Fludarabine may overcome resistance to rituximab in IgM-related neuropathy.

Rituximab, a monoclonal antibody directed against CD20, became widely used for the treatment of immunoglobulin M (IgM)-related neuropathy. However, response rate by rituximab monotherapy is no more than 30%. Previous studies revealed that fludarabine acts synergistically with rituximab in vitro and that fludarabine also ameliorates IgM-related neuropathy in a subset of patients. Here we present two cases of IgM-related neuropathy in the background of Waldenström macroglobulinaemia, including one with rituximab resistance. They showed marginal to high titres of both anti-myelin associated glycoprotein and anti-sulphate-3-glucuronyl paragloboside antibodies, and their symptoms were featured by prominent motor deterioration. The combination therapy with rituximab and fludarabine stabilised or improved neuropathic symptoms with tolerable adverse events. Fludarabine may have a potential to overcome rituximab resistance. In conclusion, combination therapy with rituximab and fludarabine should be considered for IgM-related neuropathy, especially when efficacy of rituximab monotherapy is insufficient.