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.