Robert J. Kreitman, MD
Although long-term remissions are common in patients with hairy cell leukemia (HCL) who are treated with standard therapies, there remains an unmet need for novel agents that can eradicate the disease without excessive myelosuppression, according to Robert J. Kreitman, MD.
, Kreitman discussed key attributes of moxetumomab pasudotox and its potential impact in HCL. He is a senior investigator in the Laboratory of Molecular Biology and head of the Clinical Immunotherapy Section at the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland.
OncLive: Please explain the mechanism of action of moxetumomab pasudotox.
Moxetumomab pasudotox is an engineered protein drug—not a chemical— made up of a fragment of an antibody that binds to CD22 as well as a fragment of a toxin that’s made by Pseudomonas
bacteria. This purifies chimeric protein because it’s made up of 2 parts. One part of the drug binds to the hairy cell and allows the drug to go inside the cancer cell, while the bacteria enters the hairy cell and kills it. It does that through the same mechanism that any bacteria uses to kill a cell, so it’s highly potent.
The ultimate goal of the trial was to achieve complete remission with a resolution of normal blood counts, as blood counts are often low in patients with HCL at baseline. Patients who were minimal residual disease [MRD]–positive achieved complete remissions that lasted a median of 5.9 months, but investigators observed a significantly prolonged median duration of response for those who were MRD-negative by comparison.
What is the current prognosis for patients with HCL?
While many patients with HCL experience a remission with current treatments, 30% to 40% will relapse 5 to 10 years after their first treatment. With subsequent treatments, durations of response diminish and toxicities accumulate, and few approved treatment options exist. Moxetumomab pasudotox represents a promising nonchemotherapeutic agent for HCL.
How do patients tolerate moxetumomab pasudotox?
For patients with HCL, this is a very good drug. Patients need to be able to drink plenty of water and plenty of fluids to keep them feeling healthy during the time that they’re getting the drug, but most patients say that this drug is a walk in the park compared with chemotherapy or even rituximab [Rituxan], where there are significant infusion toxicities. We also can use very low doses of dexamethasone, a steroid, to treat fever, which sometimes arises in some patients.
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