title: Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure.
abstract: This analysis assessed the efficacy and safety of lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma (MM) previously treated with thalidomide. Of 704 patients, 39% were thalidomide exposed. Thalidomide-exposed patients had more prior lines of therapy and longer duration of myeloma than thalidomide-naive patients. Lenalidomide + dexamethasone led to higher overall response rate (ORR), longer time to progression (TTP), and progression-free survival (PFS) versus placebo + dexamethasone despite prior thalidomide exposure. Among lenalidomide + dexamethasone-treated patients, ORR was higher in thalidomide-naive versus thalidomide-exposed patients (P = .04), with longer median TTP (P = .04) and PFS (P = .02). Likewise for dexamethasone alone-treated patients (P = .03 for ORR, P = .03 for TTP, P = .06 for PFS). Prior thalidomide did not affect survival in lenalidomide + dexamethasone-treated patients (36.1 vs 33.3 months, P > .05). Thalidomide-naive and thalidomide-exposed patients had similar toxicities. Lenalidomide + dexamethasone resulted in higher rates of venous thromboembolism, myelosuppression, and infections versus placebo + dexamethasone, independent of prior thalidomide exposure. Lenalido-mide + dexamethasone was superior to placebo + dexamethasone, independent of prior thalidomide exposure. Although prior thalidomide may have contributed to inferior TTP and PFS compared with thalidomide-naive patients, these parameters remained superior compared with placebo + dexamethasone; similar benefits compared with placebo + dexamethasone were not evident for thalidomide-exposed patients in terms of overall survival. Studies were registered at http://www.clinicaltrials.gov under NCT00056160 and NCT00424047.
authors.affiliation: Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX 77030, USA. miwang@mdanderson.org
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Cibeira
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Zhinuan
authors.initials: Z
authors.lastname: Yu
authors.forename: Marta
authors.initials: M
authors.lastname: Olesnyckyj
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: Robert D
authors.initials: RD
authors.lastname: Knight
authors.forename: Donna M
authors.initials: DM
authors.lastname: Weber
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D000077269:Lenalidomide; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide