title: The combination of lenalidomide and dexamethasone reduces bone resorption in responding patients with relapsed/refractory multiple myeloma but has no effect on bone formation: final results on 205 patients of the Greek myeloma study group.
abstract: The combination of lenalidomide plus dexamethasone (RD) is very effective for patients with relapsed/ refractory myeloma. However, the effect of RD on bone metabolism has not been previously evaluated in these patients. To address this issue, we initially performed a retrospective study in 106 consecutive patients with relapsed or refractory myeloma who received RD. We measured the following bone indices on Cycle 1/Day 1 and then on Cycles 3 and 6/Day 28: dickkopf-1 (Dkk-1), sRANKL, osteoprotegerin (OPG), bone resorption markers (C-telopeptide of collagen type-I, CTX and TRACP-5b) and bone formation markers (bone-specific alkaline phosphatase-bALP and osteocalcin). RD produced a reduction of CTX only in responders, with no effect on bone formation. To validate these results, we then evaluated prospectively 99 patients who received either RD (n550) or VRD (bortezomib + RD, n549). RD reduced CTX, mainly in responders but showed no effect on bone formation, confirming the result of the retrospective study. However, the addition of bortezomib to RD (VRD arm) reduced Dkk-1, sRANKL/OPG, and CTX, while it increased bALP and OC after six cycles of therapy. These changes were irrespective of treatment response, which was similar between treatment arms. No skeletal-related events were observed in the VRD arm while two, nonresponding patients treated with RD developed a vertebral fracture. We conclude that RD reduces bone resorption only in responding patients with relapsed/refractory myeloma but has no effect on bone formation. Combination with bortezomib, which enhances bone formation, seems to be preferred for the management of myeloma patients with osteolytic disease.
authors: Evangelos
authors: E
authors: Terpos
authors: Dimitrios
authors: D
authors: Christoulas
authors: Efstathios
authors: E
authors: Kastritis
authors: Eirini
authors: E
authors: Katodritou
authors: Athanasios
authors: A
authors: Papatheodorou
authors: Anastasia
authors: A
authors: Pouli
authors: Marie-Christine
authors: MC
authors: Kyrtsonis
authors: Eurydiki
authors: E
authors: Michalis
authors: Xenophon
authors: X
authors: Papanikolaou
authors: Maria
authors: M
authors: Gkotzamanidou
authors: Efstathios
authors: E
authors: Koulieris
authors: Maria
authors: M
authors: Gavriatopoulou
authors: Konstantinos
authors: K
authors: Zervas
authors: Meletios A
authors: MA
authors: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006115:Greece; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010012:Osteogenesis / Q000187:drug effects*; D012008:Recurrence; D012189:Retrospective Studies; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide