Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial

作者：Matthieu Mahévas, Imane Azzaoui, Étienne Crickx, Florence Canouï‐Poitrine, Delphine Gobert, Laetitia Languille, Nicolas Limal, Constance Guillaud, Laure Croisille, Mohamed Jeljeli, Frédéric Batteux, Samia Baloul, O. Fain, France Pirenne, Jean-Claude Weill, Claude–Agnès Reynaud, Bertrand Godeau, Marc Michel · 发表于：Haematologica · 年份：2020 · DOI：10.3324/haematol.2020.259481 · 被引用次数：62 · 研究领域：Platelet Disorders and Treatments、Blood groups and transfusion、Chronic Lymphocytic Leukemia Research

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 one 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 2b trial (RITUX-PLUS, NCT03154385) investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, two weeks apart, combined with five infusions of belimumab, 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 endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. 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 complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T follicular h...