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Within the spectrum of chronic immune-mediated neuropathies, demyelinating neuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy and antibodies against myelin-associated glycoprotein (MAG) is a distinct entity that typically presents with progressive sensory ataxia and painful paresthesias. Several studies recently suggested that these patients can respond to rituxumab.

The Europena Fenderation of Neurological Societies issued a very mild recommendation for this treatment in 2010. It said: ” In the absence of adequate evidence, the panel agreed on good practice points: (1) patients with PDN should be investigated for a malignant plasma cell dyscrasia; (2) a monoclonal gammopathy of undetermined significance is more likely to be causing the neuropathy if it is immunoglobulin (Ig)M, anti-neural antibodies are present, and the clinical phenotype is chronic distal sensory neuropathy; (3) patients with IgM PDN usually have predominantly distal sensory impairment, prolonged distal motor latencies, and often anti-myelin-associated glycoprotein antibodies; (4) IgM PDN may respond to immunomodulatory therapies. Their potential benefit should be balanced against possible side effects and the usually slow disease progression; (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy; and (6) Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes syndrome is a multi-system malignant PDN.”

In the setting of monclonal gammopathy, a recent review article by Rison and Beydoun pointed out that several monoclonal antibody-producing conditions are associated with peripheral neuropathy, and in these circumstances, the constellation of neurological symptoms are often referred to as paraproteinemic neuropathy (PPN). As neuropathy is relatively common with M-protein and vice-vers, PPN may therefore be defined further as a heterogeneous group of neuropathies, which share the common feature of a homogeneous immunoglobulin in the serum. Therapies depend on the particular PPN subtype and the pathophysiology involved, and range from intravenous immunoglobulin (IVIG), plasma exchange, and corticosteroids to rituximab and various chemotherapies. There were two randomized studies of Rituxan which were not clearly positive, but suggested some improvement is some patients, and there are patients whose neuropathy worsens on this drug.

Richard A. Rison and Said R. Beydoun, Paraproteinemic neuropathy: a practical review. BMC NeurologyBMC series – open, inclusive and trusted201616:13

Jean-Marc Léger et al,Placebo-controlled trial of rituximab in IgM anti-myelin–associated glycoprotein neuropathy. Neurology. 2013 Jun 11; 80(24): 2217–2225.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision Joint Task Force of the EFNS and the PNS
© 2010 Peripheral Nerve Society, Journal of the Peripheral Nervous System. Volume 15, Issue 3, pages 185–195, September 2010

Marie-Anne Hospital et al, Immunotherapy-based regimen in anti-MAG neuropathy: results in 45 patients. Haematologica. 2013 Dec; 98(12): e155–e157.