Final safety and efficacy data of long-term open-label dosing of subcutaneous (SC) romiplostim in children with immune thrombocytopenia (ITP)

Abstract

Background: Children with ITP for ≥6 months who completed a romiplostim phase 1/2 or 3 study could enter an open-label extension. Aims: Final extension data for these children with ITP treated with romiplostim are described here. Methods: All patients received weekly SC romiplostim, adjusted weekly by 1 μg/kg/week from 1-10 μg/kg to target platelet counts of 50-200×109/L. Incidence of adverse events (AEs) was the primary endpoint. Results:Median (min-max) treatment for the 65 patients was 135 (5-363) weeks for a total of 182 patient-years, or 2.8 years / patient. Baseline median (min-max) age was 11 (3-18) years; 56% were female; 9.1% had prior splenectomy. Median (min-max) average weekly dose was 4.8 (0.1-10.0) μg/kg, including dose escalation; 20 patients started on 1 g/kg. All 65 patients received their doses per protocol >90% of the time; 21 missed ≥1 dose for noncompliance for a total of 65 times. Reasons for discontinuing romiplostim (n=28, 42%) included consent withdrawn (n=10), other therapy (n=6), and AE (n=2) (asthenia, headache, dehydration, and vomiting in one patient and anxiety in the other; per investigators, none were treatment related). Fifty-four serious AEs occurred in 19 patients but were treatment related in only one patient (concurrent grade 4 thrombocytopenia, grade 3 epistaxis, and grade 2 anemia). Bleeding AEs occurred in 57 patients; 3 were deemed treatment related (injection site hemorrhage, injection site bruising, and epistaxis). No thrombotic events were reported. Bone marrow biopsies were performed for 2 patients with additional cytopenias; both had irondeficiency anemia. Upon leaving the study to receive other therapy, one patient had anti-romiplostim neutralizing antibody (Ab) which was absent on retesting 3 and 6 months later. No patients had anti-TPO neutralizing Ab.Median platelet counts were >50×109/L from week 2 on and >100×109/L from weeks 24-260 (Figure 1).Nearly all (94%, 61/65) patients had ≥1 platelet response (platelet counts ≥50×109/L, excluding counts ≤4 weeks after rescue medication). Most (72%, 47/65) patients had a platelet response ≥75% of the time and 58% (38/65) did ≥90% of the time. Sixty (92%) patients (or caregivers) self-administered romiplostim. Twenty-three (35%) patients received rescue medications; usage was highest in the first few months. Fifteen (23%) patients had treatment-free periods of platelet counts ≥50×109/L for ≥24 weeks (here also called remission; Table 1, Figure 1); these patients (9 girls, 6 boys) had had ITP for a median (min-max) of 3.5 (1.3-13) years, none had prior splenectomy, and had received romiplostim for 2.1 (0.7-6) years. All 15 of these patients had platelet counts over 100×109/L for ≥3 months and 12/15 for ≥6 months. The median (min-max) duration of being ≥100×109/L for these 15 patients was 42 (13-109) weeks. Of baseline characteristics such as sex, platelet counts, ITP duration, and number of past ITP treatments (1, 2, 3, >3), only age <6 years was predictive of developing treatment-free periods ≥24 weeks (p=0.0035). Summary and Conclusions: Seven years of data from this open-label extension study of romiplostim in children with ITP show that >90% of children achieved a platelet response with romiplostim. Romiplostim was mostly well tolerated. Importantly, 23% of these patients with longstanding ITP (median 3.5 years) were able to discontinue all ITP medications (including romiplostim) for at least 6 months.L6259220902019-01-18 <br />