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

被引：22

作者：

Guillet, Stephanie ^{[1
]}

Crickx, Etienne ^{[1
,2
,3
]}

Azzaoui, Imane ^{[1
,2
,4
]}

Chappert, Pascal ^{[2
,4
]}

Boutin, Emmanuelle ^{[5
,6
]}

Viallard, Jean-Francois ^{[7
]}

Riviere, Etienne ^{[7
]}

Gobert, Delphine ^{[8
]}

Galicier, Lionel ^{[9
]}

Malphettes, Marion ^{[9
]}

Cheze, Stephane ^{[10
]}

Lefrere, Francois ^{[11
]}

Audia, Sylvain ^{[12
]}

Bonnotte, Bernard ^{[12
]}

Lambotte, Olivier ^{[13
]}

Noel, Nicolas ^{[13
]}

Fain, Olivier ^{[8
]}

Moulis, Guillaume ^{[14
,15
]}

Hamidou, Mohamed ^{[16
]}

Gerfaud-Valentin, Mathieu ^{[17
]}

Marolleau, Jean-Pierre ^{[18
]}

Terriou, Louis ^{[19
]}

Martis, Nihal ^{[20
]}

Morin, Anne-Sophie ^{[21
]}

Perlat, Antoinette ^{[22
]}

Le Gallou, Thomas ^{[22
]}

Roy-Peaud, Frederique ^{[23
]}

Robbins, Ailsa ^{[24
]}

Lega, Jean-Christophe ^{[25
]}

Puyade, Matthieu ^{[26
]}

Comont, Thibault ^{[27
]}

Limal, Nicolas ^{[1
]}

Languille, Laetitia ^{[1
]}

Zarrour, Anissa ^{[1
]}

Luka, Marine ^{[28
]}

Menager, Mickael ^{[28
]}

Belmondo, Thibault ^{[29
,30
,32
]}

Hue, Sophie ^{[29
,30
,31
]}

Canoui-Poitrine, Florence ^{[5
,32
]}

Michel, Marc ^{[1
]}

Godeau, Bertrand ^{[1
]}

Mahevas, Matthieu ^{[1
,2
,4
,33
]}

机构：

[1] Henri Mondor Hop, AP HP, Ctr Natl Reference Cytopenies Autoimmunes Adulte, Serv Med Interne,Federat Hosp Univ TRUE InnovaT Th, Paris, France

[2] Univ Paris Est Creteil UPEC, Univ Paris Cite, Inst Necker Enfants Malad, INSERM U1151,CNRS UMS 8253,ATIP Avenir Team AI2B, Creteil, France

[3] Univ Paris Cite, Imagine Inst, Lab Immunogenet Pediat Autoimmune Dis, INSERM UMR U1163, Paris, France

[4] Univ Paris Est Creteil UPEC, Equipe 2, INSERM U955, Creteil, France

[5] Henri Mondor Hop Univ, AP HP, Unite Rech Clin Mondor, Creteil, France

[6] Inst Mondor Rech Biomed, Equipe Clin Epidemiol & Ageing, INSERM, UPEC, Creteil, France

[7] Univ Bordeaux, Hop Haut Leveque, Serv Med Interne, Bordeaux, France

[8] Sorbonne Univ, St Antoine Hop, AP HP, Serv Med Interne, Paris, France

[9] Univ Paris Cite, St Louis Hop, AP HP, Serv Immunol Clin, Paris, France

[10] Ctr Hosp Caen Normandie, Inst Hematol Basse Normandie, Caen, France

[11] Necker Hop, AP HP, Serv Biotherapies, Paris, France

[12] Ctr Hos Univ CHU Dijon Bourgogne, Hop Francois Mitterrand, Ctr Reference Constitut Cytopenies Autoimmunes, Serv Med Interne & Immunol Clin, Dijon, France

[13] Univ Paris Saclay, Hop Bicetre, AP HP, Serv Med Interne & Immunol Clin, Le Kremlin Bicetre, France

[14] CHU Toulouse, Serv Med Interne, Toulouse, France

[15] CHU Toulouse, Equipe PEPSS, CIC 1436, Toulouse, France

[16] CHU Nantes, Serv Med Interne, Nantes, France

[17] Hop la Croix Rousse, Serv Med Interne, Lyon, France

[18] CHU Amiens Picardie, Serv Hematol Clin & Therapie Cellulaire, Amiens, France

[19] CHU Lille, Serv Med Interne & Immunol Clin, Lille, France

[20] Hop Nice, Serv Med Interne & Immunol Clin, Nice, France

[21] Jean Verdier Hop, AP HP, Serv Med Interne, Bondy, France

[22] CHU Rennes, Serv Med Interne & Immunol Clin, Rennes, France

[23] CHU Poitiers, Serv Med Interne Malad Infect & Trop, Poitiers, France

[24] Reims Univ Hosp, Robert Debre Hosp, Dept Internal Med Infect Dis & Clin Immunol, Reims, France

[25] Hosp Civils Lyon, Lyon Sud Hop, Serv Med Interne, Pierre Benite, France

[26] CHU Poitiers, Serv Med Interne, Poitiers, France

[27] CHU Toulouse IUCT Oncopole, Serv Med Interne, Toulouse, France

[28] Univ Paris Cite, Inst Imagine, Lab Inflammatory Responses & Transcript Networks D, Atip Avenir Team,INSERM UMR 1163, F-75015 Paris, France

[29] Henri Mondor Hop, AP HP, Dept Immunol Hematol, UPEC, Creteil, France

[30] UPEC, Fac Med, Creteil, France

[31] UPEC, Inst Mondor Rech Biomed, Equipe 16, INSERM U955, Creteil, France

[32] Henri Mondor Hop Univ, AP HP, Serv Sante Publ, Creteil, France

[33] Henri Mondor Univ Hosp, AP HP, Dept Internal Med, 51 Ave Marechal de Lattre de Tassigny, F-94000 Creteil, France

来源：

BLOOD | 2023年 / 141卷 / 23期

关键词：

CHRONIC IMMUNE THROMBOCYTOPENIA; T-CELLS; TERM TREATMENT; DOUBLE-BLIND; PURPURA; THROMBOPOIETIN; ELTROMBOPAG; REMISSION; ROMIPLOSTIM; ACTIVATION;

D O I：

10.1182/blood.2022018665

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 10(9)/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 x 10(9)/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 alpha signaling via NF-kappa B 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.

引用

页码：2867 / 2877

页数：11

共 41 条

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