A recent clinical trial has revealed that incorporating nivolumab (Opdivo) into the initial treatment for advanced classic Hodgkin lymphoma yields superior outcomes compared to the current standard regimen. The study, funded by the National Cancer Institute (NCI), demonstrated that nivolumab combined with AVD chemotherapy (doxorubicin, vinblastine, and dacarbazine) significantly improves cancer elimination and sustained remission in teens and adults.
The trial, involving nearly 1,000 participants, compared nivolumab-AVD to brentuximab-AVD, the existing standard first-line treatment. After two years, approximately 92% of patients in the nivolumab-AVD group experienced progression-free survival, compared to 83% in the brentuximab-AVD group, according to findings published in the New England Journal of Medicine.
Improved Progression-Free Survival and Reduced Toxicity
The study's lead investigator, Dr. Jonathan Friedberg, Director of the Wilmot Cancer Institute at the University of Rochester, emphasized the potential for increased cure rates with the nivolumab-AVD regimen. Historically, most patients with advanced Hodgkin lymphoma who remain cancer-free two years post-treatment are considered cured. The new regimen also significantly reduced the need for radiation therapy, particularly beneficial for adolescents, minimizing long-term side effects such as secondary cancers.
"We've largely eliminated radiation therapy as part of the [initial] treatment," Dr. Friedberg stated. "We now have a more effective, less toxic regimen that should not only have fewer short-term side effects, but also fewer long-term side effects."
Shifting from Brentuximab to Nivolumab
Brentuximab-AVD has been the standard initial treatment for advanced Hodgkin lymphoma for about a decade. While it modestly improves progression-free survival, it is associated with significant side effects, including peripheral neuropathy and gastrointestinal issues, often leading to treatment discontinuation. Nivolumab is already used as a second-line treatment for relapsed Hodgkin lymphoma, demonstrating promising results that prompted its evaluation as part of the initial therapy.
The SWOG Cancer Research Network conducted the trial across multiple hospitals in the United States, ensuring diverse representation with 12% Black and 13% Hispanic participants. This inclusivity enhances the general applicability of the findings. The trial also included adolescents aged 12 to 17, addressing the need for tailored treatment strategies in this age group.
Impact on Clinical Practice
Despite the significant improvement in progression-free survival, overall survival rates at two years were similar between the two groups (99% vs. 98%), which is expected given the short follow-up period. However, the reduction in severe side effects and treatment-related deaths in the nivolumab-AVD group underscores its clinical advantage. Specifically, peripheral neuropathy was markedly less frequent in the nivolumab arm.
Dr. Paul Harker-Murray of Children’s Wisconsin anticipates that the nivolumab-AVD regimen will become the new standard of care for adolescents and young adults with Hodgkin lymphoma at many cancer centers. Experts like Drs. James Armitage and Dan Longo noted that the trial challenges the assumption that the ability to cure advanced Hodgkin lymphoma had been maximized.
Implications for Older Patients
The study's findings are particularly relevant for patients aged 60 and older, who typically experience poorer treatment outcomes. The two-year progression-free survival rate of 88% in this age group treated with nivolumab-AVD is considered a significant improvement. Furthermore, the brentuximab-AVD regimen had an unacceptable side-effect profile in older patients, with one-third discontinuing treatment early.
While Bristol Myers Squibb, the manufacturer of nivolumab, has not commented on plans for FDA approval for this specific use, Dr. Friedberg expects that expert guidelines will be revised to recommend nivolumab-AVD as the preferred initial treatment for advanced Hodgkin lymphoma.
