Immunotherapy increases survival for advanced Hodgkin lymphoma in clinical trial

A treatment that harnesses the immune system to destroy cancer has increased the survival rate of patients with advanced Hodgkin lymphoma to a remarkable 92%, suggesting a new standard treatment for the disease. THE New England Journal of Medicine published the results of innovative clinical trials.

Young people are at greatest risk for Hodgkin lymphoma, a rare cancer of the blood and immune system that falls under the general category of lymphoma. With this new treatment, scientists believe they have found a way to reduce the long-term side effects of treatment, including second cancers later in life and heart and lung disease.

“We’ll see a lot less breast cancer 20 to 30 years later in this group of patients, less infertility, less heart disease,” said Jonathan Friedberg, MD, MMSc, ​​director of the Wilmot Cancer Institute, of the University of Rochester Medical Center, who led the study. study.

Standard care for Hodgkin lymphoma, which typically involves chemotherapy and often radiation therapy in younger patients, already has a cure rate of over 80%.

“But the 20 percent who are not cured have a long way to go,” Friedberg said. “The goal of this study was to improve the cure rate while minimizing side effects and long-term toxicities, and that is what makes this an unprecedented clinical trial.”

Friedberg is principal investigator and corresponding author of the phase III study and chair of the SWOG Cancer Research Network Lymphoma Committee. A large SWOG team conducted the research as part of the National Clinical Trials Network.

“This trial is an example of the power of the cooperative group system,” Friedberg said. “This would not have been possible without the exceptional collaboration of dozens of colleagues across the United States and Canada.”

It drew contributions from first author Alex Herrera, MD, chief of the lymphoma division at City of Hope, a large cancer research and treatment center based in Los Angeles; senior biostatistician Michael LeBlanc, Ph.D., and Hongli Li, MS, both at 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 study enrollment through Children’s Oncology Group, the world’s largest organization dedicated to childhood and adolescent cancer research.

Key points from the trial, known as S1826:

• Nearly 1,000 patients enrolled in the randomized Phase III trial at hundreds of cancer clinics and academic institutions across the United States through the SWOG network. The median age of Hodgkin lymphoma patients participating in the study is 30 years.
• Half of the patients received the latest standard treatment: chemotherapy and a drug called brentuximab vedotin. The other half also received chemotherapy as well as an immunotherapy, nivolumab, which targets a genetic alteration common in Hodgkin’s lymphoma.
• After two years of follow-up, 92% of patients in the immunotherapy group had survived and had seen no progression of their disease, compared to 83% in the standard care group.
• The researchers designed the study to be highly inclusive. A third of the participants were pediatric patients as young as 12 years old; about 10% were over 60; and 25% were from underrepresented groups.
• Historically, pediatric patients with Hodgkin lymphoma often received radiation therapy along with chemotherapy. This treatment, although successful in killing the cancer, would often cause significant side effects with lifelong implications. In this trial, researchers chose not to use radiation therapy to minimize these problems and found fewer side effects and adverse events in patients who received the immunotherapy.
• The trial took an exceptional approach of combining younger and older patients in a single study, giving them the exact same treatments. Harmonizing treatments across age groups now serves as a model for other planned studies of adolescents and young adults with cancer, Friedberg said, and will allow doctors to quickly introduce new treatments for cancer. cancer in the younger population.

Preliminary data from the trial were so strong that the NCI ordered the study terminated prematurely to facilitate faster review by the U.S. Food and Drug Administration. In 2023, the American Society of Clinical Oncology (ASCO) highlighted these results, which then had one year of follow-up data. The latest study confirmed the initial results.

The FDA will determine whether nivolumab should be added as standard treatment for stage 3 or 4 Hodgkin lymphoma. However, because nivolumab is already approved for other indications, Friedberg anticipates it will quickly become part of treatment guidelines and routine care .