title: Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma.
abstract: The treatment of patients with multiple myeloma usually includes many drugs including thalidomide, lenalidomide and bortezomib. Lovastatin and other inhibitors of HMG-CoA reductase demonstrated to exhibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines. We treated 91 patients with relapsed or refractory multiple myeloma with thalidomide, dexamethasone and lovastatin (TDL group, 49 patients) or thalidomide and dexamethasone (TD group, 42 patients). A clinical response defined of at least 50% reduction of monoclonal band has been observed in 32% of TD patients and 44% of TDL patients. Prolongation of overall survival and progression-free survival in the TDL group as compared with the TD group has been documented. The TDL regimen was safe and well tolerated. The incidence of side effects was comparable in both groups. Plasma cells have been cultured in vitro with thalidomide and lovastatin to assess the impact of both drugs on the apoptosis rate of plasma cells. In vitro experiments revealed that the combination of thalidomide and lovastatin induced higher apoptosis rate than apoptosis induced by each drug alone. Our results suggest that the addition of lovastatin to the TD regimen may improve the response rate in patients with relapsed or refractory myeloma.
authors.affiliation: Department of Haematology and Bone Marrow Transplantation, Medical University of Lublin, Staszica 11, Lublin, Poland. markhus@o2.pl
authors.forename: Marek
authors.initials: M
authors.lastname: Hus
authors.forename: Norbert
authors.initials: N
authors.lastname: Grzasko
authors.forename: Marta
authors.initials: M
authors.lastname: Szostek
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pluta
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Helbig
authors.forename: Dariusz
authors.initials: D
authors.lastname: Woszczyk
authors.forename: Maria
authors.initials: M
authors.lastname: Adamczyk-Cioch
authors.forename: Dariusz
authors.initials: D
authors.lastname: Jawniak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Legiec
authors.forename: Marta
authors.initials: M
authors.lastname: Morawska
authors.forename: Justyna
authors.initials: J
authors.lastname: Kozinska
authors.forename: Piotr
authors.initials: P
authors.lastname: Waciński
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008148:Lovastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D016879:Salvage Therapy / Q000009:adverse effects; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014182:Transplantation, Autologous
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D013792:Thalidomide; D003907:Dexamethasone; D008148:Lovastatin