A Single-Arm, Long-Term Efficacy and Safety Study of Subcutaneous Romiplostim in Children with Immune Thrombocytopenia.

Romiplostim is a thrombopoietin receptor agonist approved for children/adults with immune thrombocytopenia (ITP) for >/=6 months, recommended as second-line treatment. This phase 3b, single-arm, multicenter study investigated long term efficacy/safety of romiplostim in children >/=1-<18 years old with >/=6 months ITP duration and platelet counts </=30×109/L. Children received weekly subcutaneous romiplostim (1 μg/kg titrated to 10 μg/kg) to maintain platelets within 50-200×109/L. A subset underwent bone marrow examinations. Primary endpoint was percent of time with platelet response during the first 6 months' treatment (counts >/=50×109/L without rescue medication within the preceding 4 weeks). Overall, 203 patients (median age, 10.0 years) received >/=1 dose of romiplostim, median treatment duration was approximately 3 years, median average weekly dose was 6.9 μg/kg. Ninety-five (46.8%) discontinued (lack of efficacy, n=43 [21.2%]). Platelet responses were achieved a median (IQR) of 50.0% (16.7%-83.3%) of the time during the first 6 months, increasing to 78.2% (26.7%-90.4%) during the overall 36 month treatment period. Eleven patients (5.4%) achieved sustained responses (consecutive counts >/=50×109/L without ITP medications for >/=24 weeks). Treatment-related adverse events (AEs) occurred in 56 patients (27.6%), with 8 (3.9%) experiencing serious treatment-related AEs; all of these led to discontinuation, including 4 cases of neutralizing antibodies (romiplostim, n=3; thrombopoietin, n=1). Bleeding occurred in 141 patients (69.5%), decreasing over time; grade >/=3 bleeding events occurred in 20 (9.9%). At year 2, 8/63 evaluable patients (12.7%) had grade 2 reticulin. Long-term romiplostim resulted in sustained on-treatment platelet responses with an overall safety profile consistent with previous studies.