Treatment of hairy cell leukemia

Purine analogs made dramatic improvements for patients with hairy cell leukemia (HCL), but patients often relapse, require multiple treatments, and may become refractory. Major developments in treatment of relapsed/refractory HCL occurred with discovery of disease biology. New agents increase the complexity of clinical decision-making.

Anti-CD22 recombinant immunotoxin Moxetumomab Pasudotox (Moxe), CD20 Mabs rituximab and obinutuzumab, BRAF/MEK inhibitors vemurafenib and dabrafenib-trametinib, and Bruton's tyrosine kinase (BTK) inhibitor ibrutinib have been tested in HCL. All show efficacy but with different treatment durations and response rates, including for eradicating minimal residual disease (MRD). Side effects differ and must be considered when selecting treatment. Studies from PubMed indexed papers and abstracts presented at major international conferences are included.

Rituximab with either purine analog or BRAF-inhibitor achieves high rates of MRD-free complete remission (CR). Moxe achieves MRD-free CR without chemotherapy toxicities. Moxe should be considered prior to splenectomy or development of adenopathy. BRAF/MEK inhibition and ibrutinib are effective options but most patients remain MRD+, requiring indefinite treatment or rituximab to prevent relapse. Under investigation is MRD elimination with CD20 antibody combined with Moxe or BRAF inhibitor. High-risk diseases including HCL variant and IGHV4-34+ unmutated HCL require further investigation.