Peter Valadez suffered from aggressive, recurrent glioma. A Phase 1 clinical trial using CAR T cell therapy was his last hope.
In 2014, Peter Valadez had a nagging neck pain that wouldn’t go away. Doctors thought it was a mastoid infection and prescribed antibiotics.
But the pain persisted. Valadez, then 48, was on a phone call at the advertising agency where he worked in Anaheim, California, when he felt tingling in his fingers. The person he was talking to told him to get to an emergency room.
There, Valadez received a computer tomography scan, which revealed a brain tumor — a high-grade glioma — in the middle part of his brain.
One doctor told him he had six months to live and added: "You better get your affairs together. Let your kids know they're going to have to pay their own way through college."
Entering a Glioma Clinical Trial
“It was a pretty tough blow to be told that he had cancer,” Josie Valadez, Peter’s wife, recalled. “He never had any other symptoms. When they performed the surgery, the cancer was as large as a baseball.”
Valadez also received radiation and chemotherapy. The cancer stayed in remission for a year. Surgeons again removed a tumor, and Valadez received chemotherapy. Six months later, the cancer returned.
“It was coming back faster and faster,” Josie said.
By then, the Valadezes had heard about immunotherapy. Doctors at other hospitals told the couple they had no other treatments for Valadez, and there was a 98% chance the cancer would return.
They encouraged the couple to call City of Hope, a nationally recognized leader in chimeric antigen receptor (CAR) T cell therapies for glioblastoma and other cancers. The cancer center has treated more than 1,200 patients since its CAR T program started in the late 1990s and continues to have one of the most comprehensive CAR T cell clinical research programs in the world — it currently has about 70 ongoing CAR T clinical trials, which include 13 different solid tumor types.
A Game-Changing Phase 1 Trial
In summer 2018, Valadez qualified for a City of Hope trial that used chimeric antigen receptor (CAR) T cell therapy developed by scientists there, a pioneering Phase 1 CAR T cell therapy trial for the treatment of brain cancers. Results from the trial, which is the largest reported trial to date of CAR T therapy for solid tumors, were published today in the journal Nature Medicine.
Twenty-nine of the 58 patients with recurrent high-grade glioma brain tumors, mostly glioblastoma, achieved stable disease after treatment with CAR T cells for at least two months. There were two partial responses, one complete response (in Valadez), and a second complete response after additional CAR T cell therapy cycles were delivered under compassionate use.
The CAR T cell therapy used Valadez’s own T cells to fight cancer. In a City of Hope laboratory, his cells were reprogrammed to recognize and attack a specific protein found in brain tumors then reintroduced back into his system.
Behnam Badie, M.D., the trial’s principal investigator and City of Hope chief of neurosurgery, explained that one of the main challenges for treating brain cancer is that medications have difficulty crossing the blood-brain barrier. To overcome that barrier, City of Hope scientists — led by Christine Brown, Ph.D., The Heritage Provider Network Professor in Immunotherapy and deputy director of the T Cell Therapeutics Research Laboratories at City of Hope — also developed a technique that allowed patients such as Valadez to receive CAR T cells directly into the brain tumor and the cerebrospinal fluid, the fluid that protects and surrounds the brain and spinal cord.
“It was a pleasure caring for Peter,” said Badie, The Heritage Provider Network Professor in Gene Therapy. “Despite what he was going through, Peter and Josie always had a positive but realistic attitude toward his therapy and life in general.”
Glioma Remission
“I just remember a needle going in my head,” said Valadez, who first had the tumor surgically removed and then received the CAR T cells. "A big, giant, horse needle.”
Valadez, who said he did not experience any pain receiving the CAR T cell therapy, did so well after receiving six infusions of CAR T cells that the family was able to travel to Hawaii. But about six months after the therapy, Valadez experienced wound breakdown, the result of numerous surgeries and radiation therapy, and his cerebrospinal fluid started to leak profusely. He developed four scalp infections that City of Hope doctors also treated.
City of Hope surgeon Wai-Yi Li, M.D., Ph.D., also performed plastic surgery on Valadez, removing skin from other areas of his body to cover the surgical incisions on his head.
'CAR T Saved His Life'
The fluid stopped leaking and for the past five and a half years, magnetic resonance imaging has shown that his brain cancer is in remission. Valadez’ left side is partially paralyzed, but he can walk slowly with a cane.
Although it has been a difficult journey for the Valadez family, Josie, who has been married to Valadez for 31 years, said she is grateful.
“CAR T saved his life,” she said.
Valadez, 58, is the father of three grown children and the grandfather of a 4-year-old granddaughter. Since his cancer diagnosis, he has been able to witness many milestones in his children’s lives, including his youngest daughter’s high school graduation, a son’s college graduation, a son’s marriage and the joy of being a grandfather.
“I tell Peter that he is here with us to celebrate milestones, to see his kids grow up and, now, to see his grandchild,” Josie added. Prior to the cancer diagnosis, she recalled that Valadez made a lot of money as an advertising agency executive.
“We were so worried about getting the next best car or the next boat or the next house,” she added. “And all of that went away when this happened to him.”
The cancer diagnosis “never once detoured us from our faith,” she added. “We became closer to God through all of this. It gave us a whole new perspective on life. At the end of the day, I tell him, you're going to see our youngest daughter get married. You may not be able to walk her down the aisle in the way that you thought you could, but you're still going be there with her.”
For his part, Valadez said he is proud to have been part of a pioneering clinical trial that he hopes will make it possible for more immunotherapies to be developed for brain cancer patients.
“Hopefully, my treatment can help save the lives of young people,” he said.
(Credit: Letisia Marquez- City of Hope)
