Use of Eltrombopag after Romiplostim in Primary ITP Patients
Authors: González-López Tomás José , Pascual Cristina , Álvarez-Román María Teresa , Fernández-Fuentes Fernando , Sánchez-González Blanca , Caparrós Isabel , Jarque Isidro , Mingot María Eva , Hernández-Rivas José Angel , Martín-Salces Mónica , Solán Laura , Beneit Paola , Jiménez Reyes , Bernat Silvia , Andrade Marcio M. , Cortés Montserrat , Cortti María José , Pérez-Crespo Susana , Gómez-Núñez Marta , Olivera Pavel E. , Pérez-Rus Gloria , Martínez-Robles Violeta , Alonso Rafael , Fernández-Rodríguez Angeles , Arratibel María Carmen , Perera María , Fernández-Miñano Carmen , Fuertes-Palacio Miguel Angel , Vázquez-Paganini Juan Andrés , Juárez-Salcedo Luis Miguel , Valcarce Inés , Díaz-Gálvez Francisco Javier , Sainz Adriana , Fisac Rosa , Aguilar Carlos , Martínez-Badas María Paz , Peñarrubia María Jesús , García-Frade Javier , Calbacho Maria , de Cos Carmen , González-Silva Manuel , Coria Erika , Alonso Arancha , Casaus Alberto , Luaña Armando , Galán Pilar , Fernández-Canal Cristina , González-Porras José Ramón 
Published: November 2019

Abstract
Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP.
Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee.
Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%.
Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag.

Disclosures
No relevant conflicts of interest to declare.