Orphan drugs for the treatment of hairy cell leukemia

Abstract

Introduction: Hairy cell leukemia (HCL) is a rare leukemia derived from mature B lymphocytes. Advances in the understanding of its pathogenesis have translated into the development of effective therapies. Interferon was the first agent that showed activity in HCL. However, most responses were partial and after stopping the drug, relapses occurred. The introduction of 2-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (CDA) represented a major progress in the management of HCL. Responses to these agents are seen in 95% of patients and > 75% are durable complete responses. However, 40% of patients relapse and although a second response may be achieved, this is of shorter duration. In such setting, strategies using Rituximab targeting CD20 combined with DCF or CDA and/or immunotoxins such as the anti-CD22 McAb linked to the truncated pseudomonas exotoxin have shown promising results in relapsed patients. The recent discovery of the presence of BRAF mutations in HCL has opened avenues for targeting this deregulated gene with BRAF inhibitors. Areas covered: This manuscript summarises the disease features, pathogenesis, diagnosis and current and new targeted treatments for HCL. A literatura search on pub med has been undertaken and the most relevant references have been considered. Expert opinion: HCL is a potentially curable disease with the available treatments. DCF or CDA should be the standard first line treatment. Patients with suboptimal responses to these drugs or multiple relapses should be treated with Rituximab plus DCF or CDA or immunotoxins.