Immunotherapy Improves Cure Rate for Children with Neuroblastoma


by Jen Uscher

August 6, 2009

Children with high-risk neuroblastoma who received a supplemental immunotherapy treatment in a recent study were 20 percentage points more likely to be disease-free two years later than those who received the standard therapy alone.

The results from adding the treatment—an antibody plus two immune-boosting hormones—were so significant that the research team decided to offer the treatment to its control-group patients as well. Their decision ended the randomization portion of the trial earlier than expected, says the study’s leader, Alice Yu, a professor of pediatric hematology and oncology at the University of California, San Diego, School of Medicine.

“Now we’re offering the immunotherapy to all the patients enrolled in the trial,” she says. “And soon it will be the new standard of care for patients with high-risk neuroblastoma.” She presented the research on June 2 at the annual meeting of the American Society of Clinical Oncology in Orlando, and it was posted on the society’s Web site in May.

A cancer that forms in developing nerve cells in the neck, chest, or abdomen, neuroblastoma is most commonly diagnosed in children under 5 years old. Doctors classify it by severity; about 40 percent of patients have the high-risk form. Curing this form of the disease is a “huge challenge,” says Brian Kushner, a pediatric oncologist at Memorial Sloan-Kettering Cancer Center who was not involved in the clinical trial.

“The patients typically have a tremendous tumor burden, with an enormous abdominal mass and substantial disease throughout the rest of the body,” he says. Many patients relapse after being treated; the long-term survival rate is 30 to 40 percent. “We’re glad the study showed such encouraging results with this new kind of treatment, which gets the body’s own immune system to attack the cancer.”

The new therapy consists of a monoclonal antibody called Ch14.18 and two cytokines, hormones that help to boost the immune system, called IL-2 and GM-CSF. The antibody targets a particular glycolipid on the surface of neuroblastoma cells called GD2. When the antibody binds to GD2, it triggers immune cells to attack the cancer cells.

The cytokines increase the number of immune cells and make them more potent. Other researchers have used different monoclonal antibodies (such as 3F8 and hu14.18) with cytokines to treat neuroblastoma, but the new regimen is the first randomized clinical trial to show success with such a treatment for high-risk neuroblastoma. This sort of randomized study is “the gold standard, the highest-value kind of study for a treatment,” Kushner says.

The Phase III (large-scale, human) clinical trial, conducted by the pediatric cancer research cooperative Children’s Oncology Group, included 226 children with high-risk neuroblastoma who had already received and responded to the standard treatment of surgery, intensive chemotherapy, a stem-cell transplant and radiation. Half the patients were randomly chosen to receive the standard drug therapy (isotretinoin, or Accutane); the other half also received the experimental immunotherapy treatment. Most of the patients in the study were between the ages of 2 and 5.

Two years after treatment, 86 percent of the children who received immunotherapy were still living, compared with 75 percent of those receiving only the standard treatment. Overall, 66 percent of the patients in the immunotherapy group were free of cancer compared with 46 percent of those who received only the traditional drug.

Yu says that the odds are good that the patients who are free of high-risk neuroblastoma two years after treatment are cured, since most relapses in these patients take place within the first two years after the stem-cell transplant part of the treatment.

The National Cancer Institute currently manufactures the monoclonal antibody. The Children’s Oncology Group researchers plan to continue to offer the treatment to the patients in the original trial, and they’re starting a new trial at selected medical centers to collect comprehensive toxicity and safety data so they can submit the drug for FDA approval.

The approach could potentially be tested for other types of cancer that express the GD2 molecule, including melanoma, small cell lung cancer, soft tissue sarcoma and some types of brain tumors, Yu says.