Skip to main content
Top
Published in: International Journal of Hematology 1/2016

01-01-2016 | Original Article

Multicenter, prospective study to evaluate the efficacy of biweekly romiplostim administration in patients with immune thrombocytopenia

Authors: Silvia Park, Sung Soo Yoon, Jung Hee Lee, Joon Seong Park, Jun Ho Jang, Jong Wook Lee

Published in: International Journal of Hematology | Issue 1/2016

Login to get access

Abstract

Multicenter, prospective study was conducted to evaluate the efficacy of biweekly romiplostim in maintaining platelet ≥30 × 109/L for at least 4 weeks. Treatment was started with a weekly injection (1 mcg/kg), and the dose was escalated until a titrated dose was achieved that maintained a platelet 50–200 × 109/L for four consecutive weeks. Patients were scheduled to a biweekly schedule, and returned to a weekly schedule if platelets fell to <30 × 109/L. Eighteen patients were enrolled (median platelet, 14 × 109/L). After the first weekly schedule, ten of eighteen (55.6 %) attained a median titrated dose of 3 mcg/kg and proceeded to the first biweekly schedule. However, all failed to maintain a platelet ≥30 × 109/L for at least 4 weeks, and returned to a second weekly schedule, where eight of the ten achieved a titrated dose (median, 5 mcg/kg) and moved to a second schedule of biweekly romiplostim. Three of the eight (37.5 %) showed platelet ≥30 × 109/L for 4, 8, and 10 weeks, but all eight patients eventually experienced a drop in platelets. Lengthening the dose interval of romiplostim to greater than a week is not feasible to maintain stable platelet count.
Literature
1.
2.
go back to reference Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386–93.PubMedCrossRef Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386–93.PubMedCrossRef
3.
go back to reference Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999;94:909–13.PubMed Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999;94:909–13.PubMed
4.
go back to reference Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol. 2003;122:966–74.PubMedCrossRef Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol. 2003;122:966–74.PubMedCrossRef
5.
go back to reference Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost. 2006;4:2377–83.PubMedCrossRef Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost. 2006;4:2377–83.PubMedCrossRef
6.
go back to reference McMillan R. The pathogenesis of chronic immune thrombocytopenic purpura. Semin Hematol. 2007;44:S3–11.PubMedCrossRef McMillan R. The pathogenesis of chronic immune thrombocytopenic purpura. Semin Hematol. 2007;44:S3–11.PubMedCrossRef
7.
go back to reference Cines DB, McMillan R. Pathogenesis of chronic immune thrombocytopenic purpura. Curr Opin Hematol. 2007;14:511–4.PubMedCrossRef Cines DB, McMillan R. Pathogenesis of chronic immune thrombocytopenic purpura. Curr Opin Hematol. 2007;14:511–4.PubMedCrossRef
8.
go back to reference McMillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura. Semin Hematol. 2000;37:239–48.PubMedCrossRef McMillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura. Semin Hematol. 2000;37:239–48.PubMedCrossRef
10.
go back to reference Lakshmanan S, Cuker A. Contemporary management of primary immune thrombocytopenia in adults. J Thromb Haemost. 2012;10:1988–98.PubMedCrossRef Lakshmanan S, Cuker A. Contemporary management of primary immune thrombocytopenia in adults. J Thromb Haemost. 2012;10:1988–98.PubMedCrossRef
11.
go back to reference Louwes H. Zeinali Lathori OA, Vellenga E, de Wolf JT. Platelet kinetic studies in patients with idiopathic thrombocytopenic purpura. Am J Med. 1999;106:430–4.PubMedCrossRef Louwes H. Zeinali Lathori OA, Vellenga E, de Wolf JT. Platelet kinetic studies in patients with idiopathic thrombocytopenic purpura. Am J Med. 1999;106:430–4.PubMedCrossRef
12.
go back to reference Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80:33–40.PubMedPubMedCentralCrossRef Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80:33–40.PubMedPubMedCentralCrossRef
13.
go back to reference McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood. 2004;103:1364–9.PubMedCrossRef McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood. 2004;103:1364–9.PubMedCrossRef
14.
go back to reference Houwerzijl EJ, Blom NR, van der Want JJ, Esselink MT, Koornstra JJ, Smit JW, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103:500–6.PubMedCrossRef Houwerzijl EJ, Blom NR, van der Want JJ, Esselink MT, Koornstra JJ, Smit JW, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103:500–6.PubMedCrossRef
15.
go back to reference Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. Blood. 1946;1:27–50.PubMed Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. Blood. 1946;1:27–50.PubMed
16.
go back to reference Nugent D, McMillan R, Nichol JL, Slichter SJ. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146:585–96.PubMedCrossRef Nugent D, McMillan R, Nichol JL, Slichter SJ. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146:585–96.PubMedCrossRef
17.
go back to reference Pisciotta AV, Stefanini M, Dameshek W. Studies on platelets. X. Morphologic characteristics of megakaryocytes by phase contrast microscopy in normals and in patients with idiopathic thrombocytopenic purpura. Blood. 1953;8:703–23.PubMed Pisciotta AV, Stefanini M, Dameshek W. Studies on platelets. X. Morphologic characteristics of megakaryocytes by phase contrast microscopy in normals and in patients with idiopathic thrombocytopenic purpura. Blood. 1953;8:703–23.PubMed
18.
go back to reference Branehog I, Kutti J, Ridell B, Swolin B, Weinfeld A. The relation of thrombokinetics to bone marrow megakaryocytes in idiopathic thrombocytopenic purpura (ITP). Blood. 1975;45:551–62.PubMed Branehog I, Kutti J, Ridell B, Swolin B, Weinfeld A. The relation of thrombokinetics to bone marrow megakaryocytes in idiopathic thrombocytopenic purpura (ITP). Blood. 1975;45:551–62.PubMed
19.
go back to reference Stoll D, Cines DB, Aster RH, Murphy S. Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia. Blood. 1985;65:584–8.PubMed Stoll D, Cines DB, Aster RH, Murphy S. Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia. Blood. 1985;65:584–8.PubMed
20.
go back to reference Nomura S, Dan K, Hotta T, Fujimura K, Ikeda Y. Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura. Blood. 2002;100:728–30.PubMedCrossRef Nomura S, Dan K, Hotta T, Fujimura K, Ikeda Y. Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura. Blood. 2002;100:728–30.PubMedCrossRef
21.
go back to reference Perreault S, Burzynski J. Romiplostim: a novel thrombopoiesis-stimulating agent. Am J Health Syst Pharm. 2009;66:817–24.PubMedCrossRef Perreault S, Burzynski J. Romiplostim: a novel thrombopoiesis-stimulating agent. Am J Health Syst Pharm. 2009;66:817–24.PubMedCrossRef
22.
go back to reference Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395–403.PubMedCrossRef Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395–403.PubMedCrossRef
23.
go back to reference Broudy VC, Lin NL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine. 2004;25:52–60.PubMedCrossRef Broudy VC, Lin NL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine. 2004;25:52–60.PubMedCrossRef
24.
go back to reference Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355:1672–81.PubMedCrossRef Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355:1672–81.PubMedCrossRef
25.
go back to reference Amgen Europe B.V. Summary of product characteristics 2009. Breda, The Netherlands: Amgen Europe B.V.; 2009. Amgen Europe B.V. Summary of product characteristics 2009. Breda, The Netherlands: Amgen Europe B.V.; 2009.
26.
go back to reference Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004;76:628–38.PubMedCrossRef Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004;76:628–38.PubMedCrossRef
27.
go back to reference Kumagai Y, Fujita T, Ozaki M, Sahashi K, Ohkura M, Ohtsu T, et al. Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. J Clin Pharmacol. 2007;47:1489–97.PubMedCrossRef Kumagai Y, Fujita T, Ozaki M, Sahashi K, Ohkura M, Ohtsu T, et al. Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. J Clin Pharmacol. 2007;47:1489–97.PubMedCrossRef
28.
go back to reference Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.PubMedCrossRef Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.PubMedCrossRef
29.
go back to reference Wang YM, Krzyzanski W, Doshi S, Xiao JJ, Perez-Ruixo JJ, Chow AT. Pharmacodynamics-mediated drug disposition (PDMDD) and precursor pool lifespan model for single dose of romiplostim in healthy subjects. AAPS J. 2010;12:729–40.PubMedPubMedCentralCrossRef Wang YM, Krzyzanski W, Doshi S, Xiao JJ, Perez-Ruixo JJ, Chow AT. Pharmacodynamics-mediated drug disposition (PDMDD) and precursor pool lifespan model for single dose of romiplostim in healthy subjects. AAPS J. 2010;12:729–40.PubMedPubMedCentralCrossRef
30.
go back to reference Cao Y, Jusko WJ. Incorporating target-mediated drug disposition in a minimal physiologically-based pharmacokinetic model for monoclonal antibodies. J Pharmacokinet Pharmacodyn. 2014;41:375–87.PubMedPubMedCentralCrossRef Cao Y, Jusko WJ. Incorporating target-mediated drug disposition in a minimal physiologically-based pharmacokinetic model for monoclonal antibodies. J Pharmacokinet Pharmacodyn. 2014;41:375–87.PubMedPubMedCentralCrossRef
31.
go back to reference Li J, Xia Y, Kuter DJ. Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics. Br J Haematol. 1999;106:345–56.PubMedCrossRef Li J, Xia Y, Kuter DJ. Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics. Br J Haematol. 1999;106:345–56.PubMedCrossRef
32.
go back to reference Broudy VC, Lin NL, Sabath DF, Papayannopoulou T, Kaushansky K. Human platelets display high-affinity receptors for thrombopoietin. Blood. 1997;89:1896–904.PubMed Broudy VC, Lin NL, Sabath DF, Papayannopoulou T, Kaushansky K. Human platelets display high-affinity receptors for thrombopoietin. Blood. 1997;89:1896–904.PubMed
33.
go back to reference Mager DE, Jusko WJ. General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. J Pharmacokinet Pharmacodyn. 2001;28:507–32.PubMedCrossRef Mager DE, Jusko WJ. General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. J Pharmacokinet Pharmacodyn. 2001;28:507–32.PubMedCrossRef
34.
go back to reference Cronkite EP, Bond VP, Fliedner TM. Studies on the origin, production and destruction of platelets. In: Johnson SA, W. MR, Rebuck JW, Horn RC editors. Blood Platelets. Boston: Little, Brown; 1961. Cronkite EP, Bond VP, Fliedner TM. Studies on the origin, production and destruction of platelets. In: Johnson SA, W. MR, Rebuck JW, Horn RC editors. Blood Platelets. Boston: Little, Brown; 1961.
35.
go back to reference Jackson CW, Arnold JT, Pestina TI, Stenberg PE. Megakaryocyte biology. In: Kuter D, Hunt P, Sheridan WP, Zucker-Franklin D, editors. Thrombopoiesis and thrombopoietins. Totowa: Humana; 1997. Jackson CW, Arnold JT, Pestina TI, Stenberg PE. Megakaryocyte biology. In: Kuter D, Hunt P, Sheridan WP, Zucker-Franklin D, editors. Thrombopoiesis and thrombopoietins. Totowa: Humana; 1997.
36.
go back to reference Harker LA, Roskos LK, Marzec UM, Carter RA, Cherry JK, Sundell B, et al. Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers. Blood. 2000;95:2514–22.PubMed Harker LA, Roskos LK, Marzec UM, Carter RA, Cherry JK, Sundell B, et al. Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers. Blood. 2000;95:2514–22.PubMed
37.
go back to reference Mahevas M, Fain O, Ebbo M, Roudot-Thoraval F, Limal N, Khellaf M, et al. The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Haematol. 2014;165:865–9.PubMedCrossRef Mahevas M, Fain O, Ebbo M, Roudot-Thoraval F, Limal N, Khellaf M, et al. The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Haematol. 2014;165:865–9.PubMedCrossRef
38.
go back to reference Bussel JB, Wang X, Eisen M. Case studies of remission in adults with immune thrombocytopenia (ITP) following cessation of treatment with the TPO receptor agonist romiplostim. 55th ASH Annual Meeting and Exposition. New Orleans, LA; 2013:Abstract 328. 2013. Bussel JB, Wang X, Eisen M. Case studies of remission in adults with immune thrombocytopenia (ITP) following cessation of treatment with the TPO receptor agonist romiplostim. 55th ASH Annual Meeting and Exposition. New Orleans, LA; 2013:Abstract 328. 2013.
Metadata
Title
Multicenter, prospective study to evaluate the efficacy of biweekly romiplostim administration in patients with immune thrombocytopenia
Authors
Silvia Park
Sung Soo Yoon
Jung Hee Lee
Joon Seong Park
Jun Ho Jang
Jong Wook Lee
Publication date
01-01-2016
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 1/2016
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-015-1889-7

Other articles of this Issue 1/2016

International Journal of Hematology 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine