Thalidomide for the treatment of refractory multiple myeloma. decreased plasma concentration of angiogenic growth factors and clinical response

Recent studies showed that thalidomide has anti-myeloma effect, and anti-angiogenesis is suspected to be the mechanism. Therefore, thalidomide (100mg-400mg) was given to 12 cases with refractory multiple myeloma including 5 post-transplant relapse, and change of plasma concentrations of angiogenic growth factors by thalidomide treatment was examined. In 10 évaluable cases, three showed >70% reduction of M-protein, two showed >30% reduction and two showed stabilization of M-protein. In three out of 5 responders, anemia and suppression of normal immunoglobulin were alleviated. Treatment was well tolerated, and somnolence, constipation and peripheral neuropathy were frequent but reversible side effects. However, severe granulocytopenia (granulocytes <500/micro L) was also observed in three cases with pretreatment neutropenia (WBC <2000/micro L) due to advanced disease or repeated chemotherapy. Addition of thalidomide to the methylcellulose medium significantly reduced the number of bone marrow-derived CFU-GM colonies, suggesting direct negative regulation of thalidomide on granulopoiesis. In 10 évaluable cases, plasma concentrations of angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial cell growth factor (VEGF) were significantly elevated in 5 and 6 cases before thalidomide treatment, respectively. 4 out of 5 patients with high-pretreatment bFGF level and two out of 6 with high-pretreatment VEGF level showed clinical response along with decreased plasma concentration of growth factors. Our data suggested that down regulation of plasma growth factor level might contribute to anti-myeloma effect of thalidomide as one of the mechanisms. Table patients with high bFGF and VEGF level before treatment reduction of pretreatment posttreatment pretreatment posttreatment M protein bFGF bFGF VEGF VEGF casel -70.1% <7pg/ml <7pg/ml 208 pg/ml <36pg/ml case 2 -50.8 23.6 pg/ml <7pg/ml 111 pg/ml 89.7 pg/ml case 3 -31.5% 278 pg/ml 139 pg/ml 165 pg/ml 201 pg/ml case 4 stabilize 48.4 pg/ml 20.8 pg/ml ≤36pg/ml <36pg/ml case 5 stabilize 31.1 pg/ml <7pg/ml 96.1 pg/ml 89 pg/ml case 6 progress 35.7 pg/ml 10.2 pg/ml 114 pg/ml 38.5 pg/ml case 7 progress <7pg/ml <7pg/ml 182 pg/ml 164 pg/ml.