Zanubrutinib for the treatment of relapsed/refractory hairy cell leukemia
Constantine S. Tam, Judith Trotman, Stephen Opat, J. C. Stern, Heather Allewelt, Kunthel By, William Novotny, Jane Huang, Alessandra Tedeschi
Abstract
Hairy cell leukemia (HCL) is a rare, indolent B-cell malignancy comprising 1.4% of all lymphoid neoplasms, with 1910 new cases in the United States in 2016. 1 Patients generally present with cytopenias, splenomegaly, and an increased risk of infections.Newly diagnosed patients are treated with purine nucleoside analogs (PNAs), which have demonstrated efficacy in HCL-overall response rate (ORR) of 97% and median relapse-free survival of 16 years. 2For patients who do not respond to PNAs or who relapse quickly or after therapy for relapsed/refractory disease, the preferred treatment strategies include clinical trial participation, retreatment with a PNA plus rituximab, moxetumomab pasudotox, vemurafenib with or without rituximab, peginterferon-alfa 2a, or ibrutinib. 3Patients with 2 or more relapses will continue to relapse, with steadily decreasing durations of response. 4Thus, additional targeted therapies are needed.Zanubrutinib (BGB-3111) is a second-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target inhibition of TEC-and EGFR-family kinases.It has demonstrated efficacy in a various B-cell malignancies and has a favorable safety profile. 5,6We report the outcomes of 12 patients with relapsed/refractory HCL treated with single-agent zanubrutinib in a phase 1/2 open-label study (NCT02343120).