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

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. Identifiera NCT03154385).

Automated summary

The combination therapy of rituximab and belimumab shows promise in preventing the emergence of long-lived plasma cells in ITP patients, leading to increased overall response rates at 1 year. The safety and efficacy of this combination therapy appear high, with a decrease in circulating T-follicular helper cells observed.