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Development of Recombinant Immunotoxins for Hairy Cell Leukemia

Laboratory of Molecular Biology, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
National Institutes of Health, Building 37/5124b, 9000 Rockville Pike, Bethesda, MD 20892, USA
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(8), 1140;
Received: 20 June 2020 / Revised: 22 July 2020 / Accepted: 24 July 2020 / Published: 3 August 2020
(This article belongs to the Special Issue Immunotoxins: From Design to Clinical Application)
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. View Full-Text
Keywords: hairy cell leukemia; treatment; rituximab; moxetumomab pasudotox; minimal residual disease hairy cell leukemia; treatment; rituximab; moxetumomab pasudotox; minimal residual disease
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MDPI and ACS Style

Kreitman, R.J.; Pastan, I. Development of Recombinant Immunotoxins for Hairy Cell Leukemia. Biomolecules 2020, 10, 1140.

AMA Style

Kreitman RJ, Pastan I. Development of Recombinant Immunotoxins for Hairy Cell Leukemia. Biomolecules. 2020; 10(8):1140.

Chicago/Turabian Style

Kreitman, Robert J., and Ira Pastan. 2020. "Development of Recombinant Immunotoxins for Hairy Cell Leukemia" Biomolecules 10, no. 8: 1140.

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