In Landmark Study, Immunotherapy Boosts Survival of Advanced Hodgkin Lymphoma
A treatment that rallies the immune system to destroy cancer raised the survival rate for advanced Hodgkin lymphoma patients to a remarkable 92 percent, suggesting a new standard therapy for the disease. The New England Journal of Medicine published the innovative clinical trial results this week, along with an editorial that supports the new treatment for all stages of this disease.
Young people are most at risk to get Hodgkin lymphoma, an uncommon blood and immune system cancer that falls within the general category of lymphomas. With this new immunotherapy approach, scientists believe they found a way to reduce long-term side effects of treatment—including second cancers later in life and heart and lung conditions—as immunotherapy appears to be less toxic. The late side effects are most often associated with radiation treatment.
“We will see many less breast cancers 20 to 30 years later in this group of patients, less infertility, less heart disease,” said Wilmot Cancer Institute Director Jonathan Friedberg, MD, MMSc, at the University of Rochester Medical Center, who led the study and is the corresponding author.
Standard care for Hodgkin lymphoma, which typically involves chemotherapy and often radiation therapy in the youngest patients, already has a cure rate of higher than 80 percent.
“But the 20 percent who are not cured have a long road ahead,” Friedberg said. “The goal of this study was to improve the cure rate while also minimizing side effects and long-term toxicities—and that’s what makes this an unprecedented clinical trial.”
Speaking to the trend of using drugs that help the immune system fight cancer, Friedberg said: “We are in the midst of an immunotherapy revolution,” and as an example cited former President Jimmy Carter, who recently celebrated his 100th birthday. Immunotherapy for melanoma has extended Carter’s life after the deadly skin cancer spread to his brain a decade ago.
Details of a Trailblazing Clinical Trial for Hodgkin Lymphoma
Friedberg is chair of the lymphoma committee at the SWOG Cancer Research Network. A large team at SWOG conducted the research as part of the National Cancer Institute (NCI)-funded National Clinical Trials Network.
“This trial is an example of the power of the cooperative group system,” Friedberg said. “It would not have been possible without outstanding collaborations among literally dozens of colleagues across the U.S. and Canada.”
Key points from the trial, known as S1826:
- Nearly 1,000 patients enrolled in the randomized, phase 3 study at hundreds of cancer clinics and academic institutions in North America through the SWOG network. The median age of patients with Hodgkin lymphoma in the study is 30.
- Half of the individuals received the latest standard therapy: chemotherapy and a drug called brentuximab vedotin. The other half received chemotherapy plus an immunotherapy, nivolumab, which targets a genetic alteration common in Hodgkin lymphoma.
- After two years of follow-up, 92 percent of the people in the immunotherapy group had not only survived but saw no progression of disease, versus 83 percent in the standard care group.
- Researchers designed the study to be highly inclusive. One-third of participants were pediatric patients as young as age 12; about 10 percent were older than 60; and 25 percent were from underrepresented groups, including Black individuals and people who identify as Latino.
- Historically, children with Hodgkin lymphoma have received radiation therapy along with chemotherapy. That treatment, although successful at killing cancer, would often result in significant side effects with life-long implications. In this trial, researchers chose not to not use radiation therapy to minimize those problems and saw fewer side effects and adverse events among the patients who received the immunotherapy.
- The trial took an exceptional approach to combine young and older patients into one study, giving them the exact same treatments. Harmonizing treatments across ages is now serving as a model for other planned studies for adolescents and young adults with cancer, Friedberg said, and it will allow physicians to rapidly introduce novel cancer treatments into the younger population.
- Researchers are continuing to follow the individuals in this study. They are analyzing correlative blood samples and collecting patient evaluations that asks them to describe conditions such as depression and anxiety related to their cancer, fertility issues, and their ability to work and move forward with life.
Friedberg called out the contributions of the study’s first author Alex Herrera, M.D., chief of the division of lymphoma at City of Hope, a large cancer research and treatment center based in Los Angeles; senior biostatistician Michael LeBlanc, PhD, and Hongli Li, MS, both at the Fred Hutch Cancer Center in Seattle; and Kara Kelly, MD, pediatric oncologist at Roswell Park Comprehensive Cancer Center and Sharon Castellino, MD, MSc, pediatric oncologist at Winship Cancer Institute of Emory University, who oversaw accrual through the Children’s Oncology Group, the world’s largest organization devoted to childhood and adolescent cancer research.
Their preliminary trial data was so strong that the NCI ordered the study to stop early, to facilitate a faster review by the U.S. Food and Drug Administration. The American Society of Clinical Oncology (ASCO) highlighted those results in 2023, which at that point had one year of follow-up data. The results published in the New England Journal of Medicine includes two years of patient follow-up and confirms the positive initial findings.
The FDA will determine whether nivolumab should become standard treatment for stage 3 or 4 Hodgkin lymphoma. Because nivolumab is already approved for other indications and is less expensive than some other Hodgkin lymphoma treatments, Friedberg anticipates that it will quickly emerge as part of regular care. The journal’s editorial noted that the immunotherapy (nivolumab) regimen is “easy to deliver, is associated with modest toxic effects, and is highly effective.”
The NCI funded the research. Bristol-Myers Squibb, which produces nivolumab, supported the study in a cooperative agreement with the NCI.