Autoimmune hemolytic anemia - progress in emerging treatment options

ABSTRACT

Introduction: AIHA is a complex and heterogeneous disease involving antigen-autoantibody reaction, T-cell co-stimulation, complement activation, phagocytosis and bone marrow compensatory response. Several drugs targeting these mechanisms are under development in addition to standard therapies: steroids, immunesuppressors and splenectomy.

Areas covered: Rituximab is the first biologic therapy used in AIHA, and its association with bendamustine and fludarabine has been shown more effective in relapse/refractory cold agglutinin disease. In these cases bortezomib was also beneficial with an overall response in about 30% of cases, and several complement inhibitors (eculizumab, BIVV009, and APL-2) are currently under investigation. B-cell receptor inhibitors (ibrutinib, acalabrutinib, and idelalisib) are promising therapeutic options for lymphoproliferative associated secondary forms. Finally, targeting IgG driven extravascular hemolysis (SYNT001 and fostamatinib) is an exciting new treatment approach.

Expert opinion: AIHAs have been historically considered benign and easy to treat, however relapsing/refractory cases represent a clinical challenge. In these cases a target therapy would be ideal as traditional treatments are often ineffective/unfeasible. Moreover, the several mechanisms involved may be variably acting in the single patient and unpredictably changing overtime. Since several exciting target-therapies are emerging, only prospective studies would clarify the best choice, association, and sequence of these new drugs.

KEYWORDS:

• Autoimmune haemolytic anemia
• cold agglutinin disease
• complement
• rituximab

Article highlights

• AIHA is benign but more than one third of patients relapses and requires further treatment.

• Current therapy lines often give unsatisfactory responses in relapse/refractory cases.

• The pathogenesis of AIHA is far beyond antigen/autoantibody reaction and includes complement cascade and phagocytosis activation.

• New drugs targeting these multifaceted pathogenic steps are under investigation.

• Targeting the final haemolytic steps (complement/phagocytosis) will be particularly interesting in the chronic/relapsing cases and in the acute phase.

• A cooperative effort will be necessary to evaluate the new drugs in this rare and heterogeneous disease.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper is not funded