title: Efficacy of lenalidomide in myelodysplastic syndromes.
abstract: BACKGROUND
  Ineffective erythropoiesis is the hallmark of myelodysplastic syndromes. Management of the anemia caused by ineffective erythropoiesis is difficult. In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the safety and hematologic activity of lenalidomide, a novel analogue of thalidomide.
  
  
  METHODS
  Forty-three patients with transfusion-dependent or symptomatic anemia received lenalidomide at doses of 25 or 10 mg per day or of 10 mg per day for 21 days of every 28-day cycle. All patients either had had no response to recombinant erythropoietin or had a high endogenous erythropoietin level with a low probability of benefit from such therapy. The response to treatment was assessed after 16 weeks.
  
  
  RESULTS
  Neutropenia and thrombocytopenia, the most common adverse events, with respective frequencies of 65 percent and 74 percent, necessitated the interruption of treatment or a dose reduction in 25 patients (58 percent). Other adverse events were mild and infrequent. Twenty-four patients had a response (56 percent): 20 had sustained independence from transfusion, 1 had an increase in the hemoglobin level of more than 2 g per deciliter, and 3 had more than a 50 percent reduction in the need for transfusions. The response rate was highest among patients with a clonal interstitial deletion involving chromosome 5q31.1 (83 percent, as compared with 57 percent among those with a normal karyotype and 12 percent among those with other karyotypic abnormalities; P=0.007) and patients with lower prognostic risk. Of 20 patients with karyotypic abnormalities, 11 had at least a 50 percent reduction in abnormal cells in metaphase, including 10 (50 percent) with a complete cytogenetic remission. After a median follow-up of 81 weeks, the median duration of transfusion independence had not been reached and the median hemoglobin level was 13.2 g per deciliter (range, 11.5 to 15.8).
  
  
  CONCLUSIONS
  Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy.
authors.affiliation: Department of Interdisciplinary Oncology, University of South Florida and the H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612-9497, USA. listaf@moffitt.usf.edu
authors.forename: Alan
authors.initials: A
authors.lastname: List
authors.forename: Sandy
authors.initials: S
authors.lastname: Kurtin
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Roe
authors.forename: Andrew
authors.initials: A
authors.lastname: Buresh
authors.forename: Daruka
authors.initials: D
authors.lastname: Mahadevan
authors.forename: Deborah
authors.initials: D
authors.lastname: Fuchs
authors.forename: Lisa
authors.initials: L
authors.lastname: Rimsza
authors.forename: Ruth
authors.initials: R
authors.lastname: Heaton
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000188:drug therapy* / Q000209:etiology; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide