Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study

Author(s): 1Stéphanie Guillet;1,2,3Etienne Crickx;1,2Imane Azzaoui;2,4Pascal Chappert;5,6Emmanuelle Boutin;7Etienne Rivière;8Delphine Gobert;9Lionel Galicier;9Marion Malphettes;10Stéphane Cheze;11François Lefrere;12Sylvain Audia;12Bernard Bonnotte;13Olivier Lambotte;13Nicolas Noel;8Olivier Fain;14,15Guillaume Moulis;16Mohamed Hamidou;17Mathieu Gerfaud-Valentin;18Jean-Pierre Marolleau;19Louis Terriou;20Nihal Martis;21Anne-Sophie Morin;22Antoinette Perlat;22Thomas Le Gallou;23Frédérique Roy-Peaud;24Ailsa Robbins;25Jean-Christophe Lega;26Matthieu Puyade;27Thibault Comont;1Nicolas Limal;1Laetitia Languille;1Anissa Zarrour;28Marine Luka;28Mickael Menager;29,30Thibault Belmondo;29,30,31Sophie Hue;5Florence Canoui-Poitrine;1Marc Michel;1Bertrand Godeau;1,2Matthieu Mahévas
Source: Blood (2023) 141 (23): 2867–2877.
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Benign heme article of the month– A significant portion of patients with stable platelet counts can be gently tapered from TPO-agonists. Those who needed to be re-challenged had a good response. This is likely an underutilized strategy.


Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at as #NCT03119974.

Author Affiliations

1Service de Médecine Interne, Centre National de Référence des Cytopénies Auto-Immunes de l’Adulte, Henri Mondor Hôpital, Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Assistance Publique–Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France;2INSERM U1151/CNRS UMS 8253, Institut Necker Enfants Malades, ATIP-Avenir Team AI2B, Université de Paris Cité, Université Paris-Est Créteil (UPEC), Créteil, France;3INSERM UMR U1163,Imagine Institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Université de Paris Cité, Paris, France;4INSERM U955, Équipe 2, Université Paris-Est Créteil (UPEC), Créteil, France;5Unité de Recherche Clinique (Mondor), AP-HP, Henri Mondor Hôpitaux Universitaires, Créteil, France;6INSERM, Institut Mondor de Recherche Biomédicale, Équipe Clinical Epidemiology and Ageing, UPEC, Créteil, France;7Service de Médecine Interne, Haut-Lévêque Hôpital, Université de Bordeaux, Bordeaux, France;8Service de Médecine Interne, Saint Antoine Hôpital, AP-HP, Sorbonne Université, Paris, France;9Service d’Immunologie Clinique, Saint Louis Hôpital, AP-HP, Université de Paris Cité, Paris, France;10Institut d’Hématologie de Basse-Normandie, Centre Hospitalier de Caen Normandie, Caen, France;11Service de Biothérapies, Necker Hôpital, AP-HP, Paris, France;12Service de Médecine Interne et d’Immunologie Clinique, Centre de Référence Constitutif des Cytopénies Auto-Immunes, Hôpital François Mitterrand, Centre Hospitalier Universitaire (CHU) Dijon-Bourgogne, Dijon, France;13Service de Médecine Interne et d’Immunologie Clinique, Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Le Kremlin-Bicêtre, France;14Service de Médecine Interne, CHU de Toulouse, Toulouse, France;15CIC 1436, Équipe PEPSS, CHU de Toulouse, Toulouse, France;16Service de Médecine Interne, CHU de Nantes, Nantes, France;17Service de Médecine Interne, Hôpital la Croix-Rousse, Lyon, France;18Service d’Hématologie Clinique et Thérapie Cellulaire, CHU Amiens-Picardie, Amiens, France;19Service de Médecine Interne et d’Immunologie Clinique, CHU de Lille, Lille, France;20Service de Médecine Interne et d’Immunologie Clinique, Hôpital de Nice, Nice, France;21Service de Médecine Interne, Jean Verdier Hôpital, AP-HP, Bondy, France;22Service de Médecine Interne et Immunologie Clinique, CHU de Rennes, Rennes, France;23Service de Médecine Interne-Maladies Infectieuses et Tropicales, CHU de Poitiers, Poitiers, France;24Department of Internal Medicine, Infectious Diseases, and Clinical Immunology, Robert Debré Hospital, Reims University Hospitals, Reims, France;25Service de Médecine Interne, Hospices Civils de Lyon, Lyon Sud Hôpital, Pierre-Bénite, France;26Service de Médecine Interne, CHU de Poitiers, Poitiers, France;27Service de Médecine Interne, CHU de Toulouse (IUCT-Oncopole), Toulouse, France;28Université Paris Cité, Institut Imagine, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM UMR 1163, F-75015 Paris, France;29Département Immunologie-Hématologie, Henri Mondor Hôpital, AP-HP, UPEC, Créteil, France;30UPEC, Faculté de Médecine, Créteil, France32 Service de Santé Publique, AP-HP, Henri Mondor Hôpitaux Universitaires, Créteil, France;31INSERM U955, Équipe 16, Institut Mondor de Recherche Biomédicale, UPEC, Créteil, France;32Service de Santé Publique, AP-HP, Henri Mondor Hôpitaux Universitaires, Créteil, France

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Introduction to a How I Treat series on management of high-risk patients following allogeneic transplant

Interesting prospective study assessing outcomes in ITP in pregnant women while measuring neonatal ITP in the developing child, with a control of non-pregnant women for comparison. Pregnancy-ITP was associated with a 2.7x higher rate of recurrent disease. However, bleeding was similar in pregnant vs. non-pregnant women. NITP risk was associated with more severe ITP disease in the mother and the severity of the disease, as well as prior h/o ITP in the mother.

Read More »

Efficacy and Safety of Intravenous Efgartigimod in Adults with Primary Immune Thrombocytopenia: Results of a Phase 3, Multicenter, Double-Blinded, Placebo-Controlled, Randomized Clinical Trial (ADVANCE IV)

Another new (potential) option for refractory ITP patients, efgartigimod is an IgG1-Fc-fragment engineered to reduce IgG autoantibody levels.  131 patients enrolled and 67% had >=3 prior lines of therapy, placebo controlled study.  The study group had a 90% sustained platelet response, with >50% having plt counts of >30k >= 7 days apart.

Read More »