Boosting new options for young people with advanced Hodgkin lymphoma

An historic and groundbreaking clinical trial, which for the first time in the modern era included both adolescents and adults with advanced Hodgkin Lymphoma (HL), showed that 94% of the patients treated with an experimental immunotherapy plus chemotherapy were cancer-free or had no progression of disease after one year.

The results are likely to change standard treatment for this type of cancer, said University of Rochester Wilmot Cancer Institute Director Jonathan Friedberg, M.D., M.M.Sc. He is senior investigator of the study and chair of the lymphoma committee at the SWOG Cancer Research Network, which designed the S1836 trial as a part of the National Cancer Institute-funded National Clinical Trials Network.

"We hypothesized that the newer treatment would turn out to be most beneficial for patients," Friedberg said, "but the magnitude of the benefit exceeded our expectations."

The American Society of Clinical Oncology (ASCO) is to showcase the research at a plenary session on June 4, 2023, because of its high merit and great impact on oncology research. ASCO is the largest meeting of oncologists in the world.

HL is a rare cancer that afflicts mostly young people. The randomized, phase 3 study compared standard treatment with chemotherapy and brentuximab vedotin (brand name: Adcetris) against the immunotherapy, nivolumab (brand name: Opdivo) plus chemotherapy. About 86% of the people in the standard treatment group achieved remission, compared to the 94% who received the newer therapy.

When the strong data came in, the National Cancer Institute (NCI) ordered that the trial be stopped early to facilitate a faster review by the U.S. Food and Drug Administration for ultimate approval of nivolumab-AVD as an initial treatment for stage 3 or 4 HL.

ASCO also featured the research at a June 3 press program, hosted by lead investigator Alex Herrera, M.D., chief, division of lymphoma, at City of Hope, a large cancer research and treatment organization based in Los Angeles.

"The results are remarkable. The combination of nivolumab and chemotherapy is potent and safe in patients with stage 3 or 4 classic Hodgkin lymphoma as an initial treatment," Herrera said. "This is indeed great news for patients with this cancer, as there is another effective and safe option for them."

A nurse becomes a patient

Hodgkin lymphoma impacts the lymphatic and immune systems. Early symptoms can be vague, and sometimes HL is overlooked in otherwise young, healthy people. Symptoms may include fatigue, weight loss, fever, night sweats, and swollen lymph nodes. Patients have a median age of 29.

Hannah Lundgren, 27, was launching her career as a registered nurse in 2020 when she noticed a swollen node in her neck and weight loss.

But she had been working long hours during the COVID-19 pandemic and her doctor wondered if stress and exhaustion could be the culprit. When her symptoms worsened, however, she insisted on imaging tests, blood work, and sought specialty care. After many months without answers, a physician at another local health system sent her to Wilmot at the University of Rochester Medical Center, where she was diagnosed in 2021 with stage 4 HL.

"I was so sick. I was basically a shell of myself, in auto pilot, but still working full-time," Lundgren recalled. "Dr. Friedberg ended up being my oncologist, and he was excited about the clinical trial. The way he explained everything made perfect sense. I knew that even if I was randomized to the standard treatment arm, I was getting good treatment."

It turns out that she was randomly assigned to the immunotherapy group (nivolumab-AVD)—and she noticed after her first treatment that the fatigue suddenly vanished. "It was crazy," she said. "And I also didn't have any more palpable lymph nodes."

Lundgren continued with infusions for six months. On Dec. 7, 2021, she was declared cancer-free.

"I hadn't received good news from a doctor in quite a while," she said.

Lundgren added, "Clinical trials are a great opportunity to redefine what it means to go through cancer treatment. I had this image beforehand of not being able to do things. But life doesn't stop, and I was actually able to work and go on with my life during treatment, which is especially important for a young person."

In fact, she got engaged to be married, enrolled in a nurse practitioner program, traveled to the Adirondack Mountains, and was strong enough to run a half-marathon last October.

After her treatment ended, Friedberg asked her to join him as he gave a lymphoma lecture for UR School of Medicine and Dentistry students. She was so captivated that it led to a major career change from orthopedic trauma nursing to oncology nursing. Lundgren, RN, BSN, now cares for gastrointestinal cancer patients at Wilmot.

"I had something horrible happen to me," Lundgren said, "but now I can make something good out of it."

How researchers boosted remission for Hodgkin lymphoma

The chances of a cure for early-stage Hodgkin lymphoma are 90% to 100%. When the disease has advanced, remission rates drop to about 82%.

Nivolumab is already being used to treat HL that has spread later or relapsed. In this study, it was evaluated as front-line therapy in people who had advanced disease when they were newly diagnosed. The goal was to improve the remission rates in those patients, Friedberg said.

A key part of the study design, he added, was to include pediatric patients ages 12 and older. The standard treatment for them has often included radiation therapy, which carries risks of serious side effects later in life, such as second cancers, thyroid dysfunction, and heart disease.

"By eliminating radiation for children enrolled in this trial, we essentially took away the risks of many toxic late effects," Friedberg said. "But we only have one year of follow-up data for our trial at this point, and we will continue to watch for side effects in the future."

Nearly 1,000 individuals were enrolled in the study between July of 2019 and October of 2022, at more than 200 institutions in North America. The number of Black and Latino patients was aligned with the general population, which was also a goal of researchers.

Data show that thus far, 11 deaths occurred among patients who received standard therapy, compared to four deaths in the immunotherapy group.

Wilmot recruited the second highest number of people with Hodgkin lymphoma to the study, led locally by Wilmot oncologist Carla Casulo, M.D., associate professor of Hematology/Oncology, and an international expert and clinician-researcher for lymphoma.

Hundreds of investigators were involved through SWOG and the NCTN. In addition to the NCI, which is part of the National Institutes of Health, Bristol-Myers Squibb, which produces nivolumab, also supported the research through a cooperative agreement between the company and the NCI.

"This study speaks to the power of these networks and the transformative research that the National Cancer Institute funds," said Friedberg, who is also editor-in-chief of the Journal of Clinical Oncology, the flagship medical journal for cancer.

"Hodgkin lymphoma is not a common disease and the NCTN enabled more than 200 pediatric and adult community providers and academic medical centers to work together," he said. "Because of that, we were able to get data very quickly and directly impact patient care. This was a critical investment in cancer research and treatment."

Provided by University of Rochester Medical Center