IMAGES COURTESY OF DR. SHARON CASTELLINO
Findings from a landmark clinical trial involving Children’s Oncology Group (COG) helped usher in a new era of treatment for adolescents and adults with advanced classic Hodgkin lymphoma, leading to a new standard of care.
Children’s Oncology Group (COG) is excited to announce that a highly effective immunotherapy called nivolumab, given together with chemotherapy, was approved by the FDA on March 20, 2026, for newly diagnosed Stage III and Stage IV classic Hodgkin lymphoma in adolescents and adults.
Nivolumab’s approval resulted from the S1826 study, a collaboration between COG and the adult cooperative research groups led by Southwest Oncology Group (SWOG), with support from Bristol Meyers Squibb. Dr. Kara Kelly, Chair of the COG Hodgkin Lymphoma Committee at the time of development for S1826, called the simultaneous approval a rare milestone: “Pediatric approvals have historically followed adult approvals by six years, so receiving FDA approval for our patients at the same time as the adult indication is extraordinary. COG enrolled nearly a third of the patients in this study. Trial enrollment finished a year earlier than planned in part because of COG’s contributions. Including nivolumab in the standard of care is going to save lives and meaningfully improve quality of life for young people with advanced Hodgkin lymphoma.'”
On paper, classic Hodgkin lymphoma (sometimes called Hodgkin’s) is a success story, with more than 95% of adolescent patients cured at 5 years from diagnosis. In reality, the picture is less rosy.
- About 20% of patients with advanced-stage or high-risk disease had a poor response to initial conventional chemotherapy and radiation. Of those receiving radiation, aggressive high-dose chemotherapy, and stem cell transplantation, only half were cured. Far too many patients died from their disease.
- Survivors who received aggressive salvage therapies are at risk for complex, deteriorating health conditions for the rest of their lives. Almost 10% of relapse survivors experience premature death from treatment-related causes like secondary cancers, cardiovascular disease, and respiratory disease. Even among patients who never relapse, the risk of long-term complications is higher than in many other pediatric cancer types.
COG is committed to better long-term health outcomes for all Hodgkin’s patients. Better long-term health is achieved with targeted treatment, which kills cancer without damaging healthy cells.
In 2013, COG opened its first Hodgkin lymphoma trial of a targeted agent to study an antibody-drug conjugate called brentuximab vedotin, which was approved for adults in 2017. Adding it to chemotherapy improved progression-free survival in children, but half of the patients still required radiation; the pediatric-specific trial led to FDA approval in 2022.
When the FDA fast-tracked immunotherapy agent nivolumab for review in 2014, COG began studying it for Hodgkin lymphoma. Nivolumab is a checkpoint inhibitor, which works differently from brentuximab vedotin. It attaches to a patient’s T-cells, the immune cells that hunt for pathogens, or “not-me” invaders. With nivolumab attached, the immune system recognizes lymphoma cells as “not-me” and kills them.
Early-phase trial results in COG gave researchers hope that nivolumab could cure adolescent Hodgkin’s with less chemotherapy and potentially eliminate the need for radiation and transplant in first-line treatment.
The results from S1826 were even better than expected in three important ways:
- The group of adolescent patients who received nivolumab together with chemotherapy experienced significantly fewer progressions or relapses within 3 years.
- Patients getting nivolumab with chemotherapy experienced dramatically fewer treatment days and hospitalizations, fewer serious side effects, and improved quality of life during treatment.
- Adding nivolumab to chemotherapy eliminated the need for radiation. Historically, half of patients with advanced-stage disease require radiation to achieve a good response; radiation treatment is historically known to cause long-term health complications.
“It’s a landmark shift in the treatment of Hodgkin lymphoma, where radiation is no longer part of frontline treatment for almost anyone with advanced-stage disease,” said Dr. Sharon Castellino, the COG Chair of S1826 and current Scientific Chair of the COG Hodgkin Lymphoma Committee.
Patients on the nivolumab combination are showing better short-term outcomes, and Dr. Castellino expects those gains to hold long-term. But she emphasizes that long-term follow-up will be essential — nivolumab is a newer agent, and its effects on adolescent survivors over decades are not yet understood.
COG Patient Advocate Emilie Lynch, now a pediatric oncology pharmacist at University of Florida, reflects on the significance of nivolumab’s approval for adolescent patients. “This approval benefits kids — middle school and high school students. At 16, I spent four months in treatment. Each chemo cycle required hospital admission, and the three weeks of radiation involved commuting three hours each day with my mom, which was a burden on our family. As a survivor, I monitor my health closely. I’ve had skin cancer already and am monitored very closely for breast cancer due to radiation. I just had a baby, and I’m very grateful I was able to get pregnant, but health conditions from my treatment made the pregnancy more difficult than expected. Nerve pain and fatigue I hadn’t felt in years came back. I’m hopeful that kids who get this nivolumab regimen will go to school during treatment, be cured quickly, and get back to normal life without worrying about long-term effects.”
Clinical research for Hodgkin lymphoma is ongoing at COG. Following the model that was so effective in S1826, COG’s Hodgkin Lymphoma Committee has embarked on two new collaborations with the adult cooperative research groups to expedite trials benefiting adolescents and adults. COG and Dr. Kelly now lead a trial that studies nivolumab for adolescents and adults with early-stage Hodgkin’s. COG is also co-developing a trial to be led by the ECOG-ACRIN adult cooperative group that will adapt treatment intensity to patients’ risk of relapse.
COG scientists have several additional studies in development, doubling down on a biology-driven approach to better understanding this cancer and Hodgkin’s patients:
- Understanding why nivolumab doesn’t work for some patients.
- Exploring biological differences between adolescents and children under 12 with Hodgkin’s. COG scientists hypothesize the cause of Hodgkin lymphoma is different in patients under 12, which may guide COG toward different treatment options for younger kids.
- Continuing the search for biomarkers that predict relapse risk. COG scientists are studying tiny fragments of tumor DNA in patients’ bloodstream (ctDNA). If ctDNA proves as reliable as PET scans, it would become a less expensive way to personalize therapy with less radiation and to identify patients who are likely to be cured with less treatment.
Public-private partnerships in funding can expedite the pace of discovery in Hodgkin lymphoma. Dr. Castellino, current Chair of COG’s Hodgkin Lymphoma Committee, described the model:
“We really want to reduce toxic therapy while improving cure rates, and philanthropy is moving that work forward now. A federal Gabriella Miller Kids First Grant pays lab scientists to sequence the inherited DNA of 1,700 Hodgkin lymphoma patients. Through Children’s Oncology Group Foundation, the Jeffrey Pride Foundation funds the analysis where we look for underlying immune deficiencies in pediatric Hodgkin’s patients. We have no shortage of ideas, only a shortage of funds. Donations to The Children’s Oncology Group Foundation support our research, and we deeply appreciate the donors who fuel this work for kids.”