Experimental treatment shows early promise for advanced neuroblastoma in children

Tumors shrank or disappeared and disease progression was temporarily halted in 15 children with advanced neuroblastoma enrolled in a safety study of an experimental antibody. Four patients are still alive after more than 2.5 years and without additional treatment.

The results from this Phase I study, conducted at St. Jude Children's Research Hospital in Memphis, Tennessee, prompted St. Jude to expand clinical trials of the monoclonal antibody hu14.18K322A to include patients with newly diagnosed neuroblastoma. Monoclonal antibodies are engineered in an on-site laboratory so that they can recognize and attach to specific markers carried on the cell surface.

Neuroblastoma is a cancer of the sympathetic nervous system. It is the most common cancer diagnosed in the first year of life and accounts for 7% to 10% of childhood cancers. Certain patients, particularly infants, enjoy cure rates of 90% or better; however, the outlook is worse for high-risk patients, including those whose disease has spread widely. New treatments are urgently needed for these patients, less than half of whom currently enjoy long-term, disease-free survival.

"This was the first time this experimental antibody was tried in patients. We were encouraged with the response," said first and corresponding author Fariba Navid, MD, of St. Jude. "The percentage of patients who benefited from treatment with hu14.18K322A was unusual for a Phase I study."

In this study, 38 St. Jude patients received 1 of 9 different doses of hu14.18K322A. The immunotherapy is designed to activate the disease-fighting immune system to attack and kill tumor cells. Every 28 days, patients received an infusion of hu14.18K322A once daily for 4 days.

Of the 31 patients evaluated after two or more rounds of treatment, the disease stabilized in nine patients, tumors shrank in two patients, and were undetectable in four more. "Four patients are alive after more than two-and-a-half years without additional therapy," Navid said.

Hu14.18K322A is an antibody engineered to recognize and attach to a molecule called the GD2 antigen. GD2 is found on the surface of almost all neuroblastoma cells as well as other tumors, including the skin cancer melanoma, the bone cancer osteosarcoma, and soft-tissue sarcomas. The antigen is found on the normal cells of just a few tissues.

In this study, published in the Journal of Clinical Oncology (2014; doi:10.1200/JCO.2013.50.4423), pain remained the most common side effect associated with hu14.18K322A treatment. Although 68% of patients reported severe pain during the first round of treatment, Navid said the pain was manageable with medication and resolved within 24 hours of receiving the experimental antibody. The pain also lessened with each round of therapy.

Direct comparisons between patients who received hu14.18K322A and a different version of the antibody are difficult, but Navid said, "Our clinical impression is that the duration and severity of pain in patients receiving hu14.18K322A are less."

Clinical trials involving hu14.18K322A continue at St. Jude. Researchers are testing the impact of giving the monoclonal antibody weekly rather than every 28 days and in combination with other therapies.

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