Clinical Epidemiology and Ageing

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

Guillet S, Crickx E, Azzaoui I, Chappert P, Boutin E, Viallard J-F, Rivière E, Gobert D, Galicier L, Malphettes M, Cheze S, Lefrère F, Audia S, Bonnotte B, Lambotte O, Noel N, Fain O, Moulis G, Hamidou M, Gerfaud-Valentin M, Marolleau J-P, Terriou L, Martis N, Morin A-S, Perlat A, Le Gallou T, Roy-Peaud F, Robbins A, Lega J-C, Puyade M, Comont T, Limal N, Languille L, Zarrour A, Luka M, Menager M, Belmondo T, Hue S, Canoui-Poitrine F, Michel M, Godeau B, Mahévas M Blood. 2023;141(23):2867-2877.

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.

MeSH terms: Adult; Autoimmunity; Humans; Hydrazines; Middle Aged; Platelet Count; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin
DOI: 10.1182/blood.2022018665