title: The combination of intermediate doses of thalidomide with dexamethasone is an effective treatment for patients with refractory/relapsed multiple myeloma and normalizes abnormal bone remodeling, through the reduction of sRANKL/osteoprotegerin ratio.
abstract: The aim of this study was the evaluation of the effect of intermediate doses of thalidomide with dexamethasone (Thal/Dex) on disease course and bone disease in patients with refractory/relapsed myeloma who were under zoledronic acid therapy. We studied 35 patients, who received thalidomide at a dose of 200 mg/daily. We measured, pre-, 3 and 6 months post-treatment soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), osteoprotegerin (OPG), osteopontin (OPN), markers of bone resorption and formation. Before treatment, patients had increased levels of sRANKL/OPG ratio, bone resorption markers and OPN, while they had suppressed bone formation. The pretreatment sRANKL/OPG ratio correlated with the extent of bone disease. Thal/Dex administration resulted in a significant reduction of sRANKL/OPG ratio, and bone resorption. Bone formation, OPG and OPN did not show any alteration. Changes of sRANKL/OPG ratio correlated with changes of bone resorption markers. Thal/Dex was given for a median time of 10 months and the median follow-up period was 22 months. The response rate was 65.7%. The median survival was 19.5 months. beta2-microglobulin, type of response and International Staging System predicted for survival. These results suggest that the combination of intermediate dose of Thal/Dex is effective in patients with refractory/relapsed myeloma and improves abnormal bone remodeling through the reduction of sRANKL/OPG ratio.
authors.affiliation: Department of Hematology, 251 General Airforce Hospital, Athens, Greece. e.terpos@imperial.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Terpos
authors.forename: D
authors.initials: D
authors.lastname: Mihou
authors.forename: R
authors.initials: R
authors.lastname: Szydlo
authors.forename: K
authors.initials: K
authors.lastname: Tsimirika
authors.forename: C
authors.initials: C
authors.lastname: Karkantaris
authors.forename: M
authors.initials: M
authors.lastname: Politou
authors.forename: E
authors.initials: E
authors.lastname: Voskaridou
authors.forename: A
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: K
authors.initials: K
authors.lastname: Zervas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D016723:Bone Remodeling / Q000187:drug effects* / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D053495:Osteopontin; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D012795:Sialoglycoproteins / Q000032:analysis; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D008024:Ligands; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506030:TNFRSF11B protein, human; D053495:Osteopontin; D013792:Thalidomide; D003907:Dexamethasone