Effect of obexelimab on the production of anti-RBC antibodies and cytokines in patients with warm autoimmune hemolytic anemia

Obexelimab is a bifunctional, nondepleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit the activity of B-lineage cells. It is currently being evaluated in humans with various autoimmune diseases, including warm autoimmune hemolytic anemia (wAIHA). In this study, we evaluated the in vitro effect of obexelimab on the production of anti–red blood cell (anti-RBC) autoantibodies and cytokines in blood samples collected from a cohort of patients with wAIHA followed at a single tertiary hematological center. Obexelimab reduced the production of anti-RBC autoantibodies by 25% in unstimulated cultures and by 5% to 10% in phytohemagglutinin (PHA)-stimulated cultures, both at 15 and 405 μg/mL. In pokeweed (PWM)-stimulated cultures, obexelimab reached an inhibition of 35% at 405 μg/mL. Obexelimab (15 μg/mL) reduced interleukin-10 (IL-10) production in PHA-stimulated cultures from patients with wAIHA. Moreover, it induced an increase in interferon gamma, IL-2, and IL-17 production (∼20%-30%) and a milder increase in tumor necrosis factor α, IL-10, and transforming growth factor β (∼10%), in PWM-stimulated cultures. Soluble receptor IL-2Ra was slightly reduced and apoptosis antigen 1/FAS was minimally increased in PWM-stimulated blood cell cultures treated with obexelimab (15 μg/mL). Collectively, these findings support the notion that obexelimab exerts an immunomodulatory effect on RBC-specific autoantibody and cytokine production in wAIHA.