In two early trials, blood cancer treatment appears promising for deadly brain tumor

Two early trials published Wednesday showed promise in treating one of the deadliest types of cancer, glioblastoma.

The aggressive brain cancer, which took the lives of John McCain and Beau Biden, is only diagnosed at stage 4, and the five-year survival rate is around 10%.

The disease has no cure and, according to Dr. Michael Vogelbaum, chief of neurosurgery and program leader of neuro-oncology at Moffitt Cancer Center in Tampa, Florida, there have been no new drug approvals in the past two decades that have extended the lives of patients with glioblastoma.

The two clinical trials published Wednesday were extremely small, conducted on just nine patients in total, and much more research is needed, with larger trials, to determine how effective the therapy might be in the long run.

“All of these results are preliminary but encouraging,” said Vogelbaum, who wasn’t involved with either trial.

In the two unrelated trials, a novel take on an existing treatment for blood cancer was shown to be safe and it shrank tumors –– at least temporarily.

Both studies looked at the effects of a personalized immunotherapy called chimeric antigen receptor T-cell therapy — CAR-T therapy for short — in patients whose glioblastoma had returned after their initial treatment.

CAR-T therapy involves harvesting a person’s own immune cells and modifying them in a lab to seek out specific tumor proteins. The cells are then reintroduced into the body where they replicate, creating a surge of cancer-fighting immune cells.

The treatment is highly effective for certain blood cancers, but scientists are still studying whether modified versions of CAR-T therapy can be used for solid tumors like glioblastoma. These tumors, which account for the majority of cancers, present challenges that blood cancers do not.

Many blood cancers are homogeneous, meaning their cells are uniform. This gives CAR-T therapy a clear target to latch onto and attack. But solid tumors tend to have a variety of different cell types that can differ within individual tumors. This is particularly true for glioblastoma, which contains a large number of abnormal-looking cells.

“We had previous experience using a regular CAR in brain tumors but it wasn’t enough,” said Dr. Marcela Maus, director of the Cellular Immunotherapy Program at the Massachusetts General Cancer Center in Boston. Maus led one of the new studies, the results of which were published in The New England Journal of Medicine.

The original studies testing CAR-T therapy for glioblastoma only had one target, which is how the therapy has worked in blood cancers.

The cells targeted a protein with a specific mutation, but Maus said that not everyone with glioblastoma had the mutation. What’s more, even in patients who had the mutation, not every one of their tumor cells necessarily had it. “Even if we got the right cells, we didn’t get all of them because other tumors had other targets,” she said.

Expanding an existing therapy

Both phase 1 clinical trials used CAR-T cells that were programmed to attack two targets instead of one, with the hope that multiple targets would better equip the cells to destroy solid tumors.

“It gives you more shots on goal, at targeting the protein, because these are not completely overlapping targets on any given tumor,” said Dr. Vincent Lam, an assistant professor of oncology at the Johns Hopkins Cancer Center, who specializes in immunotherapies and wasn’t involved with either trial.

In Maus’ clinical trial, which included three patients, T-cells were engineered to seek out and attack a protein called EGRF that’s often found in abundance in glioblastoma tumors but is not present in healthy brain tissue. The second target was a variant of EGRF that’s also commonly found in the tumors.

When used to treat blood cancer, CAR-T cells are transferred back into the body intravenously. Maus’ team chose a more targeted approach for their experimental therapy: injecting the cells directly into the cerebrospinal fluid that surrounds the brain and spinal cord.

This prompted more of the cancer-fighting cells to stick around the site of the brain tumors and, the researchers hypothesized, would reduce the amount of the immunotherapy elsewhere in the body.

Confining the therapy to the brain was important: While the target, EGFR, is not found in healthy brain tissue, it is found in healthy cells elsewhere in the body. If the CAR-T cells went beyond the brain, they could potentially attack these cells.

To further prevent the CAR-T cells from escaping, the researchers bulked them up by binding them to an antibody, which made it more difficult for the cells to cross the blood-brain barrier and enter the bloodstream.

All three patients — two who were in their 70s and one in her late 50s — responded quickly to the treatment. Brain scans showed their tumors shrunk significantly within a day of receiving the therapy. In the 57-year-old woman, an MRI taken five days after her infusion of the modified cells showed her tumor was nearly gone.