Towards achieving immune reset in autoimmune cytopenias: Insights from clinical experiences with B cell depleting therapies

Autoimmune cytopenias (AICs) arise from pathogenic autoantibody-mediated destruction of blood cells. Current treatments often fail to achieve durable remission, necessitating long-term treatment including immunosuppression and exposure to treatment-related toxicities. Insights into B cell biology demonstrate the central role of autoreactive B cells and plasma cells in sustaining disease activity and relapse, providing a rationale to achieve sustained, treatment-free remissions through "immune reset". This review summarizes the current understanding of immune reset in AICs and examines clinical data for depletion strategies targeting distinct stages of B cell maturation. We compare therapeutic modalities across monoclonal antibodies, bispecific T cell engagers (TCE), and chimeric antigen receptor (CAR) T cells. The depth and breadth of depletion, kinetics of immune reconstitution, and treatment-related risks are critical determinants of long-term outcome potential and individualized risk-benefit assessment. Collectively, these advances support a potential paradigm shift from chronic immunosuppression towards durable remissions off therapy with time-limited therapeutic interventions.