title: Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS.
abstract: Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥ 8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥ 8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: List
authors.affiliation: Departments of Oncology and Pathology, James P. Wilmot Cancer Center, Rochester, NY, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Bennett
authors.affiliation: Leukemia Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Sekeres
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: B
authors.initials: B
authors.lastname: Skikne
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: T
authors.initials: T
authors.lastname: Fu
authors.affiliation: Rush University Medical Center, Chicago, IL, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Shammo
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, New York, NY, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Nimer
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Knight
authors.affiliation: Clinic for Oncology, Hematology and Palliative Medicine, Marien Hospital, Düsseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Giagounidis
mesh_terms: D000368:Aged; D002872:Chromosome Deletion; D018450:Disease Progression; D017707:Erythrocyte Transfusion; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D016019:Survival Analysis; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide