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 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.