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Platelet Biology & its Disorders
Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial
Matthieu Mahévas,1,2,3 Imane Azzaoui,1,3* Etienne Crickx,1,2,3*
Florence Canoui-Poitrine,4 Delphine Gobert,5 Laetitia Languille,1 Nicolas Limal,1 Constance Guillaud,1 Laure Croisille,6 Mohamed Jeljeli,7 Fréderic Batteux,7 Samia Baloul,4 Olivier Fain,5 France Pirenne,3 Jean-Claude Weill,2 Claude-Agnès Reynaud,2 Bertrand Godeau1,3
and Marc Michel1,3
*IA and EC contributed equally as co-second authors
1Service de Médecine Interne, Centre National de Référence des Cytopénies Auto- Immunes de l’Adulte, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris Est Créteil (UPEC), Créteil; 2Institut Necker Enfants Malades, INSERM U1151 CNRS UMS 8253, Université Paris Descartes, Sorbonne Paris Cité, Paris; 3Equipe n°2 "Transfusion et Maladies du Globule Rouge", EFS Île-de-France, IMRB U955 INSERM, Hôpital Henri-Mondor, AP-HP, Créteil; 4CEpiA (Clinical Epidemiology and Ageing), EA 7376-IMRB, Université Paris Est Créteil (UPEC), Hôpital Henri-Mondor, AP-HP Department of Public Health, Clinical Research Unit (URC- Mondor), Créteil; 5Sorbonne Université, Service de Médecine Interne, Hôpital Saint- Antoine, Assistance Publique-Hôpitaux de Paris, Paris; 6Etablissement Français du Sang, Service d'Immunologie Plaquettaire, Hôpital Henri-Mondor, Créteil and 7Service d'Immunologie Biologique, Hôpital Cochin, AP-HP, INSERM U1016, Institut Cochin, Paris, France
ABSTRACT
B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at 1 year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single-arm, prospective phase IIb trial investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, 2 weeks apart, combined with five infusions of beli- mumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary end- point was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard defini- tion. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with com- plete response. When compared with a cohort of patients receiving rit- uximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T-follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety (clinicaltrials gov. Identifier: NCT03154385).
Ferrata Storti Foundation
Haematologica 2021 Volume 106(9):2449-2457
Correspondence:
MATTHIEU MAHÉVAS
matthieu.mahevas@aphp.fr
Received: May 18, 2020. Accepted: August 6, 2020. Pre-published: August 13, 2020.
https://doi.org/10.3324/haematol.2020.259481 ©2021 Ferrata Storti Foundation
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