Abstract
Hairy cell leukemia (HCL) is an indolent B-cell malignancy with excellent initial response to purine analogs pentostatin or cladribine, but patients are rarely, if ever, cured. Younger patients will usually need repeat chemotherapy which has declining benefits and increasing toxicities with each course. Targeted therapies directed to the BRAF V600E mutation and Bruton’s tyrosine kinase may be helpful, but rarely eradicate the minimal residual disease (MRD) which will eventually lead to relapse. Moxetumomab pasudotox (Moxe) is an anti-CD22 recombinant immunotoxin, which binds to CD22 on HCL cells and leads to apoptotic cell death after internalization and trafficking of the toxin to the cytosol. Phase I testing achieved a complete remission (CR) rate of 57% in relapsed/refractory HCL. Most CRs were without MRD and eradication of MRD correlated with prolonged CR duration. Patients were often MRD-free after five years. Important mild-moderate toxicities included capillary leak and hemolytic uremic syndromes which could be prevented and managed conservatively. A phase 3 trial met its endpoint of durable CR with acceptable toxicity, leading to FDA approval of Moxe for relapsed/refractory HCL, under the name Lumoxiti. Moxe combined with rituximab is currently being evaluated in relapsed/refractory HCL to improve the rate of MRD-free CR.
Highlights
Introduction to Hairy Cell LeukemiaHairy cell leukemia (HCL) is a B-cell malignancy comprising 2% of leukemias [1,2], amounting to about 1200 new cases per year in the United States [3]
First-line treatment of HCL underwent a major advance in the late 1980s with the use of purine analogs pentostatin or cladribine, each capable of achieving complete remission (CR) in 76–91% of patients [17,18,19,20,21,22,23]
It may still be difficult to determine whether the presence of residual disease and cytopenias indicate the need for additional treatment
Summary
Hairy cell leukemia (HCL) is a B-cell malignancy comprising 2% of leukemias [1,2], amounting to about 1200 new cases per year in the United States [3]. Other mutations have been reported in classic HCL, in association with BRAF V600E [8,9,10]. First-line treatment of HCL underwent a major advance in the late 1980s with the use of purine analogs pentostatin or cladribine, each capable of achieving complete remission (CR) in 76–91% of patients [17,18,19,20,21,22,23]. First-line treatment of HCL remains single-agent purine analog [26,27], repeat use is associated with declining CR rates, shorter disease-free intervals, and increasing risk of toxicity with each course, from chronic T-lymphopenia and neuropathy [28,29,30,31]. Outcomes using single-agent purine analogs are much poorer with variants of HCL [33,34,35], highlighting the importance of a correct initial diagnosis
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