(ChemotherapyAdvisor) – The anti-CD22 recombinant immunotoxin moxetumomab pasudotox has shown activity in patients with chemotherapy-resistant hairy cell leukemia (HCL) and has a safety profile supporting further clinical development, results of a Phase 1 study published in the Journal of Clinical Oncology online February 21, 2012, have shown.

The dose-escalating study enrolled 28 patients, three each at 5, 10, 20, and 30µg/kg, four patients at 40µg/kg, and 12 patients at 50µg/kg three times daily for 1–16 cycles each (median, 4 cycles). No dose-limiting toxicities were observed; two patients had transient laboratory abnormalities consistent with grade 2 hemolytic uremic syndrome. The grade 1/2 toxicities that occurred in 25% to 64% of patients were, in decreasing frequency, “hypoalbuminemia, aminotransferase elevations, edema, headache, hypotension, nausea, and fatigue,” the investigators noted.

Ten of the twenty-six patients (38%) evaluable for immunogenicity produced antibodies that neutralized >75% of the cytotoxicity of 1,000ng/mL of immunotoxin; however, this immunogenicity was rare (5%) after cycle 1, they noted.

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Responses were observed at all dose levels. Overall response rate was 86%. Complete remission (CR) was observed in 13 patients (46%). These CRs were durable and without evidence of minimal residual disease; only one lasted <1 year. “CRs were achieved only in patients without prior splenectomy,” they wrote. Median disease-free survival was not reached at 26 months.

“We believe these Phase I results support a pivotal trial in which patients with multiply relapsed HCL are randomly assigned between moxetumomab pasudotox and best alternative therapy (ie, rituximab or cladribine),” they noted. To further delineate efficacy and safety, patients with HCL are continuing to receive the 50µg/kg three times daily dosage. In addition, clinical trials are exploring the use of moxetumomab pasudotox for chronic lymphocytic leukemia and non-Hodgkin’s lymphoma in adults and acute lymphoblastic leukemia in children.