Update on the Use of Thrombopoietin-Receptor Agonists in Pediatrics

Abstract

This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or MYH9-associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.

Zusammenfassung

Diese Übersicht fasst die Rationale und aktuellen Daten zur Anwendung von Thrombopoietin-Rezeptor-Agonisten (TPO-RAs) bei der Behandlung schwerer Thrombozytopenien bei Kindern und Jugendlichen zusammen. Der Fokus liegt auf Substanzen, die von der U.S. Food and Drug Administration (FDA) und der European Medicines Agency (EMA) für pädiatrische Patienten zugelassen wurden. Romiplostim und Eltrombopag sind bereits als Zweitlinientherapie für die chronische immunvermittelte Thrombozytopenie (ITP) etabliert. Wie bei Erwachsenen wird die Anwendung von TPO-RAs auch bei schwerer aplastischer Anämie (SAA), Chemotherapie-induzierter Thrombozytopenie (CIT), myelodysplastischem Syndromen (MDS) und unzureichender Megakaryopoiese nach hämatopoietischer Stammzelltransplantation bei pädiatrischen Patienten untersucht. Darüber hinaus verdienen Studien zur Bedeutung von TPO-RA bei der Behandlung seltener erblicher Thrombozytopenien, wie dem Wiskott-Aldrich-Syndrom (WAS), der kongenitalen amegakaryozytären Thrombozytopenie (CAMT) oder der MYH9-assoziierten Thrombozytopenie Aufmerksamkeit. Aktuelle Entwicklungen umfassen randomisierte kontrollierte Studien zur Anwendung von Avatrombopag und Lusutrombopag, die bei erwachsenen Patienten bereits zur Behandlung von mit chronischer Lebererkrankung (CLD) assoziierter Thrombozytopenie zugelassen sind. Basierend auf den aktuellen klinischen Erfahrungen und Studienergebnissen erwarten wir auch bei Kindern und Jugendlichen zukünftig eine Anwendung von TPO-RAs als „first-line“ Medikation bei primärer ITP, wobei die immunmodulatorischen Effekte und die Rate einer anhaltenden Remission nach Therapiebeendigung von besonderem Interesse sind, sowie eine selektive Anwendung von TPO-RAs bei Kindern und Jugendlichen mit seltenen angeborenen Thrombozytopenien.

Keywords

avatrombopag - eltrombopag - lusutrombopag - romiplostim - thrombopoietin - thrombopoietin receptor - thrombopoietin receptor agonist - thrombocytopenia - platelet count

Schlüsselwörter

Avatrombopag - Eltrombopag - Lusutrombopag - Romiplostim - Thrombopoietin - Thrombopoietin Rezeptor - Thrombozyten - Thrombozytopenie

Publication History

Received: 03 August 2023

Accepted: 16 January 2024

Article published online:
26 June 2024

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