By: Amy Norton
Children with the rare cancer neuroblastoma often succumb to the disease despite aggressive treatment. But researchers have found that adding an experimental antibody to that treatment, right off the bat, may improve their outlook.
Of 64 children treated with the antibody in a clinical trial, 74% were still alive and free of a recurrence three years later. That compares with historical rates of around 50% with conventional treatment alone.
The antibody, known as hu14.18K322A, remains experimental, and is not yet available as a treatment, said Dr. Wayne Furman, the lead researcher on the trial.
The Children’s Oncology Group, a government-funded clinical trials group, is planning a larger study to test the tactic of early antibody therapy — with either hu14.18K322A, or another drug, Furman said.
Neuroblastoma is a cancer that begins in immature nerve cells, and primarily affects babies and children younger than 5. Each year, about 800 children in the United States are diagnosed with the disease, according to the American Cancer Society.
Roughly half of them are diagnosed after the cancer has spread and is considered “high risk.”
At that point, aggressive treatment is needed. The typical regimen starts with high-dose chemotherapy, followed by surgery to remove any remaining visible tumors. Next comes additional chemo, followed by a stem cell transplant to rebuild the immune system, and then radiation.
In more recent years, doctors have added another weapon to the end of that regimen: the monoclonal antibody drug dinutuximab. The drug latches onto GD2, a protein on the surface of many neuroblastoma cells. It’s given along with certain immune system proteins, in the hopes of boosting the child’s immune response to cancer cells that have survived the treatment onslaught.
Dinutuximab has made a difference: One trial found that after two years, 66% of children given the drug were recurrence-free, compared with 46% of those on standard treatment alone.
But dinutuximab has been given at the tail end of treatment, said Furman, an oncologist at St. Jude Children’s Research Hospital in Memphis, Tenn.
That was based on the belief that giving it early, during the initial high-dose chemo, would zap its effectiveness — because the chemo suppresses the immune system.
“But we’ve been learning more and more about the immune system,” Furman said.
Studies of adults with certain cancers, for example, have found that combining antibody therapy with chemo — a concept called chemoimmunotherapy — improved patients’ responses. And a recent Children’s Oncology Group trial found that adding dinutuximab to chemo showed “significant anti-tumor activity” in children whose neuroblastoma had come back.
Furman’s team reasoned that giving an anti-GD2 antibody straight away, instead of waiting, might do the same for children newly diagnosed with high-risk neuroblastoma.
Instead of dinutuximab, though, they used the experimental antibody, developed at St. Jude. It also targets GD2, but was designed to limit a primary side effect of dinutuximab: pain.
Children in the trial received six rounds of chemo, along with infusions of the antibody therapy. They then moved on to other standard treatments, including additional antibody infusions.
While the experimental antibody was designed to cause less pain, the children still needed infusions of opioid painkillers during treatment. Pain was the most common side effect tied to the antibody — reported in 10% of treatment cycles.
After three years, 86% of the children were still alive, with 74% recurrence-free.
Furman said that in 30 years of treating kids with high-risk neuroblastoma, those are the best outcomes he has seen.
It is not clear whether all of those recurrence-free children are cured; it’s possible the treatment delays recurrence in some, according to Furman. The hope, of course, is that the results hold up.
“This is a very important and provocative study building on recent advances with chemoimmunotherapy for children with relapsed neuroblastoma in the Children’s Oncology Group,” said Dr. John Maris, chairman of neuroblastoma research at Children’s Hospital of Philadelphia.
Like Furman, he pointed to the COG trial that will test the approach in newly diagnosed children.
“If confirmed, chemoimmunotherapy would become standard therapy and hopefully, significant improve chances for cure of high-risk neuroblastoma,” said Maris, who wasn’t part of the research.
Furman said children in his study received the experimental antibody at a dose more than double the maximum approved dose of dinutuximab. It’s unclear, he said, whether the children’s outcomes are related to the higher dose, or because hu14.18K322A is “a better antibody.”
The study — published Dec. 6 in Journal of Clinical Oncology, was funded by federal and foundation grants. The experimental antibody is now owned by EMD Serono, a division of drug maker Merck.