PF695 ELTROMBOPAG AS SECOND LINE THERAPY IN ADULT PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) IN ATTEMPT TO TREATMENT‐FREE REMISSION. UPDATED RESULTS OF A PHASE II PROSPECTIVE STUDY BY GIMEMA GROUP
Authors: E. Lucchini, F. Palandri, S. Volpetti, N. Vianelli, G. Auteri, E. Rossi, A. Patriarca, G. Carli, W. Barcellini, F. Rotondo, U. Consoli, F. Valeri, C. Santoro, E. Crea, M. Vignetti, E. Boggio, U. Dianzani, I. Giardini, M. Carpenedo, F. Rodeghiero, R. Fanin, F. Zaja
Journal: HemaSphere (2019)

Background: Considering their mode of action, it is expected that the efficacy of thrombopoietin receptor‐agonists (TPO‐RAs), eltrombopag (ELT) and romiplostim, depends on their continuous administration. However, durable remissions after their discontinuation have been described in 10–30% of ITP patients (pts), suggesting a possible immunomodulatory activity. Aims: The aim of this prospective study is to explore the role of ELT given for a defined period of time as second‐line treatment in pts with newly diagnosed (ND) or persistent (P) ITP, aiming to interfere with the pathogenesis of the disease at an early stage, when the immune system dysregulation is milder and reversible. Methods: Pts aged ≥18 years with ND or P ITP not responsive or in relapse after standard first‐line therapy, with active disease (platelet count &lt;30x10 9 /L or steroids/IVIG dependence to maintain a platelet count ≥30x10 9 /L and/or avoid bleeding) were included. The study was divided into a period of treatment (PT) (24 weeks), during which pts received ELT at a starting dose of 50 mg/day, then adjusted according to platelet count; a period of tapering and discontinuation (PTD) (week 25–32), and a period of observation (PO) (week 33–52). Complete response (CR), response (R) and no response were defined according to IWG standard criteria. Only pts in R or CR at the end of week 24 entered the PTD. The primary end‐point was the treatment‐free remission (TFR) i.e. the proportion of pts who, being in remission at the end of PT, was able to taper down and discontinue ELT, maintaining the remission during the PO, without other therapies. Secondary objectives included the relationship between baseline TPO serum level (measured using an ELISA‐based assay) and response to treatment and exploring modifications of immunological parameters and their correlation with responses. The Mann Whitney Wilcoxon test was used to determine statistical significance (defined by p &lt; 0.05). Results: Between 24/02/16 and 05/05/2018, 55 pts were enrolled by 10 GIMEMA Italian Centers. 3 pts didn’t meet the inclusion criteria and 1 was excluded because of protocol violation. Of the 51 evaluable pts, 61% were females. Median age was 65 years (range 21–90). 22 (43%) had ND ITP. Median baseline platelet count was 19x10 9 /L. Median baseline TPO levels, evaluable in 44/51 (86%) of pts, was 47.6 pg/mL (range 31.3–607.7). The overall response rate (ORR) at week 24 was 67% (33% CR). All the 34 responders completed the PTD: 17 (50%) maintained the response (21% CR), while 50% relapsed. At the time of data cut‐off, 6/34 pts have not completed yet the PO. 28/34 pts were evaluable at the end of PO: TFR was observed in 8/28 responders (29%) and in 8/45 evaluable pts (18%). 20 pts relapsed: 17 during the PTD and 3 during the PO. Pts with higher baseline TPO levels had a trend to higher probability to achieve a CR at week 4 (p = 0.06) but not the TFR. 23 pts (45%) reported a total of 65 adverse events (AEs), including 15 serious adverse events. Summary/Conclusion: These preliminary data showed that after 6 months of therapy, the ORR to ELT in pts with ND or P ITP is 67% (33% CR). Among pts who started the tapering, the ones that don’t relapse within the PTD (week 32) are more likely to achieve longer TFR. For pts who don’t maintain the response, ELT can be a steroid‐sparing agent used as a bridge to the chronic phase or other treatments. Differently from what expected, TPO serum levels are not adequately increased in ITP pts. Baseline TPO level doesn’t seem to predict TFR. This analysis is too early to define a correlation between the response and immunological parameters. image