Refractory and relapsed hairy-cell leukemia (HCL): casting light on promising experimental drugs in clinical trials

Expert Opin Investig Drugs. 2023 Apr;32(4):311-324. doi: 10.1080/13543784.2023.2193323. Epub 2023 Mar 23.

Abstract

Introduction: Hairy cell leukemia (HCL) is a rare subtype of indolent lymphoid leukemia originating from a mature B lymphocyte. The standard first-line treatment for classic HCL, and HCL variant (HCLv), consists of purine nucleoside analogs (PNA), with or without rituximab. However, almost half of patients relapse and require subsequent therapy.

Areas covered: This article summarizes recent achievements in the treatment of relapsed and refractory HCL. A literature search was conducted of the PubMed and MEDLINE database for articles in English. Publications from 2010 through January 2023 were scrutinized. The search terms used were hairy cell leukemia in conjunction with BRAF inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, CD20 monoclonal antibodies, relapsed, refractory and variant.The growing understanding of HCL biology has allowed the design of several new, chemotherapy-free targeted drugs which have demonstrated encouraging efficacy in early clinical trials.

Expert opinion: Novel drugs will soon be available to assist standard therapy for HCL and HCLv among patients with suboptimal results following PNA treatment. In particular, the BRAF inhibitors vemurafenib and dabrafenib, with or without rituximab, have revolutionized treatment of patients with relapsed or refractory disease.

Keywords: BRAF; dabrafenib; hairy cell leukemia; ibrutinib; moxetumomab pasudotox; novel drugs; trametinib; variant; vemurafenib.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Leukemia, Hairy Cell* / drug therapy
  • Proto-Oncogene Proteins B-raf
  • Recurrence
  • Rituximab / therapeutic use

Substances

  • Antineoplastic Agents
  • Rituximab
  • Proto-Oncogene Proteins B-raf