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Abstract
Standard treatment for hairy cell leukemia (HCL) is markedly effective, but the constant decrease in disease-free survival, together with the presence of minimal residual disease (MRD), suggests that few if any are cured. HCL cells in MRD are always strongly CD20 + and CD22 + , and also CD25 + unless the patient has the poor-prognosis variant HCLv. To target relapsed/refractory HCL, immunotherapy has been developed using anti-CD25 and anti-CD22 recombinant immunotoxins, or the anti-CD20 monoclonal antibody (mAb) rituximab alone or combined with purine analogs. The recombinant immunotoxins contain an Fv fragment of a mAb fused to a truncated form of Pseudomonas exotoxin called PE38. BL22 targeting CD22, in phase I and II testing of relapsed/refractory HCL, achieved 47–61% complete remissions (CRs), several of them ongoing after 9–10 years. A completely reversible form of hemolytic uremic syndrome (HUS) was observed in 12% of patients, several of whom could later achieve a partial remission (PR) or CR with LMB-2 targeting CD25. A higher-affinity version of BL22, termed HA22, CAT-8015, or moxetumomab pasudotox, developed to more effectively treat other hematologic malignancies, also achieves CRs in HCL, and with only non-dose-limiting HUS. In separate randomized trials, rituximab is undergoing phase II testing with cladribine for early HCL and with bendamustine or pentostatin for multiply relapsed HCL.
Acknowledgements
This work was supported in part by the National Cancer Institute, Intramural Program. Work regarding moxetumomab pasudotox (HA22 or CAT-8015) and BL22 (CAT-3888) was supported in part by MedImmune, LLC.
Potential conflict of interest:
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