Romiplostim and eltrombopag, the two TPO-receptors agonists (TPO-RAs), that have been approved in adult’s ITP show a great clinical efficacy, with a 70 to 80% lasting response-rate in long-term studies. Due to their mechanism of action, the platelet count decreases back to its baseline level within 10 days after TPO-RA withdrawal in the large majority of the cases. However, recent unexpected cases of durable remission after TPO-RAs discontinuation have been reported. The aim of this study was first to look at the proportion of patients in whom TPO-RAs are able to induce a durable response and secondly to describe the characteristics of such patients.
All adults with primary ITP treated by at least one TPO-RA over a 5–year period, seen in one of the 3 participating referral centers, have been included. All patients were consecutively captured through a database, and no one excluded. A complete response (CR) was defined as a platelet count >100 x 109/L, and a response (R) by a platelet count over 30 x 109/L with a least a doubling of the baseline value. Last follow-up was obtained by contacting the physician in care of the patient.
Fifty four patients (35 females) were recruited, including 35 patients (65%) with chronic, 11 (20%) with persistent and 8 (15%) with newly-diagnosed ITP. After a median of 4 treatment-lines (including rituximab in 59% and splenectomy in 33%), 18 received eltrombopag, 22 romiplostim and 14 received both TPO-RAs sequentially for an overall median time of 10 months (range: 1-70 months). The initial overall response rate on TPO-RA was 44/54 (81.5%) with 28/54 patients achieving a CR (51.8%) and 16/54 a R (29.6%). In 20 out of 28 patients achieving a CR, TPO-RA was discontinued. Among them, 6 patients were excluded from the analysis as concomitant or previous treatment at the initiation of TPO-R therapy may have interfered with the response after stopping TPO-RA. Three patients received rituximab either concomitantly (n=2) or 6 months before TPO-RA (n=1); 2 patients were splenectomized either concomitantly (n=1) or 2 months before TPO-RA administration (n=2). In one patient, TPO-RA was stopped while the patient has a newly diagnosed ITP. Among the 14 evaluable patients, 6 (30%) relapsed within 10 days after stopping TPO-RA, requiring a rescue therapy. In 8 patients (70%), a durable CR was observed after TPO-RA discontinuation with a median follow-up period of 13.5 months (range: 5-27 months). All of them had a previous history of chronic ITP (median ITP duration before TPO-RAs: 103 months (13-297)), and have received a median of 5 lines of treatment (2-12). Interestingly, three out of 8 patients received short course (<1 months) of TPO-RA. In this study including a relatively low number of patients, we did not found predictive factor of sustained response (age, gender, duration of ITP, previous number of therapies before TPO-RA).
Our study suggests that almost 15 % of patients treated for chronic ITP with TPO-RA achieve a durable response after treatment discontinuation. A prospective trial is needed to confirm this unexpected rate of response in a larger series of patients and to identify predicting factors of lasting remission.
Off Label Use: Romiplostin, eltrombopag.
Asterisk with author names denotes non-ASH members.
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