Cause for B-CELLebration: Immunotherapy clinical trial closes two years early with history-making success
Dr. Rachel Rau presents the results of the COG study AALL1731 at the American Society of Hematology (ASH) Annual Meeting and Exposition on December 8, 2024
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Cheers and tears spread across the Children’s Oncology Group (COG) network. Finally, after decades of research, many kids diagnosed with B-cell acute lymphoblastic leukemia (ALL), have a new treatment available to them – one that is highly effective and has more manageable side effects.
A shockwave of joy. That’s how pediatric oncologists Rachel Rau, MD, from Seattle Children’s, and Sumit Gupta, MD, PhD, from SickKids in Toronto, describe the weeks following news that the clinical trial they were leading would be closed two years early thanks to its unprecedented success.
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The trial, AALL1731, aimed to improve survival rates for patients with B-cell acute lymphoblastic leukemia (B-ALL), the most common childhood cancer.
The COG researchers hoped that adding an immunotherapy called blinatumomab to the standard treatment plan for B-ALL patients would lower relapse rates. The answer was a resounding and early yes.
“I'm still trying to wrap my head around being part of something that literally changed the way we treat the most common childhood cancer,” Dr. Rau says.
The decision to close the trial early came from the independent committee that monitored the trial’s progress. After reviewing the study’s initial results, the outcomes were clear: adding blinatumomab to treatment substantially reduced relapse rates.
The COG researchers hoped that adding an immunotherapy called blinatumomab to the standard treatment plan for B-ALL patients would lower relapse rates. The answer was a resounding and early yes.
“I'm still trying to wrap my head around being part of something that literally changed the way we treat the most common childhood cancer,” Dr. Rau says.
The decision to close the trial early came from the independent committee that monitored the trial’s progress. After reviewing the study’s initial results, the outcomes were clear: adding blinatumomab to treatment substantially reduced relapse rates.
The physicians explain that the standard treatment for B-ALL was already highly effective, with about 90% of kids experiencing success after their treatment. But around 10% of kids still relapse and doctors had spent years trying to find a way to lower that number.
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“Putting this immunotherapy at the beginning of treatment increased the three-year disease-free survival rate from 88% to 96%. That’s a huge jump,” Dr. Gupta says, noting that the study results were published in the New England Journal of Medicine.
Changing the course of B-cell ALL treatment overnight Dr. Rau and Dr. Gupta heard the news from David Teachey, MD, with Children’s Hospital of Philadelphia (CHOP), who chairs the ALL committee for COG. He was just as overwhelmed with the monumental results as they were and told them that in addition to closing the trial early, the review committee also recommended blinatumomab become part of standard treatment plans for the majority of B-ALL patients – even those currently being treated who had not been part of the trial. |
Dr. Sumit Gupta
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Dr. Rau says; “We went from running a clinical trial to determining a new standard of care.”
As Dr. Gupta began working with his SickKids colleagues to update their patients' care plans, he realized pediatric oncology teams all over the U.S., Canada, Australia, and New Zealand were doing the same thing.
“I had a moment when I realized physicians at every COG site would be explaining to families that there was now a better drug – and how that would give families additional hope and relief,” Dr. Gupta says.
The first task was sharing news of the trial’s results with the 220 COG member hospitals – and informing them about the upcoming changes to treatment plans. COG sites were committed to overcoming the major financial and logistical challenges involved in getting blinatumomab and giving it to their patients.
As Dr. Gupta began working with his SickKids colleagues to update their patients' care plans, he realized pediatric oncology teams all over the U.S., Canada, Australia, and New Zealand were doing the same thing.
“I had a moment when I realized physicians at every COG site would be explaining to families that there was now a better drug – and how that would give families additional hope and relief,” Dr. Gupta says.
The first task was sharing news of the trial’s results with the 220 COG member hospitals – and informing them about the upcoming changes to treatment plans. COG sites were committed to overcoming the major financial and logistical challenges involved in getting blinatumomab and giving it to their patients.
Dr. Rachel Rau
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In addition, Dr. Rau, Dr. Gupta and COG leaders turned to the pharmaceutical company, Amgen, which makes and supplies blinatumomab. Amgen was equally excited to learn that blinatumomab was so effective. They quickly agreed to make blinatumomab available to patients who participated in the study but didn’t receive the therapy. “The effort it took to get this therapy to thousands of kids is a wonderful testament to how dedicated the pediatric cancer community is, and COG is what has allowed us to create the culture of collaboration,” Dr. Rau says. |
Taking a big step toward more targeted treatments
Blinatumomab works by attaching itself to the CD19 protein, which is present on the surface of virtually all cancerous B-ALL cells. The drug also directs the body’s immune-fighting T cells to seek out CD19 positive B-ALL cells. When the cancer cells and the immune cells get close enough, the T cells attack and destroy the cancer.
“Now, when a child is diagnosed with B-ALL, their treatment plan will include two month-long treatments of blinatumomab between blocks of their standard chemotherapy treatments,” Dr. Rau says.
Having a targeted immunotherapy as part of the standard treatment plan is a victory for B-cell ALL patients, which make up about 85% of all ALL diagnoses.
“Chemotherapies are great at destroying fast-growing cells, but they don’t know the difference between good, healthy, fast-growing cells and fast-growing cancer cells,” Dr. Gupta says. “When I talk to families, I explain that immunotherapies are much smarter versions of chemotherapies because they generally leave most of the healthy cells alone and focus on destroying the cancer cells.”
Blinatumomab works by attaching itself to the CD19 protein, which is present on the surface of virtually all cancerous B-ALL cells. The drug also directs the body’s immune-fighting T cells to seek out CD19 positive B-ALL cells. When the cancer cells and the immune cells get close enough, the T cells attack and destroy the cancer.
“Now, when a child is diagnosed with B-ALL, their treatment plan will include two month-long treatments of blinatumomab between blocks of their standard chemotherapy treatments,” Dr. Rau says.
Having a targeted immunotherapy as part of the standard treatment plan is a victory for B-cell ALL patients, which make up about 85% of all ALL diagnoses.
“Chemotherapies are great at destroying fast-growing cells, but they don’t know the difference between good, healthy, fast-growing cells and fast-growing cancer cells,” Dr. Gupta says. “When I talk to families, I explain that immunotherapies are much smarter versions of chemotherapies because they generally leave most of the healthy cells alone and focus on destroying the cancer cells.”
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Both emphasize that closing the trial doesn’t mean research into blinatumomab is done. Instead, they explain how many new research opportunities will be created because of it.
“Now, we need to study why some patients who receive blinatumomab have more severe side effects than others. We need to understand why there’s still a small group of patients who relapse, even with this therapy,” Dr. Rau says. “Another exciting question is, can blinatumomab replace some parts of traditional chemotherapy rather than just be used in addition to chemotherapy?” Sharing gratitude and making the case for continued advocacy In addition to being grateful to the thousands of people across all 220 COG centers who helped make the study possible, the physicians have specific sentiments for patient families. |
Members of the ALL1731 study team (L to R: Dr. Elizabeth Raetz, Dr. John Kairalla, Dr. Mignon Loh, Dr. Stephen Hunger, Dr. David Teachey, Dr. Sumit Gupta, and Dr. Rachel Rau) meet to celebrate the presentation of the results at the American Society of Hematology meeting in San Diego.
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“We’re grateful for the patient families who participated in this study. We’re also grateful to the families who chose not to participate,” Dr. Rau says. “There are so many difficult decisions and fears that parents face when their child is diagnosed with cancer. We are in awe of the strength you and your children have.”
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Philanthropy helps make the AALL1731 trial a success
A big thank you to the St. Baldrick's Foundation and the Jeffrey Pride Foundation for your support of AALL1731!
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Drs. Rau and Gupta say a huge part of every clinical trial’s success is the collaboration across COG sites between research coordinators, nurses, pharmacists, social workers, and providers, walking families through clinical trial options. The other champions for research, they note, are the patients and families themselves – their dedication as advocates and fundraisers and their hope for all cancer patients has never been greater. |
“We know donor money often comes from families and communities affected by childhood cancer,” Dr. Gupta says. “Philanthropy has become one of the great heroes of pediatric cancer. It’s because of donors, we can keep trying and we will until we have a version of this victory for every child with cancer.”