Characteristics of Patients with Anti-MAG Associated Neuropathy who Respond to Rituximab (5242)

Objective: To assess the long-term response of patients treated with rituximab and describe the characteristics of those with favorable outcomes. Background: Anti-myelin associated glycoprotein (MAG) neuropathy is a debilitating paraproteinemic demyelinating neuropathy. Efficacy of immunotherapy has been inconsistent across multiple studies; however, rituximab—a B-cell depleting agent—has been shown to be beneficial in a subset of patients. Design/Methods: Case-series of 7 patients with anti-MAG neuropathy on rituximab. Records reviewed for demographic, serological, and electrodiagnostic features. Outcomes to assess efficacy include modified Rankin scale (mRS) and inflammatory neuropathy cause and treatment (INCAT) scale. Results: 86% of patients were white men. At diagnosis, the mean age was 57 years and the average anti-MAG titer was 1:40,000 in responders and 1:513,600 in non-responders (p=0.04). Disease-duration prior to therapy initiation was 4±3 years in responders, compared to 11±7 years in non-responders (p=0.05). Titers decreased by 7.5±4.7 folds after treatment. At 12 months post-treatment, 4/7 patients reported symptomatic improvement of paresthesia, allodynia, tremor and gait. Neurologic examination demonstrated recovery of distal strength, vibration and proprioception with resolution of Romberg’s sign, and re-emergence of reflexes in the lower extremities. INCAT (mRS) score improved by 1.8±1.0, (p=0.01) (1.3±0.5, p=0.004) points from a baseline of 3.0±1.6 (2.3±0.5). Terminal latency index (TLI) of the median nerve was 0.30±0.05. The remaining patients did not have further deterioration in their symptoms, exam or scores. One patient had lambda light-chains, unlike the others with kappa light-chains, and did not improve. Another elderly patient with TLI of 0.18 did not respond either despite a 9-fold reduction in anti-MAG titer. Conclusions: Features of rituximab responders include shorter disease-duration, lower anti-MAG titers and TLI>0.25. Non-responders did not deteriorate further and remained stable. This retrospective case-series supports rituximab as a viable option in a subset of patients for management of anti-MAG neuropathy, with improvements in symptoms, neurological exam and functional neuropathy scales. Disclosure: Dr. Chaar has nothing to disclose. Dr. Kakara has nothing to disclose. Dr. Sriwastava has nothing to disclose. Dr. Moshirzadeh has nothing to disclose. Dr. Halon has nothing to disclose. Dr. Lisak has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Argenix, Novartis, Syntimmune, Teva Pharmaceuticals (non-branded talks), Alpha Sites, Clearview Consulting, Destum, GLG consulting, Haven Consulting, Informa Consulting, Insights Pharma Consulting, Slingshot Consulting. Dr. Lisak has received research support from Catalyst, Chungai, Genentec/Roche, Mallinckdrot, Medimmune, Novartis, Ra Pharmaceuticals, Teva Phamaceuticals.