A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia
This is a promising new agent for ITP, where the median time of 50K platelets is one week. This is a small study though, awaiting more data in the future.
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.
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.
ABSTRACT
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 www.clinicaltrials.gov 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, FranceRelated Articles
Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS)
This great Italian study uses eltrombopag in patients with low/intermediate risk MDS. The intervention arm had significantly fewer minor bleeding events and better platelet counts that were durable. Those with higher baseline Hb’s seemed to respond better to therapy, particularly if the Hb was >8g/dL. AML evolution/blast progression was not more common in the treatment arm, which refutes some prior concerns.
The role of CD8+ T-cell clones in immune thrombocytopenia
Thought provoking article regarding a non-antibody mediated mechanism in chronic ITP.
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.
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.
