Long Term Use of Eltrombopag in Children with Chronic Immune Thrombocytopenia: Extended Real Life Retrospective Multicenter Experience of the Italian Association of Pediatric Hematology and Oncology

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2023 Jul 31

PMID 37521342

Authors

Paola Giordano

Giuseppe Lassandro

Angelica Barone

Simone Cesaro

Ilaria Fotzi

Fiorina Giona

Chiara Gorio

Angela Maggio

Maurizio Miano

Antonio Marzollo

Margherita Nardi

Andrea Pession

Antonio Ruggiero

Giovanna Russo

Paola Saracco

Marco Spinelli

Alessandra Tolva

Assunta Tornesello

Valentina Palladino

Giovanni Carlo Del Vecchio

Affiliations

Soon will be listed here.

Abstract

Background: The present multicenter retrospective study on eltrombopag administration in Italian children with chronic ITP aims to extend follow-up of our previous study.

Materials And Methods: This retrospective multicenter study was conducted in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). Patients were classified into three subgroups: group 1 included patients who discontinued treatment due to a stable platelet count; group 2 included patients who discontinued treatment due to ineffectiveness; group 3 included patients who did not permanently discontinue treatment.

Results: 56 patients were eligible for analysis. The median duration of eltrombopag treatment was 40 months (7-71 months). Twenty patients (36%) discontinued permanently eltrombopag. The reasons of permanent discontinuation were adverse effects ( = 1), inefficacy ( = 10), stable platelet count ( = 9). All patients of group 1 maintained a durable response without additional treatments after eltrombopag discontinuation. We found that patients of group 2 were on treatment for less time (median treatment time: 13.5 months, min: 6.0 - max: 56.0) than patients of group 1 (median treatment time: 34 months, min: 16.0 - max: 62.0) ( < 0.05). Patients of group 2 mostly did not achieve a stable platelet count in the first 6 months of treatment and underwent concomitant therapies during follow-up respect of group 1 and group 3 ( < 0.01).

Conclusion: Our study found that the benefits of eltrombopag treatment, in terms of platelet count improvement and use of additional therapies, are identifiable from the first 6 months of treatment.

References

Teekaput C, Nadsasarn A, Tanprawate S, Soontornpun A, Thiankhaw K, Wantaneeyawong C . Cerebral venous sinus thrombosis in immune thrombocytopenia patients treated with thrombopoietin receptor agonist: Case reports and literature review. Ann Med Surg (Lond). 2022; 79:104116. PMC: 9289509. DOI: 10.1016/j.amsu.2022.104116. View

Ruggeri M, Tosetto A, Palandri F, Polverelli N, Mazzucconi M, Santoro C . Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost. 2014; 12(8):1266-73. DOI: 10.1111/jth.12636. View

Provan D, Semple J . Recent advances in the mechanisms and treatment of immune thrombocytopenia. EBioMedicine. 2022; 76:103820. PMC: 8792416. DOI: 10.1016/j.ebiom.2022.103820. View

Cheng X, Fu L, Ma J, Gu H, Chen Z, Zhao L . Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice. Blood Adv. 2021; 5(19):3799-3806. PMC: 8679667. DOI: 10.1182/bloodadvances.2020004110. View

Ghadaki B, Nazi I, Kelton J, Arnold D . Sustained remissions of immune thrombocytopenia associated with the use of thrombopoietin receptor agonists. Transfusion. 2013; 53(11):2807-12. PMC: 3938454. DOI: 10.1111/trf.12139. View

Yozgat A, Leblebisatan G, Akbayram S, Cinar Ozel S, Karakas Z, Erduran E . Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children with Immune Thrombocytopenia in Turkey. Turk J Haematol. 2020; 37(3):139-144. PMC: 7463208. DOI: 10.4274/tjh.galenos.2020.2019.0380. View

Gonzalez-Lopez T, Pascual C, Alvarez-Roman M, Fernandez-Fuertes F, Sanchez-Gonzalez B, Caparros I . Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia. Am J Hematol. 2014; 90(3):E40-3. DOI: 10.1002/ajh.23900. View

Del Vecchio G, De Santis A, Accettura L, de Mattia D, Giordano P . Chronic immune thrombocytopenia in childhood. Blood Coagul Fibrinolysis. 2014; 25(4):297-9. DOI: 10.1097/MBC.0000000000000043. View

Rodeghiero F . Is ITP a thrombophilic disorder?. Am J Hematol. 2015; 91(1):39-45. DOI: 10.1002/ajh.24234. View

10.

Semple J, Rebetz J, Maouia A, Kapur R . An update on the pathophysiology of immune thrombocytopenia. Curr Opin Hematol. 2020; 27(6):423-429. DOI: 10.1097/MOH.0000000000000612. View

11.

Di Paola A, Palumbo G, Merli P, Argenziano M, Tortora C, Strocchio L . Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia. Int J Mol Sci. 2020; 22(1). PMC: 7796119. DOI: 10.3390/ijms22010097. View

12.

Giordano P, Lassandro G, Giona F, Jankovic M, Nardi M, Nobili B . ITP-QoL questionnaire for children with immune thrombocytopenia: Italian version validation's. Pediatr Hematol Oncol. 2014; 31(6):534-47. DOI: 10.3109/08880018.2014.915443. View

13.

Cheng G, Saleh M, Marcher C, Vasey S, Mayer B, Aivado M . Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2010; 377(9763):393-402. DOI: 10.1016/S0140-6736(10)60959-2. View

14.

Giordano P, Lassandro G, Valente M, Molinari A, Ierano P, Coppola A . Current management of the hemophilic child: a demanding interlocutor. Quality of life and adequate cost-efficacy analysis. Pediatr Hematol Oncol. 2014; 31(8):687-702. DOI: 10.3109/08880018.2014.930768. View

15.

Lassandro G, Palladino V, Vecchio G, Palmieri V, Corallo P, Faienza M . Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era. Endocr Metab Immune Disord Drug Targets. 2020; 21(3):397-406. DOI: 10.2174/1871530320666200531142244. View

16.

Lambert M, Witmer C, Kwiatkowski J . Therapy induced iron deficiency in children treated with eltrombopag for immune thrombocytopenia. Am J Hematol. 2017; 92(6):E88-E91. DOI: 10.1002/ajh.24705. View

17.

cervinek L, Mayer J, Doubek M . Sustained remission of chronic immune thrombocytopenia after discontinuation of treatment with thrombopoietin-receptor agonists in adults. Int J Hematol. 2015; 102(1):7-11. DOI: 10.1007/s12185-015-1793-1. View

18.

Mahevas M, Fain O, Ebbo M, Roudot-Thoraval F, Limal N, Khellaf M . 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(6):865-9. DOI: 10.1111/bjh.12888. View

19.

Singh A, Uzun G, Bakchoul T . Primary Immune Thrombocytopenia: Novel Insights into Pathophysiology and Disease Management. J Clin Med. 2021; 10(4). PMC: 7920457. DOI: 10.3390/jcm10040789. View

20.

Wong R, Saleh M, Khelif A, Salama A, Portella M, Burgess P . 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. DOI: 10.1182/blood-2017-04-748707. View