Leading new treatment research for neuroblastoma

DeSantes, a UW Carbone Cancer Center researcher and Medical Director for the Pediatric Bone Marrow Transplant and Cell Therapy program, said this phase I-II clinical trial uses a variation of an existing immunotherapy drug as part of a combination therapy for neuroblastoma patients who have advanced stage disease and have failed other treatments.

“This is a very high-risk patient population — usually they’ve failed a number of different therapies before they would come to participate in this study,” DeSantes said. “So it’s a very heavily-pretreated patient population to begin with.”

Neuroblastoma is one of the most common early childhood cancers, affecting immature nerve cells, called neuroblasts. In this combination approach, the molecule MIBG linked to iodine-131 is given as a targeted radiation therapy to sensitize neuroblastoma cells to immunotherapy treatment: nivolumab, a checkpoint inhibitor commonly used in adult cancer patients, and dinutuximab beta, which targets an antigen called GD2 that is expressed by neuroblastoma cells.

Dinutuximab beta is a variation of the dinutuximab that is currently approved for use in the U.S. The U.S. version is given intravenously for 4 to 20 hours a day for four consecutive days, and because healthy nerve cells also express GD2, the treatments are very painful. That’s why patients must be treated in-patient at the hospital.

“The kids are on morphine drips, or other very strong pain medications, for them to be able to tolerate this antibody,” DeSantes said.

In this clinical trial, dinutuximab beta is being given continuously by infusion over 10 days, reducing the painful side effects enough so that treatments often do not require a hospital stay.

“We give the first cycle (of this trial) in the hospital, and then if the patient tolerates it well, the rest of the therapy is given in the outpatient setting,” he said. “So the kids can be at home or be at school getting the antibody treatment, and we think it’s really a better way to treat kids with neuroblastoma because it’s just so much more tolerable.”

The foundational research that led to this clinical trial was conducted at UW, with Drs. Paul Sondel and Zachary Morris, of the Department of Human Oncology, among the key collaborators.

About 20 patients have participated in this research through UW’s trial as well as two trial sites in England. DeSantes said they hope to expand the trial to more patients to collect more data and further evaluate the treatment efficacy.

“It’s been an exciting trial,” he said. “We’ve had referrals from different parts of the country to participate in this study, since we’re the only site in the United States that has it open. And the results we’re seeing are encouraging, we’re seeing responses.”