Long-term treatment with romiplostim and treatment-free platelet responses in children with chronic immune thrombocytopenia

Abstract

Children with immune thrombocytopenia for ≥6 months completing a romiplostim study received weekly subcutaneous romiplostim (1-10 μg/kg targeting platelet counts of 50-200×109/L) in this extension to examine romiplostim’s long-term safety and efficacy. Sixty-five children received romiplostim for a median of 2.6 years (range: 0.1-7.0 years). Median baseline age was 11 years (range: 3-18 years) and platelet count was 28×109/L (range: 2-458×109/L). No patient discontinued treatment for an adverse event. Median average weekly dose was 4.8 mg/kg (range: 0.1-10 mg/kg); median platelet counts remained >50×109/L, starting at week 2. Nearly all patients (94%) had ≥1 platelet response (≥50×109/L, no rescue medication in the previous 4 weeks), 72% had responded at ≥75% of visits, and 58% had responded at ≥90% of visits. Treatment-free response (platelets ≥50×109/L ≥24 weeks without immune thrombocytopenia treatment) was seen in 15 of 65 patients while withholding romiplostim doses. At onset of treatment-free response, the nine girls and six boys had a median immune thrombocytopenia duration of four years (range: 1-12 years) and had received romiplostim for two years (range: 1-6 years). At last observation, treatment-free responses lasted for a median of one year (range: 0.4-2.1 years), with 14 of 15 patients still in treatment-free response. Younger age at first dose and platelet count >200×109/L in the first four weeks were associated with treatment-free responses. In this 7-year open-label extension, three-quarters of the patients responded ≥75% of the time, and romiplostim was well tolerated, with no substantial treatment-related adverse events. Importantly, 23% of children maintained treatment-free platelet responses while withholding romiplostim and all other immune thrombocytopenia medications for ≥6 months. (Registered at clinicaltrials.gov identifier: 01071954)

The role of romiplostim for pediatric patients with immune thrombocytopenia

“…25 In the phase III study, 83% of romiplostim-treated patients had bleeding events, but nearly all were mild epistaxis, petechiae, contusion, or gingival bleeding; there were no intracranial hemorrhages or fatal bleeding. 33 Similar findings were seen in the extension study following the phase III trial 34 and have been reported from a large international prospective open-label study published in abstract form. 37 Potential adverse events of greatest concern with the long-term use of romiplostim are thromboembolic events and bone marrow fibrosis.…”

Romiplostim treatment for children with immune thrombocytopenia: Results of an integrated database of five clinical trials

“…This pooled analysis combined data from pediatric patients across five clinical trials of romiplostim: two completed double‐blind, placebo‐controlled trials, two completed open‐label extensions, and one ongoing open‐label trial (Figure 1A). Detailed study methods have been published for each of the completed double‐blind placebo‐controlled trials 8,9 and open‐label extensions 10,11 . A meeting abstract summarized the study methods for the ongoing open‐label 3‐year single‐arm trial 12 .…”

“…The first open‐label extension (NCT00116688) enrolled patients (n = 20) who completed the phase 1/2 double‐blind clinical trial, regardless of their age at study entry 10 . The second open‐label extension (NCT01071954) enrolled patients (n = 66) who either rolled over from the first extension (n = 12) or completed the phase 3 double‐blind clinical trial (n = 54); to enter the second extension, patients were required to be 17 years of age upon study entry 11 . Patients in each extension received open‐label romiplostim: for up to 109 weeks in the first extension, and for up to 7 years in the second extension 10,11 …”

“…More comprehensive and longitudinal data are needed on the use of romiplostim in children with ITP. Five romiplostim clinical trials conducted over more than 15 years (from 2004 to the present), including four completed trials and one ongoing trial, have examined the use of romiplostim in children with ITP 8‐12 . The objective of this integrated analysis was to examine the safety and efficacy of romiplostim in children with ITP across these clinical trials.…”

Immunomodulation in Primary Immune Thrombocytopenia: A Possible Role of the Fc Fragment of Romiplostim?

“…Recently a romiplostim extension study in children with chronic ITP demonstrated treatment-free responses (platelet count ≥50 × 10 9 /L) in 23% of patients withholding all platelet-enhancing drugs. Younger age at first dose and a platelet count >200 × 10 9 /L in the first 4 weeks of treatment were associated with sustained response lasting ≥6 months (20).…”