Sustained Responses following Treatment with Romiplostim in Immune Thrombocytopenia: A Single-Centre Experience

Abstract

Background: Thrombopoietin-receptor agonists (Tpo-RAs) are highly effective in immune thrombocytopenia (ITP). In the last years, cases of durable remission after Tpo-RA discontinuation in adults' ITP have been reported. This observation raises the possibility that these agents may restore immune tolerance to Tpo- RAs in some patients and supports the practice of down titrating the dose. In this moment, there are no studies that show association with the remission and the variables studied. Aims: Our objective is to remark the results about the remission and the discontinuation to thrombopoietin-receptor agonists in our population. Methods: We analyzed 28 patients in treatment with romiplostin from Dr. Negrin Hospital from 2009 to nowadays. Five of them were Primary ITP and 3 had a Secondary ITP (SLE, Crohn's Disease, and hypothyroidism). The average of previously received treatments before the use of romiplostin was either 1 or 2. 8 out of 28 patients, maintained the platelet response in spite of having discontinued therapy with Romiplostim. The discontinued therapy was performed in different ways: 1 patient's drug was decreased weekly to 1 μg/kg and then stopped. In another patient we maintained the dose but increased the interval between treatments to every 3 weeks until off treatment, and as to the remaining 6 patients, the minimal dose was performed every 2-3 weeks until suspension. All of them have maintained the platelet count without therapy. Results: The median dose of romiplostim was 2 μg/kg weekly (range 1-10 μg/kg). The median duration of romiplostim treatment was 21 months (range 8-46 months). 8 patients (28%) responded (platelet count >100x109 /L without concomitant ITP therapy). In seven patients (26.3%) remission was sustained for longer than 6 months after discontinuing romiplostim therapy. Characteristics of these patients are outlined in Table 2. Summary/Conclusions: There is more than one possible mechanism which might explain the lasting responses seen in our patients. For example, natural remission or a change in immune regulation through an impact on T regulatory cells with restoration of immune tolerance. In our retrospective study, and in the other reported studies, we found no relationship between the different variables (age and number of previous lines) or the response pattern (early or late) and the possibility of discontinuance. In addition, we observed that the use of demand doses does not predict the loss of long-term response. The thrombopoietin receptor agonists could be used for short term treatment to cover invasive procedures and to treat patients who are at risk of bleeding and are refractory to other therapies but prospective studies should be set up to confirm the observation of sustained response off therapy and to identify potential predictive factors of response. (Table Presented).