Long-Term Use of Open-Label Romiplostim in Children with Chronic/Refractory Immune Thrombocytopenia (ITP)

Abstract 621 Background: Treatment options for children with chronic/refractory ITP are not well characterized. In a phase 1/2 16-week randomized double-blind placebo-controlled study of 22 patients (romiplostim n = 17, placebo n = 5), the thrombopoietin (TPO) receptor agonist romiplostim was well tolerated and 15 of 17 romiplostim-treated patients achieved platelet counts ≥50×10 9 /L (Bussel et al, Blood 2011). Twenty-one of 22 patients from this phase 1/2 study subsequently entered an open-label extension study; 1/21 patients discontinued the extension study before receiving romiplostim. For the 20 patients who received romiplostim in the first extension study, the mean duration of treatment was 1.6 years (range, 0.1 to 2.1 years); all 20 achieved platelet counts >50×10 9 /L (Nugent et al, 2011 ASPHO abstracts). Of the 17 patients who completed this extension study, 12 rolled over into a second open-label extension study for up to 2.5 years of further romiplostim treatment. Results from those 12 patients are described here. Objective: To investigate the safety and efficacy of long-term use of romiplostim in pediatric ITP. Methods: During the second extension study, patients received weekly subcutaneous injections of romiplostim with the initial dose being the same as the last dose in the prior study. Dose adjustment was allowed to maintain platelet counts in the target range of 50–200×10 9 /L. The maximum allowed romiplostim dose was 10 μg/kg. The primary endpoint of this study was incidence of adverse events; platelet response was a secondary endpoint. The protocol did not require bone marrow biopsies to be conducted at pre-defined intervals, but any bone marrow biopsies performed as clinically indicated were to be analyzed. As deemed appropriate by investigators, patients or their caregivers had the option to administer romiplostim at home during this study; those patients who administered romiplostim at home used diary cards to record dosing date, time, volume administered, and any dosing errors. Patients who turned 18 years of age during this study were permitted to remain on study. Results: Baseline demographics for this second extension study included a median age of 12 years (range 3, 16 years), 67% male, and 33% with a prior splenectomy. Median romiplostim treatment duration in this second extension study was 118.9 weeks (range 100.1, 125.9 weeks); median average weekly romiplostim dose was 5.2 μg/kg (range 1, 10 μg/kg). Of the 3 patients who discontinued the study, 2 withdrew consent and 1 was noncompliant; no patients withdrew due to safety issues and 9 continued on study. Median platelet counts for all 12 patients were above 50×10 9 /L throughout, and were in the target range of 50–200×10 9 /L for all visits but Weeks 3 and 76 (Figure). Interestingly, the median dose decreased over time from a median (Q1, Q3) of 8.0 (5.5, 9.0) μg/kg at Week 1 to 1.0 (0.0, 6.0) μg/kg at Week 116 (last timepoint for which data are available) (Figure). Two patients received rescue medications (defined as medications used for platelet counts 9 /L, bleeding/wet purpura, or investigator decision); one patient received platelet transfusions and another prednisone. Four patients (33.3%) had serious adverse events (asthma, epistaxis, hemangioma, hypotension, pyrexia, thrombocytopenia, and transfusion reaction) and one had a life-threatening adverse event (thrombocytopenia). None of the adverse events were deemed treatment-related by the investigators. There were no fatal adverse events. Eight patients had bleeding adverse events; one of which (gingival bleeding) was deemed treatment-related. These bleeding adverse events included epistaxis (4 patients), petechiae (3 patients), gingival bleeding (2 patients), and (in 1 patient each) bleeding from the anus, injection site, lip, and mouth; 1 patient also had unspecified bleeding. No bone marrow biopsies were reported to have been performed. Conclusion: In this open-label extension study, romiplostim increased platelet counts in pediatric patients with chronic ITP without significant toxicity. Thus, romiplostim has been well tolerated and shown to be of clinical benefit to pediatric patients with refractory severe chronic ITP. As this study is ongoing, future results will provide additional data regarding even longer-term use of TPO receptor agonists in this patient population. Disclosures: Bussel: Cangene: Research Funding; GlaxoSmithKline: Family owns GSK stock, Family owns GSK stock Other, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Portola: Consultancy; Amgen: Family owns Amgen stock Other, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Off Label Use: The use of romiplostim in pediatric patients was examined in this study. Nie: Amgen: Employment, Equity Ownership. Eisen: Amgen: Employment, Equity Ownership.