Page 185 - 2019_11 Resto del Mondo-web

Romiplostim in pediatric ITP
maintain platelet counts in a hemostatic range, with median platelets >50-100x109/L; very few patients left the study because of AE or treatment failure. Development of treatment-free response in almost one- quarter of patients suggests that maintenance with romi- plostim in children will not always be a “life-long treat- ment.” The continued, steady development of treatment- free response in patients treated for three or more years is encouraging as well. Additional studies in larger num- bers of patients may further clarify some of the issues discussed in this study.
Acknowledgments
Susanna Mac, a medical writer from Amgen Inc., assisted the authors with drafting the manuscript and revised the manuscript based on extensive guidance from the authors. We would also like to thank all of the investigators, study staff, and patients who were part of this study. A full list of investigators is in Online Supplementary Table S4.
Funding
This study (NCT01071954; Amgen #20090340) and all analyses were funded by Amgen Inc.
References
1. Nugent D, McMillan R, Nichol JL, Slichter SJ. Pathogenesis of chronic immune throm- bocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146(6):585-596.
2. Cooper N. A review of the management of childhood immune thrombocytopenia: how can we provide an evidence-based approach? Br J Haematol. 2014;165(6):756- 767.
3. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88(1):3-40.
4. Psaila B, Petrovic A, Page LK, Menell J, Schonholz M, Bussel JB. Intracranial hemor- rhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases. Blood. 2009;114(23):4777-4783.
5. Schifferli A, Holbro A, Chitlur M, et al. A comparative prospective observational study of children and adults with immune thrombocytopenia: 2-year follow-up. Am J Hematol. 2018;93(6):751-759.
6. Chotsampancharoen T, Sripornsawan P, Duangchoo S, Wongchanchailert M, McNeil E. Clinical outcome of childhood chronic immune thrombocytopenia: A 38-year experience from a single tertiary center in Thailand. Pediatr Blood Cancer. 2017;64(11): e26598.
7. Bussel JB, de Miguel PG, Despotovic JM, et al. Eltrombopag for the treatment of chil- dren with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015;2(8):e315-325.
8. Grainger JD, Locatelli F, Chotsampancharoen T, et al. Eltrombopag for children with chronic immune thrombo- cytopenia (PETIT2): a randomised, multi- centre, placebo-controlled trial. Lancet. 2015;386(10004):1649-1658.
9. BusselJB,BuchananGR,NugentDJ,etal.A randomized, double-blind study of romi- plostim to determine its safety and efficacy in children with immune thrombocytope- nia. Blood. 2011;118(1):28-36.
10. Tarantino MD, Bussel JB, Blanchette VS, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10039):45-54.
11. Bussel JB, Hsieh L, Buchanan GR, et al.
Long-term use of the thrombopoietin- mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP). Pediatr Blood Cancer. 2015;62(2):208-213.
12. Cines DB, Wasser J, Rodeghiero F, et al. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocy- topenia. Haematologica. 2017;102(8):1342- 1351.
13. Bansal D, Bhamare TA, Trehan A, Ahluwalia J, Varma N, Marwaha RK. Outcome of chronic idiopathic thrombocy- topenic purpura in children. Pediatr Blood Cancer. 2010;54(3):403-407.
14. Bennett CM, Neunert C, Grace RF, et al. Predictors of remission in children with newly diagnosed immune thrombocytope- nia: Data from the Intercontinental Cooperative ITP Study Group Registry II participants. Pediatr Blood Cancer. 2018;65 (1):e26818.
15. Evim MS, Baytan B, Gunes AM. Childhood immune thrombocytopenia: Long-term fol- low-up data evaluated by the criteria of the international working group on immune thrombocytopenic purpura. Turk J Haematol. 2014;31(1):32-39.
16. Kim CY, Lee EH, Yoon HS. High remission rate of chronic immune thrombocytopenia in children: Result of 20-year follow-up. Yonsei Med J. 2016;57(1):127-131.
imab therapy in children and adults with immune thrombocytopenia. Blood. 2012; 119(25):5989-5995.
22. Bao W, Bussel JB, Heck S, et al. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood. 2010;116(22):4639-4645.
23. Chong BH. ITP: Tregs come to the rescue. Blood. 2010;116(22):4388-4390.
24. Johansson U, Macey MG, Kenny D, Provan AB, Newland AC. The role of natural killer T (NKT) cells in immune thrombocytope- nia: is strong in vitro NKT cell activity relat- ed to the development of remission? Br J Haematol. 2005;129(4):564-565.
25. Li X, Zhong H, Bao W, et al. Defective regu- latory B-cell compartment in patients with immune thrombocytopenia. Blood. 2012; 120(16):3318-3325.
26. Liu XG, Liu S, Feng Q, et al. Thrombopoietin receptor agonists shift the balance of Fcgamma receptors toward inhibitory receptor IIb on monocytes in ITP. Blood. 2016;128(6):852-861.
27. Grainger JD, Routledge DJM, Kruse A, et al. Thrombopoietin receptor agonists in paedi- atric ITP patients: Long term follow up data in 34 patients [abstract]. Blood. 2014;124(21):4206.
28. Bussel JB, Wang X, Lopez A, Eisen M. Case study of remission in adults with immune thrombocytopenia following cessation of treatment with the thrombopoietin mimetic romiplostim. Hematology. 2016;21(4):257-
17. Revel-Vilk S, Yacobovich J, Frank S, et al.
Age and duration of bleeding symptoms at
diagnosis best predict resolution of child-
hood immune thrombocytopenia at 3, 6, 262.
and 12 months. J Pediatr. 2013;163(5):1335-
1339 e1331-1332.
18. Rosthøj S, Rajantie J, Treutiger I, et al.
Duration and morbidity of chronic immune thrombocytopenic purpura in children: five- year follow-up of a Nordic cohort. Acta Paediatr. 2012;101(7):761-766.
19. Imbach P, Kühne T, Müller D, et al. Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS). Pediatr Blood Cancer. 2006;46(3):351-356.
20. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombo- cytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.
21. Patel VL, Mahevas M, Lee SY, et al. Outcomes 5 years after response to ritux-
29. Mahevas M, Fain O, Ebbo M, et al. The tem- porary use of thrombopoietin-receptor ago- nists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Haematol. 2014;165(6):865-869.
30. Newland A, Godeau B, Priego V, et al. Remission and platelet responses with romi- plostim in primary immune thrombocy- topenia: final results from a phase 2 study. Br J Haematol. 2016;172(2):262-273.
31. Kuter DJ, Bussel JB, Newland A, et al. Long- term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161(3):411-423.
32. Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(23):2527-2536.
haematologica | 2019; 104(11)
2291