Most pediatric patients with immune thrombocytopenia had rapid and durable platelet responses when treated with the thrombopoietin fusion protein analog romiplostim.
Michael D. Tarantino, MD
Most pediatric patients with immune thrombocytopenia (ITP) had rapid and durable platelet responses when treated with the thrombopoietin fusion protein analog romiplostim (Nplate), according to integrated data from 5 clinical trials that were presented at the 2018 ASH Annual Meeting.
Nearly 90% of 282 evaluable patients had platelet responses, which occurred after a median treatment duration of 6 weeks. Patients remained in response for a median of 76% of months during follow-up.
In general, romiplostim was well tolerated; 3% of patients discontinued treatment because of adverse events (AEs), Michael D. Tarantino, MD, of the Bleeding & Clotting Disorders Institute, reported during the meeting.
“Nineteen patients maintained treatment-free responses for at least 6 months after discontinuing all ITP treatment,” Tarantino said in a poster presentation of the data. “These treatment-free responses lasted a median of 12 months. There were no clear differences in patient characteristics between those with and without a treatment-free response.”
Romiplostim has FDA approval for treatment of adult patients with ITP, and the European Union has approved the agent for treating patients 1 year of age and older who are refractory to other treatments. However, more data are required to confirm the safety and efficacy of romiplostim in children and clarify its role in the management of the condition.
The findings from 5 clinical trials of children with ITP treated with romiplostim included randomized and placebo-controlled trials, single-arm trials, open-label trials, and extension studies. The 282 children included in the analysis had a median age of 10, median ITP duration of 1.9 years, and median baseline platelet count of 14.3 x 109/L.
The patients received a median of 2 prior ITP therapies before initiating romiplostim, and 46% of patients had 3 or more prior treatments. Treatment history most often included corticosteroids (88%), intravenous immunoglobulin (87%), anti-D antibody (23%), and rituximab (Rituxan; 21%).
Patients began romiplostim treatment at a dose of 1 µg/kg weekly, titrated to a maximum dose of 10 µg/kg weekly as needed to maintain a platelet count of 50,000 to 200,000/mL. The 282 patients had a median treatment duration of 65 weeks, including 62% of patients treated for at least 48 weeks, and the median dose was 6.6 µg/kg.
Overall, 89% of patients treated with romiplostim achieved a platelet response, defined as platelet count ≥50 x 109/L. Tarantino said that patients maintained responses for a median of 11 months and for 75.6% of all months on treatment. When response was calculated from initial response (N = 232), patients maintained the response for a median of 14 months and for 92.3% of treatment months.
Among the 19 patients who had prolonged treatment-free responses, the median duration of the treatment-free intervals was 12 months.
A summary of the safety data showed that 24% of patients had a serious AE during romiplostim treatment, but no fatal AEs occurred. One patient had thrombocytosis associated with a platelet count of 1462 x 109/L at week 14 that persisted for 1 week. Another patient had elevated platelet counts on 10 different occasions during weeks 20 and 172, reaching a maximum of 872 x 109/L but without a thrombotic event.
The most commonly reported AEs in romiplostim-treated patients were headache (40%), epistaxis (39%), pyrexia (32%), and nasopharyngitis. Tarantino reported that 68% of patients had bleeding AEs, most of which were mild or moderate in severity. The most frequent bleeding AEs were epistaxis (39%), contusion (28%), petechiae (24%), and hematoma (15%). The most common serious AE was epistaxis (6%).
Data for 1 patient who had a bone marrow biopsy at investigator request showed an increase in modified Bauermeister bone marrow grade from 0 to 2 without any associated AE. In an ongoing open-label trial, bone marrow biopsies in 32 patients showed no collagen or bone marrow abnormalities.
Tarantino MD, Despotovic J, Roy J, et al. Safety and efficacy of romiplostim in over 200 children with immune thrombocytopenia (ITP): results of an integrated database of 5 clinical trials. In: Proceedings from the 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 2428.