CREDIT: ADOBE STOCK
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COG research leads to game-changing improvements for pediatric Hodgkin lymphoma treatmentWhen scientists tested a new, more targeted treatment for pediatric Hodgkin lymphoma, they hoped it might work as well as the standard treatments. The results revealed something they never expected.
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Hodgkin lymphoma has long been one of the most curable pediatric cancers. Even in the early 1970s, around 80 percent of children with Hodgkin lymphoma survived five years after treatment, compared to only 10-20 percent of children with the most common childhood cancer at the time, acute lymphoblastic leukemia. Thanks to years of research, people under 20 years old diagnosed with Hodgkin lymphoma now have a 98 percent survival rate. 1
But when Sharon Castellino, M.D., was pursuing her masters in Health Outcomes and Health Services Research, she wanted to look deeper into these statistics. She knew that the first five years of survival after treatment is a key milestone. But how do children who survived Hodgkin Lymphoma do 10, 15 or 20 years later?
“We realized that even though we’d cured their Hodgkin lymphoma, the chemotherapy and radiation we used to treat it led to serious consequences: many patients experienced thyroid cancer, breast cancer, premature heart disease and other health problems starting around 15 years after initial treatment,” said Dr. Castellino, who is the current chair of the Children’s Oncology Group (COG) Hodgkin’s Lymphoma Committee and Director of the Leukemia and Lymphoma Program at the Aflac Cancer & Blood Disorders Center of Children's Healthcare of Atlanta and Professor of Pediatrics at Emory University.
Those findings sparked a new mission for Dr. Castellino: Identify treatments that could cure Hodgkin lymphoma without causing serious health problems years later. The key would be finding more targeted treatments that could destroy cancer cells and reduce and tailor the need for significant radiation.
Then in 2022, a huge breakthrough was made when the FDA approved a new medicine called brentuximab vedotin for use in children, fueled by a Children’s Oncology Group (COG) clinical trial.
“This is the first indication we’ve seen where highly targeted medicines could allow us to only use radiation in very specific cases, or not use it at all as a frontline treatment,” Dr. Castellino said.
But when Sharon Castellino, M.D., was pursuing her masters in Health Outcomes and Health Services Research, she wanted to look deeper into these statistics. She knew that the first five years of survival after treatment is a key milestone. But how do children who survived Hodgkin Lymphoma do 10, 15 or 20 years later?
“We realized that even though we’d cured their Hodgkin lymphoma, the chemotherapy and radiation we used to treat it led to serious consequences: many patients experienced thyroid cancer, breast cancer, premature heart disease and other health problems starting around 15 years after initial treatment,” said Dr. Castellino, who is the current chair of the Children’s Oncology Group (COG) Hodgkin’s Lymphoma Committee and Director of the Leukemia and Lymphoma Program at the Aflac Cancer & Blood Disorders Center of Children's Healthcare of Atlanta and Professor of Pediatrics at Emory University.
Those findings sparked a new mission for Dr. Castellino: Identify treatments that could cure Hodgkin lymphoma without causing serious health problems years later. The key would be finding more targeted treatments that could destroy cancer cells and reduce and tailor the need for significant radiation.
Then in 2022, a huge breakthrough was made when the FDA approved a new medicine called brentuximab vedotin for use in children, fueled by a Children’s Oncology Group (COG) clinical trial.
“This is the first indication we’ve seen where highly targeted medicines could allow us to only use radiation in very specific cases, or not use it at all as a frontline treatment,” Dr. Castellino said.
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How advances in adult medicine fuel progress for pediatrics
Brentuximab vedotin first caught Dr. Castellino’s eye around the time she published her findings about the late effects of Hodgkin lymphoma treatment in 2011. This medicine was being tested in adults with relapsed Hodgkin lymphoma (when cancer comes back after initial treatment). It worked so well that researchers soon started a new trial testing it as a frontline treatment in adults. Dr. Castellino was particularly interested in this treatment for children because it was so targeted. “It targets a protein called CD30, which seems to be unique to certain types of lymphoma. So, if we can target just that one protein, we might be able to take out just the cancer cells without harming healthy cells,” Dr. Castellino said. She was well aware that starting clinical trials for new medicines in children can be a long and slow process — understandably, because trial investigators want at least some concrete data on a medicine and its side effects before using it in children. The effectiveness of brentuximab vedotin in adults paved the way for a trial in kids. And in 2015, Dr. Castellino launched a COG trial that would test this medicine in children, teens and adults up to age 21 with high-risk classic Hodgkin lymphoma. A clinical trial and a difficult choice Dr. Castellino and doctors at COG centers across the country were soon giving patients and their families a choice: the tried and true treatment, or a new, and possibly better treatment through a clinical trial. |
"The progress Dr. Castellino is making for Hodgkin lymphoma patients is important, as we all strive to give childhood cancer survivors longer and healthier lives. The COG, like St. Baldrick’s, is committed to advancing treatments for the whole spectrum of pediatric cancers — types that are almost always fatal, to Hodgkin lymphoma and others, where so much progress has already been made. Every child’s life is worth saving, and until every child survives and thrives, the need for research is there – no matter what the diagnosis." Becky Chapman Weaver Chief Mission Officer St Baldrick's Foundation |
“These were difficult conversations to have and hard choices for families, because on one hand, we had a treatment that was known to be curative, but also known to cause significant long-term side effects. On the other hand, we had a treatment that was very promising in adults, but we did not know how it would work in children,” Dr. Castellino said.
Some families chose the tried and true treatment. But many families opted to become part of the next generation of medical breakthroughs and joined the trial.
Thanks to the broad reach of COG, families across the country participated, including many families from groups that are often underrepresented in scientific research.
“The geographic diversity of COG-affiliated treatment centers spans patients in terms of race, ethnicity and geographic location in the U.S. and Canada,” Dr. Castellino said. “This enables us to conduct trials with a lens on equity. We know that new medicines may work variably in different populations, so having a diverse group of patients in our trial helps collect the best data. More importantly, it enables us to get these medicines to more children who need them and have a clear understanding of how they work.”
Doctors and patient families celebrate surprising results
The final results were something Dr. Castellino never expected.
“We thought brentuximab vedotin had a good chance of working. Our best hope was that it would work about as well as the existing treatment or a little better,” Dr. Castellino said. “But the magnitude of the difference of the treatment was unexpected.”
The new medicine worked significantly better than the standard of care treatment: Patients who received brentuximab vedotin were 10 percent less likely to relapse within 3.5 years of their treatment. With the standard treatment about 18 percent of kids relapse. But of those who received brentuximab vedotin, only about 8 percent had relapsed 3.5 years after treatment.
“These were very exciting results,” Dr. Castellino said. “Our hope is that as we continue to follow these patients, we won’t see as many late impacts on health like heart disease and secondary cancers as a significantly lower portion of patients required radiation treatment which has been strongly associated with these late effects.”
This new therapy is now a frontline treatment for pediatric Hodgkin lymphoma. This significant advance is a testament to the entire pediatric cancer community — the physician-scientists who dedicate their time, the donors who support trials like these and the families who say yes to the next frontiers of medicine in hopes for better futures for kids. And standing beside all of the research and care, are donors like the St. Baldrick’s Foundation who provided significant support for Dr. Castellino’s study.
“The current reality is that a cure for cancer can lead to a chronic disease for many patients,” Dr. Castellino said. “We hope to change that. We are now in an era of rapidly evolving science and novel targeted agents against cancer. COG has played a leading role and really put the child and their long-term needs at the heart of that care.”
1 Source: https://www.cancer.gov/types/lymphoma/hp/child-hodgkin-treatment-pdq