An antibody packaged with a potent chemotherapy drug to selectively destroy acute lymphoblastic leukemia (ALL) cells eradicated or greatly reduced the disease for 61 percent of 46 patients in a phase II study. It was presented at the 47th annual meeting of the American Society of Clinical Oncology.

Patients enrolled in the trial led by investigators at The University of Texas MD Anderson Cancer Center had ALL that resisted other therapies or recurred after treatment.

"A response rate of more than 50 percent in this patient population probably makes inotuzumab ozogamicin the most active single-agent therapy ever for ALL," said Hagop Kantarjian, M.D., professor and chair of MD Anderson's Department of Leukemia and study senior investigator.

The drug, also known as CMC-544, links an antibody that targets CD22, a protein found on the surface of more than 90 percent of ALL cells, and the cytotoxic agent calicheamicin. Once the drug connects to CD22, the ALL cell draws it inside and dies.

Response rate for other second options is 20-30 percent

Kantarjian said second-line chemotherapy combinations used for ALL typically have a complete response rate of 20-30 percent. The monoclonal antibody-based drug developed by Pfizer, Inc., also is the first of its type for ALL.

The drug is safe, said Elias Jabbour, M.D., assistant professor in MD Anderson's Department of Leukemia, presented the study results at ASCO. Almost all side effects were of low grade (1-2) and manageable. Drug-induced fever was the most common side effect, reaching higher grades in nine of 48 patients.

Out of 46 patients evaluable for response, nine had a complete response, 14 had complete response without full recovery of platelets, and 5 had less than 5 percent blasts in their bone marrow without blood count recovery.

Sixteen responders subsequently received a donor blood stem cell transplant, Jabbour noted.

Combining inotuzumab with other chemotherapy might further improve ALL treatment, Jabbour said. MD Anderson has a phase II clinical trial under way following inotuzumab treatment with another monoclonal antibody drug, rituximab, currently used in some types of non-Hodgkin's lymphoma.

Rituximab targets the CD20 surface protein, which occurs in 50 percent of ALL cells.

In addition to combinations, the authors suggest that a shift from dosing every three weeks to weekly should be explored.

The clinical trial was funded by a grant from Pfizer.

Co-investigators with Jabbour and Kantarjian are Susan O'Brien, M.D., Deborah Thomas, M.D., Farhad Ravandi, M.D., Sergernne York, Monica Kwari, Stefan Faderl, M.D., Tapan Kadia, M.D., Guillermo Garcia-Manero, M.D., and Jorge Cortes, M.D., of MD Anderson's Department of Leukemia; Christopher Wilson and Robert Tarnai, of PPD, Inc.; and Anjali S. Advani, M.D., of the Cleveland Clinic Taussig Cancer Institute.