Durability of Treatment Free Platelet Response in Children with Chronic Immune Thrombocytopenic Purpura Previously Treated with Romiplostim
Authors: Tarantino Michael D , Mistretta Jessica , Ansteatt Kristin T , Kreitzer Sarah , Barclay Dominique 
Published: December 2024

Immune thrombocytopenic purpura (ITP) is the most common acquired platelet disorder in children. ITP in childhood is typically a transient disorder, however, approximately 10% of those diagnosed will experience chronic thrombocytopenia, some for many years. Of children with chronic ITP that require drug treatment, the thrombopoietin receptor agonists (TPO-RAs) have been shown to be effective and safe (Grainger J, et al. Lancet 2015), (Tarantino MD, et al. Lancet 2016). In a long-term extension arm of a prospective pediatric clinical trial of romiplostim, 23% (15 of 65) of children with chronic ITP were weaned completely from romiplostim and achieved a treatment free response (TFR) for more than six months (Tarantino MD, et al. Haematologica 2019). Of the 65 patients, ten were cared for at the Bleeding and Clotting Disorders Institute, their long-term clinical courses after closure of the published trial are described here.
Of the 10 patients, 8 achieved TFR, six during the clinical trial, and two after the trial ended. Seven of the ten were female, with 6 of the 7 females achieving TFR. The median age at ITP diagnosis and duration of ITP at the time of first romiplostim treatment was 5.5 years (1-13 years) and 14 months (5-67 months) in the TFR patients vs. 9.5 years (9, 10 years) and 48 months (23, 73 months) in the non-TFR patients, respectively. Patients who achieved a platelet count &gt; 50 x 109/L in the first four weeks tended to achieve TFR compared to patients who didn't, p = 0.1.
The median time to TFR was 47 months (23-94 months). The median ongoing duration of TFR was 8.1 years (4.7-9.9 years) at the time of this writing. The median number of treatments tried prior to initiation of romiplostim was 3 in both groups, 1-4 in the TFR group and 2, 4 in the non-TFR group, respectively. The median age at time of first romiplostim dose was 8 years (5-15 years) for the TFR group and 13.5 years (13, 14 years) for the non-TFR group, however not statistically significantly different. Two TFR patients that had recurrence of thrombocytopenia achieved TFR after 33 and 94 months of romiplostim treatment, and resumed ITP treatment after 4.5 and 6 months of TFR, respectively. Both regained TFR subsequently, after 15 and 33 months, respectively and continue in TFR at the time of this writing. One of the non-TFR patients was diagnosed with systemic lupus erythematosus 11 years after ITP diagnosis. Otherwise, no new related adverse events during or after romiplostim treatment have been noted.
For these ten pediatric patients with chronic ITP, remission was achieved after nearly 2 to almost 8 years of continuous romiplostim treatment and was sustained (and ongoing) for up to nearly 10 years. In this small subset of pediatric patients with chronic ITP, long-term TFRs associated with romiplostim treatment occurred in the majority without new safety signals. Patient characteristics or drug responses identified in clinical trials (Tarantino, Lancet 2016; Tarantino, Haematologica 2019) as being associated with TFR, younger age at first romiplostim dose and better platelet response in the first four weeks of romiplostim treatment were also suggested in this analysis, however the small number of patients in the non TFR group, perhaps thwarted the differences reaching statistical significance. Certainly, broader surveillance of long-term use of romiplostim in children with ITP will better characterize its safety, efficacy, and the occurrence of TFRs.