Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy.
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.
Kantarjian
Hagop M
HM
Leukemia Department, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. hkantarj@mdanderson.org
Giles
Francis J
FJ
Greenberg
Peter L
PL
Paquette
Ron L
RL
Wang
Eunice S
ES
Gabrilove
Janice L
JL
Garcia-Manero
Guillermo
G
Hu
Kuolung
K
Franklin
Janet L
JL
Berger
Dietmar P
DP
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*
D000964:Antimetabolites, Antineoplastic; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; D001374:Azacitidine