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583 Rate of Prolonged Response after Stopping Thrombopoietin-Receptor Agonists Treatment in Primary Immune Thrombocytopenia (ITP): Results from a Nationwide Prospective Multicenter Interventional Study (STOPAGO)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Thrombopoietin Receptor Agonists and Other Clinical Topics in Thrombocytopenia
Hematology Disease Topics & Pathways:
Clinical Trials, Clinical Research
Monday, December 13, 2021: 10:30 AM

Matthieu Mahevas1,2*, Stephanie Guillet3*, Jean-Francois Viallard, M.D, PhD4*, Delphine Gobert, M.D5*, Marion Malphettes, MD6*, Stephane Cheze, MD7*, Francois Lefrere, MD8*, Sylvain Audia, M.D, PhD9*, Bernard Bonnotte, MD, PhD10*, Olivier Lambotte11*, Nicolas Noel12*, Olivier Fain, MD13*, Guillaume Moulis, MD14*, Mohamed Hamidou, M.D15*, Mathieu Gerfaud-Valentin, MD16*, Jean Pierre Marolleau17, Louis Terriou, MD18*, Nihal Martis19*, Anne-Sophie Morin20*, Antoinette Perlat, M.D21*, Thomas le Gallou22*, Frédérique Roy-Peaud23*, Ailsa Robbins24*, Nicolas Limal25*, Laetitia Languille26*, Anissa Zarour27*, Emmanuelle Boutin, MD28*, Florence canouï-Poitrine29*, Marc Michel, MD30* and Bertrand Godeau, MD31*

1IMRB U955 INSERM, équipe 2, Université Paris Est Créteil (UPEC), Créteil, France
2Service de Médecine Interne, Centre national de référence des cytopénies auto-immunes de l’adulte, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Creteil, France
3Department of Internal Medecine, Henri Mondor University Hospital, Creteil, France
4Haut-Leveque Hospital, Pessac, FRA
5Internal Medicine, Saint-Antoine Hospital, Paris, France
6Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris, PARIS, FRA
7Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire de Caen Normandie, Caen, France
8Biotherapy Department, Necker: Assistance Publique-Hôpitaux de Paris, PARIS, FRA
9CHU de Dijon, Dijon, France
10Faculty of Medicine - University Hospital of Dijon, Dijon, FRA
11CHU Bicêtre, Le Kremlin Bicetre, FRA
12APHP, Le Kremlin-Bicetre, France
13Internal Medicine, Saint Antoine University Hospital, université Paris-Sorbonne, Paris, France
14CHU de Toulouse, Toulouse, France
15CHU NANTES, NANTES, FRA
16Department of Internal Medicine, Hôpital Croix Rousse, Lyon, France
17Hopital SUD, Amiens, Cedex 1, France
18Service de Médecine Interne et Immunologie Clinique, Centre Hospitalier Universitaire de Lille, Lille, France
19CHU De Nice, Nice, FRA
20Department of Internal Medicine, Bondy Hospital, Bondy, FRA
21CHU Rennes, Rennes, FRA
22Hopital Pontchaillou-CHU Rennes, Rennes, France
23CHU De Poitiers, Poitiers, FRA
24Reims University Hospital Center, Reims, FRA
25Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, FRA
26Henri Mondor University Hospital, Créteil, France
27Henri Mondor University Hospital, Creteil, France
28Department of Public Health and Biostatistics, Henri Mondor Hospital, Créteil, France
29Department of Public Health and Biostatistics, Henri Mondor Hospital, Creteil, France
30Henri Mondor University Hospital, Université Paris-Est Créteil, Creteil, France
311 Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France

Background: Thrombopoietin receptor agonists(TPO-RAs) have been thought to play only a supporting role in ITP management. Several retrospective studies and a recent prospective study have reported unexpected cases of durable remission after TPO-RAs discontinuation in adult ITP in up to 30%. However, newly diagnosed ITP cases for which spontaneous remission may occur have been included in most of these studies. Thus, the main purpose of this study was to determine the proportion of patients with either persistent or chronic phase and no recent exposure to any potentially curative therapy (i.e., splenectomy or rituximab) achieving long-term remission off-treatment at 24 and 52 months after at least 3 months of TPO-RAs exposure with a complete response (CR).

Patients/methods: We conducted a nationwide prospective multicenter interventional study (NCT03119974). Inclusion criteria were: 1) Patients aged > 18 years, with persistent or chronic primary ITP, 2) A stable CR defined by a platelet count > 100 x 109/L for more than 2 months on TPO-RA therapy, 3) Treatment with TPO-RA for at least 3 months. Main exclusion criteria were: 1) Anticoagulation or anti-platelet treatment, 2) Previous failure of TPO-RA discontinuation, 3) Concomitant treatment with corticosteroids ± intravenous immunoglobulin 4) Rituximab or splenectomy within the 2 months preceding or after TPO-RA initiation. After inclusion, the decrease and wean of either eltrombopag or romiplostim was initiated according to a standardized protocol (respectively tapering of 25 mg every 2 weeks or tapering of 1 ug/kg every week). In any case TPO-RAs had to be stopped at week 10. In case of relapse after TPO-RA discontinuation, the decision to start a new therapy was left at every investigator discretion. The primary endpoint was the proportion of patients achieving an overall response (CR + R) at week 24 (6 months) after TPO-RAs discontinuation. Secondary outcomes were overall response rate over the study period (W52), bleeding events, and to identify predictive factors, for overall prolonged response (W24 and W52).

Results: Forty-nine patients (30 females, 61%), with persistent (n=2) or chronic (n=47, 96%) chronic ITP, with a median age of 58.5 years IQR (41 to 73) fulfilling the eligibility criteria were included over 2 year-period in 22 centers from the French reference network for adult’ ITP. Forty patients received eltrombopag and 9 romiplostim at the time of inclusion. One patient was excluded since she was diagnosed pregnant one day after inclusion. In intention to treat 27/48 (56.2%; 95% CI, 29.5 to 58.8) patients achieved the primary-endpoint and maintained an overall response at week 24 after TPO-RAS discontinuation with a complete response for 15/27 (55%). During the full follow-up period of 52 weeks after TPO-RAs discontinuation, overall response was observed in 25/48 (52.1%; 95% CI, 37.2 to 66.2) patients (Figure 1). Bleeding events occurred in 13/21 (61.9%) and 15/23 (65.2%) patients relapsing respectively at 24 and 52 months with a median platelet count of 31´109/L(26 to 39) and 31 ´109/L(23 to 39). No severe bleeding episode (French bleeding score > 8) occurred. Median time of relapse after tapering initiation was 8 weeks. Among 21 patients with a relapse (<30 x 109/L) before week 24, 13 patients were re-challenged with the same TPO-RA with a CR achieved with a median time of 2 weeks (2-4). In univariate analysis, age, ITP duration, TPO-RA duration before discontinuation, platelet count at inclusion and TPO-RAs drug class were not predictive of sustained response.

Conclusion: These results showed an unexpectedly high rate of sustained off-treatment remission after TPO-RAs discontinuation in chronic ITP among patients who initially achieve a stable CR. When they occur, relapses are mainly observed within the first weeks after discontinuation, very rarely afterwards and with no severe bleeding. While no predictive factor of lasting remission has been yet identified, our study strongly supports a progressive tapering of the dose of TPO-RAs in patients achieving a stable CR on treatment.

Figure 1: Relapse at 52 weeks after TPO-RAs discontinuation

Disclosures: Mahevas: GSK: Research Funding; Amgen: Honoraria. Viallard: Novartis: Consultancy; Grifols: Consultancy; LFB: Consultancy; Amgen: Consultancy. Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenx: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Michel: Novartis: Consultancy; Amgen: Consultancy; UCB: Honoraria; Argenx: Honoraria; Rigel: Honoraria; Alexion: Honoraria. Godeau: Sobi: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Grifols: Consultancy.

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