on alkylating agents such as Chlorambucil, which however only rarely improve neurological tests nor induce disappearance of monoclonal component. More recently, the benefit of monoclonal anti-CD20 antibody Rituximab was reported in case reports. Thus, we have performed since 2002 a prospective pilot study to assess the benefit of Rituximab in anti-MAG associated neuropathy. We report here the first four successive patients treated.

Patients and Methods : inclusion criteria were as follow : peripheral sensory-motor polyneuropathy with clinical and electrophysiological symptoms compatible with anti-MAG associated neuropathy; serum monoclonal IgM; serum anti-MAG reactivity; absence of other cause of peripheral neuropathy such as amyloidosis; absence of underlying condition contra-indicating Rituximab therapy. Patients received 4 courses of Rituximab (375 mg/m²) with a 7 days interval between two infusions. Usual premedication with corticosteroids and paracetamol were administered. Evaluation of clinical, biological and immunochemical efficiency was performed every three months.

Results : characteristics of the first four patients treated are as follow : 3 males and 1 female; median age : 65 years (57 – 87); median time between onset of symptoms and Rituximab therapy : 4 years (3 – 6). Previous treatments were Chlorambucil (3/4), corticosteroids (2/4), intravenous Ig (1/4), anthracyclin-containing regimen (1/4), plasmapheresis (1/4). All were ineffective. Rituximab was well tolerated by all patients. Median follow-up after treatment is 2 years (1 – 3). None of the patients exhibit improvement of clinical neurological symptoms. Electrophysiological evaluation show only a mild improvement in 1 patient. Moreover, no decrease in monoclonal component nor disappearance of anti-MAG reactivity of serum were observed in any cases. Interestingly, one patient exhibited later neurological and biological improvement after high dose Melphalan followed by autologous stem cell transplantation.

Conclusion : Rituximab monotherapy does not seem to improve neurological outcome of patients with anti-MAG polyneuropathy as well as is unable to clear serum from monoclonal IgM. Therefore, new approaches are needed, for example with high dose chemotherapy with stem cell support in selected patients.