Landmark Clinical Trial Shows Value of Immunotherapy for Hodgkin Lymphoma

Hodgkin Lymphoma: Hodgkin LymphomaA new study published in the New England Journal of Medicine (NEJM) demonstrates the value of adding the immunotherapy drug nivolumab to standard chemotherapy for patients with Hodgkin lymphoma. The large trial of nearly 1,000 patients, funded by the NCI, was a collaboration of over 200 centers in the U.S. and Canada (2024; https://doi.org/10.1056/NEJMoa2405888). The study participants were newly diagnosed patients with Stage III or IV Hodgkin lymphoma. The trial randomized patients between two groups: standard AVD (adriamycin, vinblastine, and dacarbazine) chemotherapy with the targeted agent brentuximab vedotin or the same chemotherapy regimen with nivolumab. The endpoint was progression-free survival. After 2 years of follow-up, patients treated in the nivolumab group showed a 92 percent progression-free survival rate compared to the other group that had an 83 percent progression-free survival rate. Those in the nivolumab group had fewer side effects and, importantly, reduced use of radiation therapy, which can lead to serious treatment side effects later in life. “This was an exciting, really trail-blazing study for several reasons,” said study co-author and the article's corresponding author Jonathan W. Friedberg, MD, MMSc, Director of the Wilmot Cancer Institute at the University of Rochester Medical Center. Friedberg, who serves as Editor-in-Chief of the Journal of Clinical Oncology and Chair of the Lymphoma Committee for the SWOG Cancer Research Institute, added, “We're curing substantially more patients with this regimen.” He noted the study results represent the fact that, in oncology, “we're in the midst of an immunotherapy revolution.” As an example, he cited former President Jimmy Carter, who recently turned 100 and whose life has been extended by immunotherapy for melanoma that spread to his brain. Friedberg noted that, because of a specific chromosomal issue, Hodgkin lymphoma cells appear to be “exquisitely sensitive” to nivolumab. Speaking during a news briefing, Friedberg noted that, in the 1960s, Hodgkin lymphoma “was a uniform death sentence for patients” and its treatment is a success story. However, although most patients with Hodgkin lymphoma are cured, there are “still about 20-25 percent of patients who are not cured, and those patients need to go on and get significant toxic therapy.” Because the disease disproportionately affects younger patients, they may have 50 or more years to live after treatment. Thus, he said avoiding radiation—which the study was designed to do—can help prevent side effects and secondary cancers in treated patients later in life. “We will see fewer breast cancers 20-30 years later in this group of patients, less infertility, and less heart disease,” he predicted. In this study, only six patients received radiation therapy. Friedberg said the highest percentage of patients who develop secondary cancers are those who have radiation, so cutting out radiation reduces that risk. Also, he noted that brentuximab generally produced higher levels of side effects than did nivolumab. The one side effect that was higher in the nivolumab group was neutropenia. Friedberg said he is optimistic that the nivolumab regimen will become a standard of care for Hodgkin lymphoma because all of the drugs are approved, and the nivolumab regimen is less expensive and less toxic. The median age of patients diagnosed with Hodgkin lymphoma is about 30, noted Friedberg, and lower rates of frequently seen serious radiation side effects can be expected in the nivolumab group years after treatment. Follow-up to this study will also include patient-reported outcomes (PROs). He said the study was unusual because it included children; one-third of patients were enrolled by pediatricians and some of the participants were as young as 12. He said it was also unusual in its diverse representation of U.S. population groups. For example, 12 percent of study participants were Black and 13 percent were of Latino origin, which makes the results more widely applicable. Friedberg stressed the need to use the best and least toxic treatment regimen available, especially for younger patients with Hodgkin lymphoma. The goal is to achieve sustained remission while mitigating the occurrence of long-term adverse events. He noted that he treats college students and graduate students, and this cancer diagnosis presents a real challenge for them. “It really interrupts life for 6-12 months,” Friedberg said. So, the more the treatment can be refined and the sooner these younger patients can get back to normalcy in pursuing their schooling or their careers, the better, he said. Hodgkin lymphoma survivor Jenna Cottrell agreed with Friedberg. Cottrell is an ABC sports broadcaster in Rochester, NY, who was diagnosed in 2017 at the age of 25. Now in remission, she was not part of this trial, but spoke about what this cancer diagnosis means to a young adult. “I've been in remission since 2017, but the physical toll that it did take on my body both mentally and emotionally was a challenging journey,” she said, describing feeling extremely fatigued and weak. “When you're 25, you're not used to feeling not invincible.” Cottrell added, “It is very stressful. I feel I am acutely aware of my body now and how it responds to things.” She hailed the results of the trial as good news for young adults in the future who will receive the diagnosis she did. Cottrell said knowing the risk of secondary cancers might be reduced may help future young people with this diagnosis feel they can be less vigilant and that “is important to hear.” “I just can't help but feel so positive for future patients,” she added. In addition to showing value for younger patients, Friedberg said the nivolumab regimen also holds promise in meeting an unmet need for patients over the age of 60. In this study, 10 percent of patients were over age 60. He noted that this group has been largely overlooked and underserved in previous clinical trials. Friedberg said next steps in this research include long-term follow-up of the study population, including blood tests, conducting further correlative studies to identify patient subsets that may benefit differentially from the two treatment approaches studied, evaluating collected PROs (such as whether women desiring to become pregnant were able to do so), and tracking the trial participants to assess the impact of secondary cancers and other long-term effects. Peggy Eastman is a contributing writer.

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