A Prospective, Randomized, Chemoprevention Trial of Celecoxib for High Risk Monoclonal Gammopathy of Undetermined Significance and Asymptomatic Multiple Myeloma

Abstract 5045

Observation remains the standard approach to patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic multiple myeloma (AMM) who lack end-organ impairment characteristic of symptomatic MM. Institution of early MM therapy has not been shown to improve survival or alter the natural progression of the disease. Cyclooxygenase-2 (COX2) inhibitors inhibit proliferation and induce apoptosis in drug resistant MM cell lines. 23 asymptomatic adult patients with a serum monoclonal protein >1g/dL, from Cleveland Clinic, Mayo Clinic, or University of Arkansas Medical Center between August 2005 and April 2008 were randomized to either celecoxib or placebo in a double-blind, 1:1 fashion. The primary end point was change in the monoclonal protein concentration after 6 months. Correlative biomarkers, including IL6 and IL-6R, CD4/CD8+ T-cell ratios, and beta-2 microglobulin, were examined before and after treatment. Celecoxib had no significant effect on the median monoclonal protein concentration, which went from a median of 1. 44 to 1. 65 g/dL with placebo and 2. 42 to 2. 24 g/dL with Celecoxib (p=0. 36), or on any of the analyzed correlative markers (all p-values >0. 34). One patient's monoclonal protein concentration increased on placebo, but he did not require treatment for symptomatic MM. There were no adverse events of Grade 2 or higher. Celecoxib was well tolerated in contrast to previous reports when given in higher doses and in combination with thalidomide. Although accrual was limited we conclude that celecoxib has no clinical or immunologic effect on high risk asymptomatic plasma cell disorders. This study does not support using celecoxib for preventing progression to symptomatic MM. Future studies on progression of MGUS to symptomatic MM would require more patients and a longer follow-up period.