Thrombopoietin receptor agonist switch in adult primary immune thrombocytopenia patients: A retrospective collaborative survey involving 4 Spanish centres.

To describe the reasons for and result of thrombopoietin receptor agonists (TPO-RA) switching in adult immune thrombocytopenia (ITP) patients of 4 Spanish centres. We retrospectively analysed all patients who received sequential treatment with both TPO-RA between 2010 and 2015 recording clinical and biological parameters. Twenty-six patients were included; 17 received first romiplostim and 9 received first eltrombopag. Reasons for switching were inefficacy (n = 10), patient preference (n = 8), side effects (n = 5) and excessive platelet count fluctuation (n = 3). When the switch was due to inefficacy, 100% of patients who received romiplostim first and 66% who received eltrombopag first responded to the second drug. It is significant that none of the patients who received romiplostim first reached the maximum recommended dose before switching. When the change was due to patient preference or because of side effects, 100% of the patients responded to both TPO-RA. Three patients changed from romiplostim to eltrombopag due to platelet count fluctuation; one did not respond and the fluctuation persisted in the remaining 2 patients. We also found 4 sustained remissions after administering the second TPO-RA, 2 of these with inefficacy of the first drug. TPO-RA switching is a feasible strategy in different scenarios with high probability of success.

Lakhwani S ，Perera M ，Fernández-Fuertes F ，Ríos de Paz MA ，Torres M ，Raya JM ，Hernández MT ... -  《-》

Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia (ITP) switched to eltrombopag or romiplostim.

Kuter DJ ，Macahilig C ，Grotzinger KM ，Poston SA ，Wang PF ，Dawson KL ，Ward M ... -  《-》

Thrombopoietin receptor agonists in refractory immune thrombocytopenia: differential responses to eltrombopag and romiplostim: a case report and possible explanations.

Although new thrombopoietin (TPO) receptor agonist drugs, such as romiplostim and eltrombopag, are highly effective and well tolerated for patients with immune thrombocytopenia (ITP) refractory to first-line treatments such as prednisolone, the cross-resistance of these two TPO receptor agonists is still unknown. An 84-year-old Japanese female patient with steroid-refractory ITP received eltrombopag with a gradually increasing dose schedule from 12.5 to 25 mg/day, 37.5 mg/day and finally 50 mg/day. As no increase in platelet count was observed even at the maximum dose of 50 mg/day, and eltrombopag-related grade 3 elevation of aspartate aminotransferase was observed, another TPO receptor agonist, romiplostim, was administered at 1 μg/kg/week subcutaneously. A rapid increase in platelet count was observed 1 week after the first injection. The dose of romiplostim was escalated to 4 μg/kg according to the platelet count and a complete response was achieved 7 weeks after the first injection without any adverse events. The successful treatment of ITP refractory to eltrombopag with romiplostim strongly suggests that the absence of cross-resistance between these two approved TPO receptor agonists and possible differences in mechanism of action. Further study of the mechanisms of action of TPO receptor agonists is called for along with further exploration of the potential of romiplostim in refractory ITP.

Aoki T ，Harada Y ，Matsubara E ，Suzuki T ，Oyama T ，Kasai M ，Uchida T ，Ogura M ... -  《-》

Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study.

In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri-operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty-one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO-RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty-four patients (77%) responded to the use of TPO-RAs with a median platelet count that increased from 11 × 10(9) /L before starting TPO-RAs to 114 × 10(9) /L pre-splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty-nine patients underwent splenectomy while two patients who responded to TPO-RAs subsequently refused surgery. Post-splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 × 10(9) /L, respectively and one Grade 3 infectious event. TPO-RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri-operative complications in ITP candidates to splenectomy. An increased risk of post-splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low-molecular weight heparin is generally recommended.

Zaja F ，Barcellini W ，Cantoni S ，Carpenedo M ，Caparrotti G ，Carrai V ，Di Renzo N ，Santoro C ，Di Nicola M ，Veneri D ，Simonetti F ，Liberati AM ，Ferla V ，Paoloni F ，Crea E ，Volpetti S ，Tuniz E ，Fanin R ... -  《-》

Use of eltrombopag after romiplostim in primary immune thrombocytopenia.

The thrombopoietin receptor agonists (THPO-RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO-RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18-83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5-21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet-count fluctuation (n = 6) and side-effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow-up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet-count fluctuation and side-effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.

González-Porras JR ，Mingot-Castellano ME ，Andrade MM ，Alonso R ，Caparrós I ，Arratibel MC ，Fernández-Fuertes F ，Cortti MJ ，Pascual C ，Sánchez-González B ，Bernat S ，Fuertes-Palacio MA ，Vázquez-Paganini JA ，Olivera PE ，Alvarez-Román MT ，Jarque I ，Cortés M ，Martínez-Robles V ，Díaz-Gálvez FJ ，Calbacho M ，Fernández-Miñano C ，Garcia-Frade J ，González-López TJ ... -  《-》