Seattle Children’s Study Finds ‘Home Run’ Survival Improvement for Kids With Most Common Form of Leukemia, Changing Care

Dec. 9, 2024 – On Halloween 2023, 4-year-old Rowan Synnott was excited to go trick-or-treating with his big brother, Colin, in Seattle’s Ballard neighborhood. Dressed as Spider-Man, one of his favorite superheroes, Rowan looked forward to an evening of candy and jack-o’-lanterns.

But Rowan’s parents’ “spidey senses” began tingling as the night wore on. Their normally active preschooler was struggling to climb stairs as they went door to door. He later spiked a fever, so mom Erin Rooney took him to the doctor the next day, who assured her the bug would pass quickly.

It didn’t. The fever hung on and climbed, and Rowan’s lymph nodes began to swell. On the fifth night, his parents grew concerned enough to trek to Seattle Children’s Emergency Department at 3 a.m. for some answers.

Erin remembers her shock when the doctors told her Rowan’s symptoms weren’t from a virus, but rather B-cell acute lymphoblastic leukemia (B-ALL).

“It was like the wind was knocked out of me. I could barely speak,” Erin said. “I'm a very action-oriented person, so once my breath returned, I just remember being like, well, what do I do next? How is Andrew [Rowan’s father, who was taking Colin to school] going to handle this? How do I tell Rowan?”

Rowan’s doctors assured Erin that the blood cancer — the most common form of childhood cancer — was very treatable, and though she was reeling, she knew they were in the right place.

“They took us up from the ER to the oncology floor, and it was very swift and impressive, but also overwhelming,” she recalls. “They were just so organized.”

Also, a comforting coincidence: Rowan’s 41-year-old uncle, Michael, had B-ALL as a kid and was living proof such a diagnosis was survivable.

A Leukemia Clinical Study Option

Rowan began induction chemotherapy through Children’s Cancer and Blood Disorders Center and tolerated the treatment well. He was also offered a spot in a clinical study at Children’s to determine whether adding blinatumomab, an immunotherapy medicine, in addition to standard chemotherapy as part of a treatment regimen, would improve B-ALL’s already high survival rates.

“With many childhood cancers, especially those that are rarer, there isn't funding for research. So it was nice to hear right when he was diagnosed that there were clinical trials running and maybe an option for Rowan to be part of one,” Erin said. “Just knowing that clinical research was being done and his doctors were involved was encouraging.

“It was a lot to consider, but one of the things that tipped us toward participating is we can't necessarily give a ton of money, but what we can give is our time and Rowan as a research participant to help advance things forward, whether it be for him directly benefiting or for other kids. I think that took away any of the scary. I was like, let's just lean into science,” she said.

“Not only was blinatumomab showing a signal of efficacy, it was really a home run. Results showed a stunning improvement in the rate of three-year disease-free survival of patients from around 87% to around 96%.”

– Dr. Rachel Rau

By being a part of the AALL1731 study, Rowan joined 4,263 patients with B-ALL enrolled at 228 sites across the world. The study is co-led by one of Rowan’s physicians, Rachel Rau, MD, a pediatric hematologist-oncologist at Seattle Children’s with a lab-based research program in the Ben Towne Center for Childhood Cancer and Blood Disorders Research at Seattle Children’s Research Institute.

The research study, which began in July 2019, is coordinated by the Children’s Oncology Group (COG), the world’s largest organization devoted exclusively to childhood and adolescent cancer research. It unites over 10,000 experts in childhood cancer at more than 200 children’s hospitals — including Seattle Children’s — as well as universities and cancer centers across North America, Australia, New Zealand and Saudi Arabia. The consortium is currently led by Doug Hawkins, MD, a senior hematologist-oncologist at Children’s.

Cancer Study Results ‘Beyond Anyone’s Expectations’

Dr. Rau presented findings from the AALL1731 study at the American Society of Hematology (ASH) Annual Meeting on Dec. 8 that showed adding blinatumomab to standard-intensity chemotherapy significantly improved three-year disease-free survival in newly diagnosed children with B-ALL. Researchers from Seattle Children’s Research Institute also contributed to 15 other scientific abstracts being presented at the ASH meeting. The AALL1731 study findings were published in The New England Journal of Medicine.

Patients in the study who received blinatumomab were 61% less likely to relapse (the cancer comes back after treatment) than those in the trial who did not receive the drug, demonstrating a major breakthrough and a potential new treatment standard for children diagnosed with the condition.

“The results show something striking: Not only was blinatumomab showing a signal of efficacy, it was really a home run,” said Dr. Rau, co-first author of the findings. “Results showed a stunning improvement in the rate of three-year disease-free survival of patients from around 87% to around 96%. It was beyond anyone’s expectations.”

Though children with newly diagnosed, standard risk B-ALL have high survival rates when treated with standard chemotherapy, some patients relapse and die. Relapsed ALL is a leading cause of pediatric cancer mortality. About half of all relapses occur in patients originally diagnosed withstandard risk B-ALL. This trial was the first to use blinatumomab for newly diagnosed pediatric patients with this condition. The drug was shown to be safe and effective in previous studies of relapsed patients.

All of the study patients — whose average age was 4.3 years old — initially received standard-intensity induction chemotherapy. After induction chemotherapy, they were assigned to one of three relapse risk categories, based on several biomarkers. Those classified as standard risk-favorable were assigned to the chemotherapy-alone group. The remaining 1,440 patients deemed standard risk-average or -high were randomized (assigned by chance) to either receive chemotherapy alone or chemotherapy plus two 28-day cycles of blinatumomab. Rowan was randomized to the latter group.

A Backpack of Immunotherapy

Blinatumomab is a type of immunotherapy drug called a bispecific T-cell engager. It works by bringing healthy T cells (immune cells that help kill cancer cells) and leukemia cells close together so the T cells can more effectively kill the leukemia cells. It does this by binding to a protein called CD3 on healthy T cells and a protein called CD19 on B cells (immune cells that are cancerous in B-ALL).

Because blinatumomab needs to be continuously delivered to the body, Rowan wore a backpack with the medicine and an IV pump, which connected to his chemo port, a small device implanted under the skin in his chest to deliver medicine to a large vein. It allows healthcare providers to draw blood and give treatments without a needle stick. For two one-month blinatumomab courses, Rowan returned to the hospital twice a week for a new bag of medicine.

Blinatumomab was well tolerated by most of the study participants. Rowan’s mom said her son had flu-like symptoms for the first two days of taking it. “But then, like magic, at 48 hours he perked right up and just had an amazing month. If anything, he felt too good,” said Erin of his energetic antics. “He had no inkling there was a needle sticking into him. He’d forget about the backpack. I picked him up one day from preschool and he's doing army-style rolls outside on the playground. He’d start wrestling with his brother and ride his balance bike like a maniac. Rowan was definitely back to fighting form!”

After completion of study treatment, patients were followed up every four weeks until their bloodwork indicated they were in remission (had no signs or symptoms) from B-ALL, then every three months for the first two years. Their health is checked in increasingly longer intervals in years three through five.

When an interim analysis of the study data in June 2024 after a median follow-up of 2.5 years definitively established that adding blinatumomab to chemotherapy significantly improves disease-free survival, the study’s data safety and monitoring committee recommended early termination of randomization. The trial was closed to accrual as the researchers concluded that most B-ALL patients would benefit from standard chemotherapy plus blinatumomab. The drug is now part of the standard approach to treating most pediatric B-ALL patients.

The researchers will continue following the health of the children in the study and plan to additionally study whether it’s possible to replace some of the more toxic chemotherapy with blinatumomab and other immune-based therapies with less toxic side effects, which would change the treatment landscape for all kids with B-ALL.

Amgen, the drug’s manufacturer, is working to make improvements in how the drug is delivered and aims to find a less burdensome way of giving the medicine to patients than a continuous infusion.

The Power of Patients and Collaboration

“We have so much gratitude for the patients who participated in this clinical trial,” said the study’s co-corresponding and senior author Mignon Loh, MD, Seattle Children’s head of the Division of Pediatric Hematology, Oncology, Bone Marrow Transplant and Cellular Therapy, overseeing the Cancer and Blood Disorders Center, and director of the Ben Towne Center for Childhood Cancer and Blood Disorders Research at Seattle Children’s Research Institute. Dr. Loh previously led the COG ALL Committee and the development of the AALL1731 study. 

Dr. Loh said being part of COG enables researchers to draw definitive conclusions from clinical trials. “Participation in COG allows us to access impactful trials that are able to detect significant differences in outcome,” she said. “When we ask a question about a different kind of therapy, these clinical trials can have a major impact on these otherwise uncommon cancers.”

The study was supported by grants from the National Institutes of Health’s National Cancer Institute and from the St. Baldrick’s Foundation.

— Colleen Steelquist

Further reading

• Seattle Children’s Eradicates Seeley’s High-Risk Leukemia
• PedAL Effort Offers Hope for Hard-To-Treat Cancer
• Less Toxic Cancer Therapies for Healthier Lives