From OncoLog, July 2011, Vol. 56, No. 7
Inotuzumab Ozogamicin Shows Promise for Acute Lymphoblastic Leukemia Treatment
Promising results from a clinical trial of a new targeted therapy for acute lymphoblastic leukemia (ALL) were presented at the 2011 annual meeting of the American Society of Clinical Oncology by MD Anderson researchers.
In this ongoing trial led by Hagop Kantarjian, M.D., a professor in and chair of the Department of Leukemia, researchers tested the effectiveness of inotuzumab ozogamicin for treating therapy-resistant or refractory ALL. They found the drug to be surprisingly effective.
Of 46 patients evaluable for response, 9 had a complete response, 14 had a complete response without full recovery of platelets, and 5 had less than 5% blasts in their bone marrow without platelet recovery.
“A response rate of more than 50% in this patient population probably makes inotuzumab ozogamicin the most active single-agent therapy ever for ALL,” said Dr. Kantarjian. Many second-line treatment options for ALL offer response rates of only 20%–30%.
Inotuzumab ozogamicin is the first drug of its kind for the treatment of ALL. The drug is a combination of a monoclonal antibody that targets ALL cells and of calicheamicin, a powerful cytotoxic agent.
Because ALL arises from lymphoblasts, which are the bone marrow precursors to lymphocytes, most ALL cells express CD22, a marker of lymphocytic development. This molecule is the target of inotuzumab ozogamicin’s antibody component.
When inotuzumab ozogamicin binds to CD22, both calicheamicin and CD22 are taken up by ALL cells. Once inside a cell, calicheamicin, an antibiotic, readily cleaves the cell’s DNA to induce cell death. In this way, inotuzumab ozogamicin selectively kills the cancer cells while sparing most healthy cells.
In the study, most of the side effects of inotuzumab ozogamicin were mild or manageable; the most common side effect was fever. This safety profile and the high response rate make the drug promising for future trials. In fact, a phase II clinical trial that combines inotuzumab ozogamicin with rituximab, another antibody-based chemotherapy drug that targets leukemia cells, is already under way.
Future clinical trials may be needed to examine different dosing schedules for inotuzumab ozogamicin, which was given every 3 weeks in the initial study. The researchers suggested that weekly administration may increase the effectiveness of the drug.
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