Autoimmune hemolytic anemia - progress in emerging treatment options. (3rd April 2018)

• Record Type: Journal Article
• Authors: Barcellini, Wilma; Fattizzo, Bruno
• Is Part Of: Expert opinion on orphan drugs. Volume 6:Number 4(2018)
• Page Start: 273
• Page End: 282
• Publication Date: 2018-04-03
• Subjects: Autoimmune haemolytic anemia -- cold agglutinin disease -- complement -- rituximab; Orphan drugs -- Periodicals; Rare diseases -- Periodicals; Chemotherapy -- Periodicals; 615.1
• DOI: 10.1080/21678707.2018.1452734
• Languages: English
• ISSNs: 2167-8707

Abstract

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.