Could Nivolumab Be A New Benchmark for Advanced Hodgkin Lymphoma Treatment?

  

 

A recent clinical trial suggests that the immunotherapy drug nivolumab (Opdivo), when combined with a standard three-drug chemotherapy (AVD), could be a significant step forward in treating advanced classic Hodgkin lymphoma. The study shows that this combination may not only improve cure rates but also reduce treatment-related side effects, marking a pivotal change in how oncologists approach this disease. 

Key Findings from the Study 

The trial, led by Dr. Jonathan Friedberg of the Wilmot Cancer Institute at the University of Rochester, enrolled nearly 1,000 participants, including adolescents and adults. It demonstrated that nivolumab–AVD significantly outperformed the current standard treatment of brentuximab (Adcetris) combined with AVD.  

Two years after treatment began, approximately 92% of patients in the nivolumab–AVD group had no signs of cancer progression, compared to 83% in the brentuximab–AVD group. Importantly, this improvement came with fewer and less severe side effects. Participants treated with nivolumab–AVD were less likely to experience peripheral neuropathy—a condition associated with brentuximab treatment—and were less likely to discontinue therapy due to these side effects.  

Reduced Reliance on Radiation Therapy  

The study also highlighted a reduced need for radiation therapy, especially in younger patients aged 12–17. Historically, radiation therapy has been key in treatment for Hodgkin lymphoma, particularly for adolescents. However, the long-term risks of radiation—such as secondary cancers and other health issues—have made minimizing its use a priority.  

In the trial, strict criteria limited radiation therapy to only those with residual cancer on post-treatment imaging. As a result, just seven participants required radiation therapy, demonstrating the potential for the nivolumab–AVD regimen to eliminate the need for this additional treatment step.  

Why Nivolumab?  

Nivolumab, a PD-1 immune checkpoint inhibitor, is already used as a second-line treatment for Hodgkin lymphoma that has returned after initial therapy. Its mechanism of action involves reactivating the immune system’s ability to detect and attack cancer cells. Given its success as a second-line treatment, researchers hypothesized that nivolumab might enhance outcomes as part of the initial therapy—a hypothesis strongly supported by this trial.  

Brentuximab, the previous standard, has been a mainstay of first-line treatment for about a decade. While effective, it has notable side effects, including severe nerve pain, gastrointestinal issues, and a high likelihood of treatment discontinuation. By comparison, nivolumab’s safety profile appears more favorable, offering a compelling reason for its adoption in initial treatment protocols.  

The trial enrolled a diverse patient population, with 12% identifying as Black and 13% as Hispanic, making the results broadly applicable across demographic groups. It also included patients aged 12 to over 60.  

For older patients, the nivolumab–AVD regimen showed particular promise. Before, this group has faced poorer outcomes and greater toxicity with brentuximab–AVD. In the study, the two-year progression-free survival rate for patients aged 60 and older reached 88%, which is likely the highest ever reported for this demographic.  

Dr. Friedberg and his colleagues noted that nivolumab–AVD’s reduced toxicity could make it a better option for these patients, as one-third of older participants treated with brentuximab–AVD had to discontinue therapy early due to severe side effects.  

Long-Term Impact and Future Research  

While the trial’s results are promising, longer follow-up is necessary to determine whether these benefits hold over time. Hodgkin lymphoma, particularly in its advanced stages, can sometimes relapse years after treatment. However, Drs. James Armitage of the University of Nebraska Medical Center and Dan Longo of Harvard Medical School, in an accompanying editorial, expressed optimism that nivolumab–AVD could provide durable remissions.  

The study also opens the door to new research opportunities in the area. Investigators are currently analyzing tumor DNA levels in blood samples from participants to explore whether these biomarkers can further refine treatment strategies. Additionally, ongoing studies aim to assess the potential of combining nivolumab with other therapies, such as brentuximab, to create even more effective treatment regimens.  

Changing the Standard of Care  

Although the FDA has yet to approve nivolumab for use in this specific setting, experts believe that clinical guidelines for Hodgkin lymphoma treatment will soon reflect the findings of this trial.

This shift could have far-reaching implications, particularly for adolescents and older patients, who often face unique challenges in Hodgkin lymphoma treatment. By offering a more effective and less toxic option, the nivolumab–AVD treatment is a significant advancement in the field.  

A Brighter Future for Hodgkin Lymphoma Patients  

As research continues, the introduction of nivolumab into first-line therapy may be the beginning of a new era in Hodgkin lymphoma treatment. With improved survival rates, fewer side effects, and a reduced reliance on radiation therapy, this approach has the potential to transform outcomes for thousands of patients each year.