Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry

• Type of Material: Article
• Authors: Charles Bowers, Amgen Inc; Daniel T Mytych, Amgen Inc; Tatiana Lawrence, Amgen Inc; Kejia Wang, Amgen Inc; Troy E Barger, Amgen Inc; Melissa Eisen, Amgen Inc; Carolyn Bennett, Emory University; Michael D Tarantino, University of Illinois College of Medicine-Peoria
• Language: English
• Date: 2021-12-03
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by The American Society of Hematology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2021005105
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 5
• Issue: 23
• Start Page: 4969
• End Page: 4979
• Keywords: Life Sciences & Biomedicine; CHILDREN; IMMUNE THROMBOCYTOPENIA; INTRAVENOUS IMMUNOGLOBULIN; Hematology; RECOMMENDATIONS; Science & Technology; HOST ANTIBODIES; THROMBOPOIETIN; MANAGEMENT; DOUBLE-BLIND
• Research Categories: Health Sciences, Oncology

Abstract

Development of first-generation thrombopoietins (TPOs) was halted due to antibodies that neutralized endogenous TPO, causing protracted thrombocytopenia in some patients. The second-generation TPO receptor agonist romiplostim, having no homology to TPO, was developed to circumvent potential immunogenicity. We examined the development of binding and neutralizing antibodies to romiplostim and TPO among pediatric patients with primary immune thrombocytopenia (ITP) in 5 clinical trials and a global postmarketing registry. In the trials, 25 of 280 (8.9%) patients developed anti-romiplostim binding antibodies. The first positive result was detected 67 weeks (median) after romiplostim treatment was initiated. The median romiplostim dose was 8 mg/kg, and the median platelet count was 87 3 109/L. Most patients who developed anti-romiplostim binding antibodies (18 of 25 [72%]) had $90% of platelet assessments showing a response. Anti-romiplostim neutralizing antibodies developed in 8 of 280 (2.9%) patients. The development of anti-romiplostim neutralizing antibodies was unrelated to the romiplostim dose, and most patients who developed the antibodies (7 of 8 [88%]) had platelet response. Nine of 279 (3.2%) patients developed anti-TPO binding antibodies, and 1 (0.4%) developed transient anti-TPO neutralizing antibodies. In 8 patients who developed anti-romiplostim neutralizing antibodies, no TPO cross-reactivity was observed. In the postmarketing registry, 3 of 19 (15.8%) patients developed anti-romiplostim binding antibodies; 1 (5.3%) patient developed anti-romiplostim neutralizing antibodies. These results suggest that immunogenicity to romiplostim occurs infrequently in pediatric patients with ITP and is generally not associated with loss of platelet response or other negative clinical sequelae.