title: Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies.
abstract: We prospectively studied the impact of several cytogenetic abnormalities (CAs) in patients with relapsed/refractory myeloma who received lenalidomide and dexamethasone (RD) with or without the addition of bortezomib (V). On the basis of the presence of previous neuropathy, 50 patients were treated with RD and 49, without preexisting neuropathy, with VRD. The overall response rate was 63%, similar for RD and VRD. Poor risk cytogenetics were associated with lower response rates in RD (P=0.01), but not in VRD (P=0.219). The median progression-free survival (PFS) was similar for RD (9 months) and VRD (7 months). The median overall survival (OS) for all patients was 16 months, with no differences between RD or VRD regimens. Poor risk cytogenetics, especially del17p, resistance to previous thalidomide, elevated lactate dehydrogenase (LDH) and presence of extramedullary disease were associated with inferior response to therapy and shorter PFS and OS. The impact of other CAs on OS was more pronounced in RD. In conclusion, the presence of CAs is an important adverse prognostic factor for patients with relapsed/refractory myeloma, but resistance to previous thalidomide, elevated LDH and presence of extramedullary disease remain of major prognostic importance. The outcome of patients with del17p remains extremely poor even with VRD combination.
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. mdimop@med.uoa.gr
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: E
authors.initials: E
authors.lastname: Kastritis
authors.forename: D
authors.initials: D
authors.lastname: Christoulas
authors.forename: M
authors.initials: M
authors.lastname: Migkou
authors.forename: M
authors.initials: M
authors.lastname: Gavriatopoulou
authors.forename: M
authors.initials: M
authors.lastname: Gkotzamanidou
authors.forename: M
authors.initials: M
authors.lastname: Iakovaki
authors.forename: C
authors.initials: C
authors.lastname: Matsouka
authors.forename: D
authors.initials: D
authors.lastname: Mparmparoussi
authors.forename: M
authors.initials: M
authors.lastname: Roussou
authors.forename: E
authors.initials: E
authors.lastname: Efstathiou
authors.forename: E
authors.initials: E
authors.lastname: Terpos
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002869:Chromosome Aberrations / Q000139:chemically induced*; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D000077269:Lenalidomide; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000188:drug therapy; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide