Global clinical trial shows improved survival rates for common childhood leukemia

Just days before his fourth birthday, Santiago was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL), the most common cancer among children. He started chemotherapy the next day, and the outlook was promising: Disease-free survival rates for B-ALL are among the highest among pediatric cancers, between 80 and 85 percent. However, limited progress has been made over the past 15 years and B-ALL relapses remain a leading cause of cancer death in children.

Looking to explore all options, Santiago’s parents enrolled him in a Children’s Oncology Group clinical trial led by scientists from the Hospital for Sick Children (SickKids) and Seattle Children’s Hospital. The trial, which included more than two hundred sites in four countries, combined standard chemotherapy with two cycles of blinatumomab, an immunotherapy already used for children with relapsed B-ALL.

The initial results of the study were so promising that the trial ended prematurely and the results were published in the New England Journal of Medicine showing a striking 61% reduction in the risk of B-ALL relapse or death for those who received both chemotherapy and blinatumomab.

“This groundbreaking data showing a significant improvement in disease-free survival is expected to provide considerable clinical benefit to almost all children with newly diagnosed B-ALL,” said study co-leader Dr. Sumit Gupta, an oncologist and associate scientist in the field of children. Health Assessment Science Program at SickKids. “This changes the standard of care for children with B-ALL worldwide.”

Reduce relapses and side effects

Before participating in the trial, Santiago received a combination therapy of steroids and chemotherapy, already personalized based on a genetic analysis of his leukemia cells showing which drugs would be most effective for him.

“We knew treatment was necessary, but the weight gain and loss of independence from steroids was heartbreaking to see,” says Santiago’s mother Beatriz. “The first dose of blinatumomab had its own side effects, but it was nothing compared to his previous treatment and it gave him much more freedom to be a normal child.”

Unlike chemotherapy, immunotherapies like blinatumomab use the body’s immune system to fight cancer by teaching the immune system to target cancer cells. For children like Santiago at average risk of relapse, the study showed that after three years, the disease-free survival rate increased to 97.5 percent, compared to 90 percent with chemotherapy alone. For children at higher risk of relapse, blinatumomab in addition to chemotherapy increased the disease-free survival rate from 85% to more than 94%.

“These results highlight the progress made with blinatumomab in preventing relapses and support its role as an essential addition to current therapeutic strategies,” says study co-leader Dr. Rachel Rau, pediatric hematologist-oncologist. at Seattle Children’s Hospital and associate professor of pediatrics at the University of Washington.

A new era for childhood cancer treatment

The results released today involve 1,440 children from Canada, the United States, Australia and New Zealand, and mark an important milestone in the fight against childhood cancer. As a member of the Children’s Oncology Group, SickKids works with more than 11,000 experts worldwide to advance more than 100 active clinical-translational trials at any given time. Among these active trials, those focusing on children with B-ALL are also suspended to introduce blinatumomab into their study plans.

“This new combination treatment is poised to become the new standard of care for these patients, potentially saving many lives and reducing the fear and health consequences associated with relapse,” says Sumit, who is also an associate professor at the University of Toronto.

“We are now designing the next generation of studies to see if we can safely eliminate some of the chemotherapy that is currently the standard of care, while maintaining these exceptional success rates. It’s an incredibly exciting time to be in this field as we begin to try to decrease the short- and long-term side effects associated with treatment.

Nine months after his first diagnosis, Santiago is excited to finally start school in the new year, trading in his shark backpack for one he picked out before his diagnosis. He will continue to undergo a low-intensity chemotherapy regimen intended to prevent the leukemia from returning, but his family is excited to begin this new chapter together.

“This is Santiago’s journey. My job is to hold his hand and make sure he gets the best care possible,” says Beatriz.