Real World Romiplostim Dosing and Response in Pediatric Immune Thrombocytopenia

Introduction: Romiplostim, a thrombopoietin receptor agonist (TPO-RA), is an approved treatment for pediatric immune thrombocytopenia (ITP). Guidelines recommend treatment with TPO-RAs in children with mucosal bleeding and/or impaired quality of life who fail first line therapy. The FDA approved prescribing information recommends an initial weekly subcutaneous dose of 1 mcg/kg. Many patients are initiated on higher doses of romiplostim with a goal of minimizing bleeding and time to platelet response. A prior study reported increased thrombosis in adults with ITP who received initial romiplostim doses >5 mcg/kg (King et al, 2023). The objective of this study is to describe starting doses, response rates, and incidence of thrombosis in pediatric patients with ITP treated with romiplostim.

Methods: This single center observational cohort study included 58 pediatric patients with a diagnosis of ITP treated with romiplostim. Collected clinical data included initial and maximum romiplostim dosing by weight, platelet counts, bleeding scores (Modified Buchanan & Adix score), and thrombotic events. Romiplostim response was defined as platelet count > 50 x 10⁹/L on at least one measurement in the absence of rescue therapy. Outcomes were summarized using descriptive statistics. Statistical analysis was performed using Graphpad. Fischer's exact tests were performed for categorical data and Mann-Whitney tests were performed for continuous variables.

Results: The median age was 12.3 years (range: 10 months-21.9 years) with 31% (n=18) with newly diagnosed ITP, 38% (n=22) with persistent ITP and 29% (n=17) with chronic ITP, and 2% (n=1) with unknown ITP phase at time of romiplostim initiation. Patients had received a median of 3 (range: 1-6) ITP directed therapies before romiplostim initiation. Highest bleeding score prior to romiplostim initiation was grade 1 (1.7%, n=1), grade 2 (6.9%, n=4), grade 3 low risk (13.8%, n=8), grade 3 high risk (55.2%, n=32), grade 4 (13.8%, n=8), grade 5 (3.4%, n=2), unknown (1.7%, n=1). Overall romiplostim response rate was 83% (48/58). Platelet response to the initial romiplostim dose was achieved in 38% (22/54) of patients. Patients with initial romiplostim dose ≥ 3 mcg/kg had higher likelihood of romiplostim response on their initial dose than those with initial dose < 3 mcg/kg (initial response rate 52% versus 15%, p=0.0171). Romiplostim dose increase was required in 80% (45/56 patients). Among those with an initial romiplostim dose < 3 mcg/kg, 95% required a dose increase. Patients with a response to the initial dose were started on a significantly higher initial dose than those who did not respond (median 4.0 mcg/kg in initial responders vs 3.0 mcg/kg in initial non-responders, p=0.0048). Patients who required dose increases had significantly lower initial romiplostim doses (median 3 mcg/kg vs 5 mcg/kg, p=0.0007). Initial romiplostim dose was ≥ 5 mcg/kg in 21% of patients.

Although initial dose impacted likelihood of initial response, initial romiplostim dose was not significantly different between overall responders and non-responders (median initial dose 3.6 mcg/kg in responders vs 3.1 mcg/kg in non-responders, p=0.9951). There was no difference in overall response rate by ITP phase at time of romiplostim initiation (p=0.4313) or between those with primary versus secondary ITP (p=0.2444). Among patients who previously failed eltrombopag, 67% (10/15) had an overall response to romiplostim. Overall, 3.4% (n=2) had thrombosis; one patient with an immunodeficiency s/p stem cell transplant with comorbid autoimmune enteropathy, lymphoproliferation, and GI GVHD had portal vein thrombus 4 months after discontinuing romiplostim, and one patient had portal vein thrombus diagnosed three days after emergent splenectomy.

Conclusions: In this pediatric ITP cohort with significant bleeding, initial romiplostim dose ≥ 3 mcg/kg is associated with higher likelihood of initial romiplostim response. Thrombosis after romiplostim is rare in the pediatric population. Both cases of thrombosis in this cohort were attributable to other secondary causes. Initial romiplostim doses ≥ 3 mcg/kg appear to be safe and correlate with a higher likelihood of initial response in children with ITP.

Grace:Agios, Sobi, Novartis: Research Funding; Agios, Sanofi, Sobi: Consultancy.