PF689 SAFETY AND EFFICACY OF ROMIPLOSTIM IN OVER 200 CHILDREN WITH PERSISTENT OR CHRONIC IMMUNE THROMBOCYTOPENIA (ITP) IN AN INTEGRATED DATABASE OF 5 CLINICAL TRIALS

Background: Romiplostim is approved for use in patients 1 year of age or older with ITP for ≥6 months (USA) or chronic ITP (EU) who are refractory to other treatments. Comprehensive data are needed for romiplostim use in children with persistent ITP (6–12 months) or chronic ITP (>1 year). Aims: To examine romiplostim safety and efficacy across trials in children with ITP. Methods: Data were combined from a placebo‐controlled phase 1/2 trial (n = 22; Bussel Blood 2011), a placebo‐controlled phase 3 trial (n = 62; Tarantino Lancet 2016), a 3‐year phase 3 trial (n = 204; Grainger ASH 2017), and 2 extension trials (Bussel PBC 2015; Tarantino ASH 2017). Controlled trials and 3‐year trial enrolled children <18 years with ITP for ≥6 months and ≥1 prior ITP therapy. Extension trials enrolled patients from controlled trials. Romiplostim was titrated (1–10 μg/kg/week in most trials) to maintain platelet count 50–200x10 9 /L. Results: The 286 treated patients (initially placebo, 24; romiplostim, 262) had a median age of 10 years, ITP duration of 1.9 years, and baseline platelet count of 14x10 9 /L. Of 282 patients exposed to any romiplostim, including 20 after placebo, 69 (24%) had ITP for 6–12 months (persistent ITP) and 213 (76%) had ITP for >1 year (chronic ITP) at baseline. Median duration of romiplostim treatment was 65 weeks (persistent ITP, 65 weeks; chronic ITP, 66 weeks), including >48 weeks for 62% of patients, and median dose was 6.6 μg/kg/week. After starting romiplostim, 24% (persistent ITP, 17%; chronic ITP, 27%) had a serious adverse event (AE), most commonly epistaxis (6%). Bleeding AEs were reported for 68% of patients (persistent ITP, 65%; chronic ITP, 69%), including 10% with grade ≥3 bleeding and 2 patients with grade ≥4 bleeding. Seven patients had postbaseline neutralizing antibodies against romiplostim (2 transient). No patient had neutralizing antibodies against endogenous thrombopoietin. One patient had an increase in modified Bauermeister bone marrow grade from 0 to 2 (fine reticulin fiber network) with no associated AE, platelet count ≥30x10 9 /L, and no follow‐up biopsy. Among patients with bone marrow biopsy in the ongoing 3‐year trial (Year 1, n = 27; Year 2, n = 5), there were no findings of collagen or bone marrow abnormalities vs baseline. Overall, 89% of romiplostim‐treated patients (persistent ITP, 88%; chronic ITP, 90%) and 8% receiving placebo had a platelet response (≥50x10 9 /L). Median time to platelet response for romiplostim was 6 weeks (persistent ITP, 5 weeks; chronic ITP, 6 weeks). Median platelet counts remained between 50 and 200x10 9 /L with weekly romiplostim treatment and dose titration. Median time per month with platelet response was 76% overall (persistent ITP, 81%; chronic ITP, 74%) and 92% after first response (persistent ITP, 92%; chronic ITP, 93%). Nineteen patients (persistent ITP, 7; chronic ITP, 12) maintained platelet counts ≥50x10 9 /L while withholding all ITP therapies for ≥6 months (treatment‐free response); all had received romiplostim before treatment‐free response. Median duration of treatment‐free responses was 12 months (persistent ITP, 12 months; chronic ITP, 11 months). Summary/Conclusion: In this comprehensive database of romiplostim ITP trials with 468 patient‐years of romiplostim exposure, romiplostim was well tolerated, and no immunogenicity or bone marrow issues were identified. Most patients had a platelet response to romiplostim; some achieved a treatment‐free response while withholding all ITP therapies. Median treatment duration, tolerability, and platelet responses were similar between children with persistent or chronic ITP at baseline.