Antibody based therapeutics for autoimmune hemolytic anemia

Expert Opin Biol Ther. 2023 Jul-Dec;23(12):1227-1237. doi: 10.1080/14712598.2023.2274912. Epub 2023 Dec 28.

Abstract

Introduction: Autoimmune hemolytic anemia (AIHA) treatment has been revolutionized by the introduction of target therapies, mainly monoclonal antibodies (MoAbs).

Areas covered: The anti-CD20 rituximab, which targets Ab production by B-cells, induces 80% of response in warm-type AIHA (wAIHA) and 50-60% in cold agglutinin disease (CAD). Other B-cell targeting MoAbs including ianalumab, povetacicept, and obexelimab are under active study. The anti-CD38 MoAb daratumumab has been used in several reports to target long-lived plasma-cells responsible for AIHA relapse, being effective even in multi-refractory cases. Anti-complement MoAbs will soon change the treatment paradigm in CAD; the anti-C1s sutimlimab rapidly increased Hb in more than 80% of the cases. Finally, MoAbs inhibiting the neonatal Fc receptor (FcRn), such as nipocalimab, can reduce the half-life of the pathogenic autoAbs, representing a promising treatment for wAIHA.

Expert opinion: MoAbs offer the potential to improve efficacy by reducing toxicity. However, there is a huge need for clinical trials exploring response duration rather than short-term efficacy. Complement inhibitors and anti-FcRns do not abrogate autoAb production and are being developed as long-term therapies. Thus, the combination of B-cell/plasma cell targeting drugs deserves to be explored. On the other hand, their rapid efficacy should be exploited for the acute AIHA phase.

Keywords: Warm autoimmune hemolytic anemia; cold agglutinin disease; daratumumab; rituximab; sutimlimab.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic, Autoimmune* / drug therapy
  • B-Lymphocytes
  • Complement Inactivating Agents / therapeutic use
  • Humans
  • Infant, Newborn
  • Rituximab / therapeutic use

Substances

  • Rituximab
  • Complement Inactivating Agents