Kaleb Warman looks and feels great. A senior at Upland High School (about 40 miles east of Los Angeles), the 6’2”, 250 lb. right tackle loves playing for the Highlanders/Scots, his varsity football team. His newly light blond hair makes you think of a young Robert Redford. Of course, mention that name and Dad chimes in, smiling, “He doesn’t know who that is!”
At 17, Kaleb is happily enjoying the full bloom of his final year in high school, which is exactly what he and his family wanted. That’s why they made a critical decision when Kaleb unexpectedly developed a problem a year earlier. And, it turns out, their decision not only helped Kaleb, but will benefit many more young people going forward.
Growing up in nearby Rancho Cucamonga, Kaleb and his older sister had a typical normal, healthy childhood, watched over by their father, Brian, an elevator mechanic, and mom Tracy, a restaurant manager.
“Normal,” however, changed when COVID-19 struck in early 2020. With everything shut down, Kaleb started high school at home, separated from friends and teachers.
When schools reopened in time for his junior year, Kaleb was determined to make up for lost time. He’d never played football before. But now, why not try?
“He started playing after the pandemic,” said his dad, Brian. “He began in his junior year. He had a blast, and he was getting really good at it.”
But by November 2022, Kaleb was playing hurt. “It caught me off guard,” he recalls. His right leg had begun to swell “uncontrollably” and cause pain he rates at a “6 or 7” out of 10. But he kept playing. “It kept swelling more and more, and it never went away,” he said.
Everyone thought Kaleb had injured himself, so the family consulted an orthopedist. A magnetic resonance imaging (MRI) scan showed nothing torn or broken, but fluid had accumulated near his knee. That’s when the orthopedist startled the family, telling them to take Kaleb to a rheumatologist —.and an oncologist.
When Brian heard “oncologist,” he shuddered.
“My little brother died of a brain tumor,” Brian recalled. “Our dad died of colorectal cancer that spread to his liver.”
The orthopedist reassured them. Kaleb almost certainly did not have cancer, he said. “But he said ‘oncologists are better with bones,’” added Brian.
The doctor had a point.
“We do see benign tumors here,” said Janet Yoon, M.D., medical director of City of Hope’s Pediatric Musculoskeletal Tumor Program. “We’re familiar with them, and we can often use some targeted therapies and even some chemotherapies to treat them.”
A Diffuse Tenosynovial Giant Cell Tumor Diagnosis
At City of Hope, Kaleb was diagnosed with a diffuse tenosynovial giant cell tumor (TGCT), a benign, slow-growing and very rare (four cases per million) condition that more commonly strikes adults in their twenties and thirties. Diffuse TGCT develops around a large joint — in Kaleb’s case, his knee — often forming in the synovium, a thin layer of tissue that covers the inner surface of the joint.
Because they’re benign, there is no danger of TGCTs spreading to other areas or becoming life-threatening. However, left untreated, these tumors can keep growing and eventually damage the joint, cause disability, and in rare cases even require amputation.
Typically, this condition is treated by surgically removing the tumor. Recovery can be long and slow, and there’s a 50% chance of recurrence.
Kaleb didn’t like the sound of that. Having just begun to enjoy high school life and excel on the football field, he was loath to abruptly cut it short.
“Here was this high school kid who wanted to keep being a high school kid, to be around his buddies,” said Yoon.
But there was another possibility. And thanks in large part to the unique collaborative atmosphere at City of Hope, it became a very good possibility.
Hope From a New Drug Therapy
It is believed that TGCTs form because of a genetic “translocation”: a disruptive rearrangement in a particular chromosome. It’s not clear why this happens. Cells containing this translocation overproduce a protein called colony stimulating factor-1, or CSF-1. This protein binds to cells that have a CSF-1 receptor. These cells make up the bulk of TSGTs.
In theory, blocking the action of CSF-1 should stop TGCTs from growing and maybe even eliminate them. Theory became reality in 2019 when the Food and Drug Administration (FDA) approved the first CSF-1 inhibitor, a targeted therapy drug called pexidartinib (commercial name: Turalio). In clinical trials, pexidartinib produced a positive response in 50% of cases; in 18% of them, the tumor disappeared completely.
But the FDA approval was for adults. The drug was still untested in children. Kaleb was 16 at the time — true, a big, strapping 16, but technically still a child. Giving him this new drug would be breaking new ground. Did Kaleb and his family want to go that route?
“We were concerned we might be just kicking the can down the road,” said Brian. If the drug didn’t work, Kaleb would need surgery in the end. But if it did succeed, Kaleb might avoid surgery altogether, stay in school and keep playing sports without interruption. “We left it entirely up to him. And he wanted to try.”
Yoon says putting off surgery wasn’t dangerous. This was not a malignancy that had to be arrested immediately. “It is very slow-growing,” she emphasized, adding, “I would never, ever do this with a malignant tumor.”
Nevertheless, there was a learning curve involved. Before joining City of Hope, Yoon had spent much of her career at children’s hospitals. TGCTs are very rare in kids, and Yoon had never treated one before. She needed guidance on how to proceed with pexidartinib, as well as official certification that would allow her to do so.
Fortunately, she says, help was right there on campus. “That was one of the big draws for me to come here,” she said.
Yoon consulted with a colleague in the Division of Sarcoma Medical Oncology, Department of Medical Oncology & Therapeutics Research, who had experience treating adults with pexidartinib. He helped Yoon get up to speed and become an FDA-certified prescriber for the drug, which includes an agreement to monitor for liver damage, a possible side effect.
At the same time, they helped the Warmans handle a lengthy appeals process with their insurance companies, who ultimately agreed to cover pexidartinib for Kaleb.
All this teamwork on their behalf impressed the family, who never expected a cancer center to do so much for a patient who didn’t have cancer.
“I’ve never experienced such a place,” said Brian. “It’s an embarrassment of riches, everything they have there. I admit, I felt a little guilty about it.”
Helping Future Patients
It goes both ways, said Yoon. Her experience with Kaleb is already helping her treat other patients.
“I have a new patient, younger than Kaleb,” she said. “Now I know exactly how to enroll him for this drug, and I’m able to share with his parents the positive results I’m getting with Kaleb, and that’s very helpful. It can be hard to sell parents on using an adult drug on their kids.” She can’t emphasize strongly enough how important this is. “Pediatric patients need access to drugs like this.”
Kaleb’s results, says Yoon, have been “phenomenal.”
He started on pexidartinib in June 2023. By August, the pain and swelling had vanished. After six months, the tumor was gone. Side effects were minimal. Some itching at first, and a rash. He would bruise easily. No liver damage, and he’s switched to a low-fat diet to keep it that way. And yes, his strawberry blonde hair got considerably lighter — one unusual side effect of the medication. He’s OK with that. Now he’s a football jock with a surfer dude vibe.
Kaleb will stay on the drug for a full year, getting periodic scans to check for recurrence as well as tests to monitor his liver. So far, so good. His first two MRIs showed no evidence of disease.
He’s delighted to have avoided surgery, and he’s looking forward to continuing to be able “to walk normally 30 years from now.”
Dad says coming to City of Hope made all the difference.
“Consider the power of a moment of pause,” he advises other parents. “Take a moment to dig deeper. I could have been a mess. But these people work tirelessly. They go to all lengths for you, and they’re good at it. I looked around. I saw how they’re on the cutting edge, how they’re out in front of things.
“It’s been a fantastic experience.”
At City of Hope Children’s Cancer Center, our expert providers are dedicated to delivering world-class, personalized care for children, adolescents and young adults. Each patient is cared for by a multidisciplinary team of oncologists, hematologists, surgeons, radiation therapists, pathologists and supportive care staff, including child life specialists. Our team has access to leading-edge treatments, including our world-renowned stem cell and bone marrow transplantation programs and the latest clinical trials. Our specialists work together to develop a unique, targeted treatment plan for every patient while providing family support. Continuing care into adulthood for survivors, our Childhood, Adolescent and Young Adult Survivorship Program provides specialized follow-up care for patients who have completed treatment for cancer or a similar illness that was diagnosed before 40 years of age.