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

Date publication

mars 2023

Journal

Blood

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BONNOTTE Bernard

Tous les auteurs :
Guillet S, Crickx E, Azzaoui I, Chappert P, Boutin E, Viallard JF, Riviere E, Gobert D, Galicier L, Malphettes M, Cheze S, Lefrere F, Audia S, Bonnotte B, Lambotte O, Noel N, Fain O, Moulis G, Hamidou M, Gerfaud-Valentin M, Marolleau JP, Terriou L, Martis N, Morin AS, Perlat A, Le Gallou T, Roy-Peaud F, Robbins A, Lega JC, Puyade M, Comont T, Limal N, Languille L, Zarour A, Luka M, Ménager MM, Belmondo T, Hue S, Canoui-Poitrine F, Michel M, Godeau B, Mahevas M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36893453

Résumé

Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/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 median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα 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 of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974.

Référence

Blood. 2023 03 9;: