Treatment of autoimmune hemolytic anemia: novel and investigational approaches

Autoimmune hemolytic anemia (AIHA) is a heterogeneous group of diseases. While corticosteroids remain first-line therapy for the warm-antibody types (wAIHA), they are ineffective in cold agglutinin disease (CAD). During the last couple of decades, several new established or investigational treatment options have appeared. These advances have resulted in improvements of therapy, but also raised new challenges.

This review aims at providing an update on AIHA treatment with focus on novel and investigational approaches. PubMed was searched for original research articles and reviews from 2000 through 2024. Selected case reports, published congress presentations, book chapters, and older articles were included when considered relevant.

Pathogenetic features and diagnostic workup in AIHA are briefly outlined, and existing therapies for the respective subtypes are reviewed. The evidence for new documented therapies is described, including erythropoietin, fostamatinib, and bortezomib-based combinations in wAIHA; and complement-directed therapies in CAD. Investigational and experimental therapies are also addressed, including inhibitors of the neonatal Fc receptor, cytokine inhibitors, complement blockers, Bruton tyrosine kinase inhibitors, and plasma cell-directed approaches in wAIHA; and Bruton tyrosine kinase inhibitors, plasma-cell directed therapies, novel complement inhibitors, cytokine antagonists, and novel monoclonal antibodies in CAD.

Exact diagnostic workup is critical for selection of optimal therapy in AIHA. While therapy is becoming increasingly evidence-based, several unmet needs remain. The ideal therapy has not been found for wAIHA or CAD, and evidence-based options are largely lacking for the still rarer subtypes. Patients with AIHA should be considered for clinical trials.