Details

Autor(en) / Beteiligte

• Guillet, Stéphanie
• Crickx, Etienne
• Azzaoui, Imane
• Chappert, Pascal
• Boutin, Emmanuelle
• Viallard, Jean-François
• Rivière, Etienne
• Gobert, Delphine
• Galicier, Lionel
• Malphettes, Marion
• Cheze, Stéphane
• Lefrere, François
• Audia, Sylvain
• Bonnotte, Bernard
• Lambotte, Olivier
• Noel, Nicolas
• Fain, Olivier
• Moulis, Guillaume
• Hamidou, Mohamed
• Gerfaud-Valentin, Mathieu
• Marolleau, Jean-Pierre
• Terriou, Louis
• Martis, Nihal
• Morin, Anne-Sophie
• Perlat, Antoinette
• Le Gallou, Thomas
• Roy-Peaud, Frédérique
• Robbins, Ailsa
• Lega, Jean-Christophe
• Puyade, Matthieu
• Comont, Thibault
• Limal, Nicolas
• Languille, Laetitia
• Zarrour, Anissa
• Luka, Marine
• Menager, Mickael
• Belmondo, Thibault
• Hue, Sophie
• Canoui-Poitrine, Florence
• Michel, Marc
• Godeau, Bertrand
• Mahévas, Matthieu

Titel

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

Ist Teil von

• Blood, 2023-06, Vol.141 (23), p.2867-2877

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• •High rate of sustained response after TPO-RA discontinuation in patients with persistent or chronic ITP achieving initial CR on treatment.•Increased expression of CD69 on CD8+ T cells at the time of tapering TPO-RA could predict relapses. [Display omitted] 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. Guillet et al present results of thrombopoietin receptor agonist (TPO-RA) discontinuation in a selected population of patients with persistent or chronic immune thrombocytopenia (ITP). They report that in patients in stable remission with a platelet count of >100 × 109/L for at least 2 months (48 of 388 patients), 56% maintained a platelet count of >30 × 109/L off therapy. This suggests that a subset of patients on chronic treatment with TPO-RA can be successfully tapered off therapy.