title: A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide.
abstract: BACKGROUND
  Lenalidomide treatment in myelodysplastic syndrome (MDS) may lead to thrombocytopenia and dose reductions/delays. This study evaluated the safety and tolerability of the thrombopoietin mimetic romiplostim and its effects on the incidence of clinically significant thrombocytopenic events (CSTEs) in lower risk MDS patients receiving lenalidomide.
  
  
  METHODS
  Patients were assigned to weekly placebo (n = 12) or romiplostim 500 μg (n = 14) or 750 μg (n = 13) for four 28-day lenalidomide cycles.
  
  
  RESULTS
  The treatment groups were generally similar with respect to baseline disease characteristics. Del(5q) abnormalities were noted in 1 (8%) patient in the placebo group, 3 (21%) in the romiplostim 500 μg group, and two (15%) in the 750 μg group. CSTEs were noted in 8 (67%) patients in the placebo group, 4 (29%) in the romiplostim 500 μg group, and 8 (62%) in the romiplostim 750 μg group. Throughout the study, median platelet counts trended lower in placebo-treated than in romiplostim-treated patients. Thrombocytopenia-related adjustments in lenalidomide occurred in 6 (50%) patients in the placebo group, 5 (36%) in the romiplostim 500 μg group, and 2 (15%) in the 750 μg group. Although the percentages of patients who received platelet transfusions were similar across treatment groups, there was a trend toward lower numbers of transfusions in both romiplostim groups during each treatment cycle. There were two serious treatment-related adverse events during the treatment period (cerebrovascular accident, placebo; worsening thrombocytopenia, romiplostim 500 μg). Two patients (romiplostim 500 and 750 μg, respectively) had an increase in bone marrow blasts to >20% during treatment, but had no post-treatment biopsy to confirm or exclude the diagnosis of progression to AML.
  
  
  CONCLUSIONS
  These data suggest that romiplostim administered to MDS patients during lenalidomide treatment may decrease the frequency of dose reductions/delays due to thrombocytopenia. Additional study is needed to confirm the results of this preliminary trial.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00418665.
authors.affiliation: Leukemia Service, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. eunice.wang@roswellpark.org
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Sunil
authors.initials: S
authors.lastname: Gandhi
authors.forename: Delong
authors.initials: D
authors.lastname: Liu
authors.forename: Carmen
authors.initials: C
authors.lastname: Matei
authors.forename: Bart
authors.initials: B
authors.lastname: Scott
authors.forename: Kuolung
authors.initials: K
authors.lastname: Hu
authors.forename: Allen S
authors.initials: AS
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D010919:Placebos; D011961:Receptors, Fc / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013926:Thrombopoietin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D010919:Placebos; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013792:Thalidomide; D013926:Thrombopoietin; D000077269:Lenalidomide; C488777:romiplostim