title: Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy.
abstract: We evaluated the efficacy and safety of romiplostim, a thrombopoietin mimetic, in patients with low- or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine therapy. Forty patients with low- or intermediate-risk MDS were stratified by baseline platelet counts (< 50 vs ≥ 50 × 10(9)/L) and randomized to romiplostim 500 μg or 750 μg or placebo subcutaneously once weekly during 4 cycles of azacitidine. The primary endpoint was the incidence of clinically significant thrombocytopenic events, defined by grade 3 or 4 thrombocytopenia starting on day 15 of the first cycle or platelet transfusion at any time during the 4-cycle treatment period. No formal hypothesis testing was planned. The incidence of clinically significant thrombocytopenic events in patients receiving romiplostim 500 μg, romiplostim 750 μg, or placebo was 62%, 71%, and 85%, respectively. The incidence of platelet transfusions was 46%, 36%, and 69%, respectively. These differences were not statistically significant with the small numbers in each group. Romiplostim 750 μg significantly raised median platelet counts during cycle 3 on day 1 (P = .0373) and at the nadir (P = .0035) compared with placebo. Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient (4%). This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy.
authors.affiliation: Leukemia Department, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. hkantarj@mdanderson.org
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Peter L
authors.initials: PL
authors.lastname: Greenberg
authors.forename: Ron L
authors.initials: RL
authors.lastname: Paquette
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: Janice L
authors.initials: JL
authors.lastname: Gabrilove
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Kuolung
authors.initials: K
authors.lastname: Hu
authors.forename: Janet L
authors.initials: JL
authors.lastname: Franklin
authors.forename: Dietmar P
authors.initials: DP
authors.lastname: Berger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000188:drug therapy*; D011961:Receptors, Fc / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D013926:Thrombopoietin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; D001374:Azacitidine