Resveratrol and simvastatin decrease IgM secretion in Waldenström macroglobulinemia: One-year follow-up.

Abstract

e18556 Background: Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder characterized by lympho plasmacytic bone marrow infiltration along with an immunoglobulin M (IgM) monoclonal gammopathy.Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. Published data show that resveratrol and simvastatin have significant antitumor activity in WM cells line. Data is still lacking on the use of these two drugs in vivo. Methods: 6 patients (3 males and 3 females), median age 41.5 yr (range, 42–73) and asymptomatic WM (IgM-MGUS or smouldering WM(SWM), were treated with resveratrol 40 mg/die and simvastatin 20 mg/die for at least 180 days. Immunoglobulin(Ig)-M monoclonal gammopathy of undetermined significance (IgM-MGUS) was defined as a serum IgM monoclonal protein < 3 g/dL,bone marrow lymphoplasmacytic infiltration < 10%, and no evidence of constitutional symptoms, anemia, hyperviscosity, lymphadenopathy, or hepatosplenomegaly related to the lymphoplasmacytic process. Smoldering Waldenström macroglobulinemia was defined as serum IgM monoclonal protein level ≥3 g/dL and/or bone marrow lymphoplasmacytic infiltration ≥10% and no evidence of end-organ damages.At enrollment patients characteristic were: Hb level median, 12.3 g/dL, serum beta(2)-microglobulin level median 2.4 mg/L, and IgM peaks median, 2.2 g/dL.5 patients were classified as IgM-MGUS and only one patient as SWM because of bone marrow lymphoplasmacytic infiltration > 10%. All patients took regularly the drugs and there have been no adverse events.CK and LDH serum levels were kept in the normal range. Results: In all IgM-MGUS patients a reduction between 30 and 50% of the IgM peak was observed after 6 months of therapy and is still maintained at 14 months of follow-up.In SWM patient the reduction was about 25% and is maintained over time. Conclusions: Our data demonstrate clearly that the association between resveratrol with simvastatin decreases IgM secretion both in IgM-MGUS and in smouldering patients not having any adverse effects. No significant financial relationships to disclose.