Thrombopoietin Receptor Agonists in Paediatric ITP Patients: Long Term Follow up Data in 34 Patients
Authors: Grainger John D. , Routledge David J M , Kruse Alexandra , Connor Philip , Sibson Keith , Biss Tina T , Bussel James B. 
Published: October 2019

Abstract
Introduction: Immune ThrombocytoPaenia (ITP) in children consists of an isolated thrombocytopaenia (platelet count less than 100 x 109/L) in the absence of any other identifiable cause (Rodeghiero 2009) and is a diagnosis of exclusion. The majority of children diagnosed with ITP remit in the first few months with approximately 30% going on to develop chronic ITP (Thrombocytopaenia persisting > 12 months) (Imbach 2006).
The majority of children with chronic ITP are managed supportively and do not require treatment. However, clinically significant bleeding may occur spontaneously or when challenged (e.g. infection, surgery, trauma). For patients who require frequent breakthrough treatment or in whom lifestyle restrictions are unacceptable, the treatment options are limited and the side effects often unacceptable to both families and physicians
Initial study reports suggest that thrombopoietin receptor agonists (TPO-RA) are effective and safe in paediatric patients, however longer term follow up data is unavailable Here we present follow-up data on the efficacy and safety on the use of TPO-RA in 34 paediatric patients with Chronic ITP across 5 tertiary referral centres with up to 5 years follow up.
Methods: A retrospective case note review was performed for paediatric patients with Chronic ITP who were treated with off-licence TPO-RA in 5 tertiary referral centres. Patients were initially treated on clinical study (PETIT n=25, PETIT2 n=2, or off study n=7).
Results: 34 patients (Female n=14, Male n=20) were identified who were treated with TPO-RA between 2009 and 2014. Median age when starting TPO-RA was 10 years of age (Range 2 to 17 years). 70% of patients were White, 12% Asian, 9% Arabic, 6% Hispanic and 3% Mixed ethnicity. Prior to starting TPO-RA all 34 patients had received at least one prior ITP therapy, with 41% receiving ≥3 previous ITP therapies (n=14). 71% had received steroids (n=24), 68% IVIG (n=23), 50% Rituximab (n=17), 27% Anti-D (n=9), 3% steroid sparing agents (n=1) and 3% had undergone splenectomy (n=1). 21% were on concurrent platelet rising therapy when starting TPO-RA (n=7). 97% started on TPO-RA for bleeding and/or thrombocytopaenia (n=33) and 3% started on TPO-RA for surgery (n=1).
During this period patients received treatment with Eltrombopag (n=28), Romiplostim (n=5) or both (n=1). Median duration of treatment with Eltrombopag was 30 months (range 6 to 55 months) and Romiplostim was 13 months (range 1 to 32 months). 32 patients were treated for ≥6 months, 28 for ≥1 year, 20 for ≥2 years and 4 for ≥4 years. Median maintenance dose for Eltrombopag was 0.94mg/kg and Romiplostim 7.92micrograms/kg).
53% of patients are still currently taking a TPO-RA (n=18). 1 patient who failed to respond to Eltrombopag, responded to Romiplostim. 50% of patients had a trial off treatment (n=17), with 4 patients remaining off treatment (Eltrombopag n=3, Romiplostim n=1). 4 patients stopped treatment due to the fear of potential side effects, 3 patients stopped treatment due to compliance issues, 4 patients stopped due to a lack of response to treatment and treatment was withdrawn in 1 patient due to subclinical (<grade 1) lens Opacities. 8 patients underwent bone marrow biopsy before and during/after treatment with TPO-RA. Of these 5 showed an increased reticulin grade after starting TPO-RA (Maximally Grade 1 to 2).
Conclusion: Our experience demonstrates that both Eltrombopag and Romiplostim are an effective treatment option in paediatric patients with chronic ITP. Both Eltrombopag and Romiplostim were well tolerated with exposures over 5 and 2 years respectively. 4 patients remain off treatment after a treatment ‘holiday’. Therefore withdrawal of treatment should be considered in all patients who are stable on treatment. No new safety concerns were identified but we would advocate continued surveillance.

Disclosures
Grainger: Amgen: Honoraria; Baxter: Honoraria, Research Funding; GlaxoSmithKline: Honoraria. Off Label Use: Eltrombopag is a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in adults with chronic ITP. Use in children and adolescents will be discussed.. Bussel:Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Honoraria; Novartis: Honoraria; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; IgG of America: Research Funding; GlaxoSmithKline: Equity Ownership, Honoraria, Research Funding; Genzyme: Research Funding; Eisai, Inc.: Research Funding; Cangene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Symphogen: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding.