Immunotherapy-based regimen in anti-MAG neuropathy: results in 45 patientsThe prevalence of neuropathy in patients with immunoglobulin M (IgM) monoclonal gammopathies ranges from 5% to 31%.1 The most frequent neuropathy is associated with monoclonal IgM reacting with myelinassociated glycoprotein (MAG) and is usually a chronic demyelinating disorder that typically presents with progressive ataxia and painful paresthesias.2 The clinical features of neuropathies associated with Waldenstrom's macroglobulinemia (WM) and IgM-monoclonal gammopathy of unknown significance are similar.3 Treatment is only warranted in case of significant disability and should not be based on the IgM level or bone marrow infiltration. 4 Intravenous immunoglobulin (IVIg), interferon alpha, plasma exchange and immunosuppressive therapy have all been used, but there is no consensus treatment. 5More effective therapy is therefore needed as 30-40% of patients are disabled by severe, progressive neuropathies that undermine their quality of life.6 Several open-label trials of rituximab, a chimeric mouse-human monoclonal antibody directed against the B-cell surface protein CD20, have given encouraging results.7,8 Moreover, even though no randomized controlled trials have provided evidence of improvement in primary outcome measures, several secondary outcomes were improved.9,10 In WM and other indolent B-cell lymphomas, rituximab combined with nucleoside analogs or with nucleoside analogs plus alkylating agents, yields better responses than rituximab monotherapy.4 Based on these results, we wondered whether patients with anti-MAG neuropathy might benefit more from rituximab plus chemotherapy (immunochemotherapy) than from rituximab alone (immunotherapy).In this retrospective study, we therefore compared our experience with immunochemotherapy and rituximab monotherapy in 45 patients treated for anti-MAG neuropathy at Salpêtrière Hospital, Paris, France, from 1996 to 2011. Apart from symptomatic neuropathy, none of these patients met the criteria for treatment initiation defined by the second WM international workshop. The treatment choice was based on the aggressiveness of the neuropathy and its rate of progression. To evaluate the treatment response we used the Rankin Score (RS) that measures the degree of disability or dependence for daily activities. The scale ranges from 0 to 5, as described in Table 1. Improvement was defined as a 1 point or more decrease in the RS score, stabilization as an unchanged RS, and progression as a 1 point or more increase. -20). There was no difference in the median time to response between patients receiving first-line treatment (6 months, range 2-17) and previously treated patients (6.5 months, range 3-20). The base-line Rankin score was similar in the 3 groups. Because of the small size of the groups, however, it was difficult to assess the benefit of each combination individually. One patient relapsed after a median of 24 months. Three patients developed cytopenia requiring blood and platelet transfusion and o...
3951 Background: Polyneuropathy is the most frequent neurological complication in Waldenstrom macroglobulinemia (WM). Most patients have an insidiously progressive distal symmetric sensorimotor and ataxic neuropathy due to a monoclonal immunoglobulin M anti-myelin-associated glycoprotein (MAG). There is still no treatment reference today. Recent studies underline the interest of Rituximab (RTX) but its efficacy is not yet proven. In order to identify the interest of immunotherapy, we performed a retrospective study in 61 patients with anti-MAG over a period of 12 years. Methods: All patients underwent neurological, biological (anti-MAG antibodies, IgM serum) and electrophysiological examination before and after each treatment. Clinically, patients were considered to be improved if they had a decrease of at least two points on the INCAT sensory sum score and/or a decrease of 20 mm on the visual analogue scale and/or motor strength improvement by at least two MRC points in the ankle dorsiflexor. Biologically, response anti-MAG antibodies and IgM serum were considered to be improved if their level was diminished by half. Electrophysiological studies were performed using standard procedures. Results: A total of 61 patients were analyzed. The median age at onset was 64 years (range 33–84), median serum IgM concentration 4.6 g/L (0-17), median anti-MAG antibodies 49900 BTU (23000>70000), RANKIN score 1 (35 patients), 2(20 patients), 3(6 patients). Twenty-five patients had WM with lymphoplasmacytic cells bone marrow infiltration. None of the patients had criteria for therapy initiation according to the 2th international workshop except symptomatic or evolving neuropathy. In first line, 45 patients were treated with Chlorambucil (CBL) (8 improved, 28 were stabilised, 9 worsened), 16 patients were treated with RTX alone (9) or in combination (7) (11 improved, 2 were stabilised, 3 worsened). RTX gave a significant higher response rate compared with CBL (p=2×10-4). With a median follow up of 96 months, 15 patients treated with CBL relapsed. Only one patient treated with RTX relapsed but the median follow up was not reached (60 months follow up). In the CBL group, 15 patients were treated at relapse with RTX and 11 improved, 3 were stabilised, 1 worsened. The average time follow up of the 2nd response was 48 months. Twelve patients in failure were treated with RTX: 8 improved, 1 was stabilised, 3 failed with an average follow up of 48 months. There was no significant difference between anti-MAG antibodies level before and after treatment (p=0.64) in patients in response but a low IgM level was associated with response to treatment (p<0.029). Conclusion: In first line, RTX alone or in combination is associated with a higher response rate than CBL. For patients who relapsed after CHL, patients favourably responded to RTX with an average time follow up of 48 months. IgM level is a prognosis factor (p<0.029) for clinical response to treatment. To better define the efficacy of RTX in this setting, results of a french randomized study comparing RTX to placebo are pending. Disclosures: Choquet: Roche: Consultancy. Leblond:ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GENZYME: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees.
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