Researchers have found that the combination of nivolumab plus doxorubicin, vinblastine, and dacarbazine (AVD) may reduce the risk of cancer progression and mortality in patients with Hodgkin lymphoma compared with standard treatment, according to a recent study published by Herrera et al in The New England Journal of Medicine.
Background
In mid-2023, the phase III SWOG S1826 trial in advanced Hodgkin lymphoma reported highly positive primary results, earlier than expected, after the trial’s second planned interim analysis found the preset threshold for efficacy had already been reached.
Study Methods and Results
In a follow-up analysis of the SWOG S1826 trial, the researchers examined the outcomes of 970 adolescent and adult patients with newly diagnosed with Hodgkin lymphoma who received either nivolumab plus AVD or standard treatment with brentuximab vedotin plus AVD.
After a median follow-up of 2.1 years, the researchers confirmed the durability of their initial findings. The patients who received nivolumab plus AVD had a significantly lower risk of cancer progression or mortality compared with those who received brentuximab vedotin plus AVD.
Compared with the patients in the brentuximab vedotin plus AVD group, the patients in the nivolumab plus AVD group experienced 2-year progression free survival rates of 92% vs 83%. This benefit was generally consistent across prespecified patient subgroups, including by age, disease stage, and International Prognostic Score.
Overall, the nivolumab plus AVD treatment was better tolerated compared with the brentuximab vedotin plus AVD treatment. For instance, compared with those in the brentuximab vedotin plus AVD group, fewer patients in the nivolumab plus AVD group stopped treatment early (7.6% vs 12.0%) and experienced death during treatment (0.6% vs 1.7%). The rates of most side effects were also lower in the nivolumab plus AVD group.
The differences in toxicity between the two treatments were particularly pronounced in patients older than 60 years of age. In the brentuximab vedotin plus AVD group, the rate of mortality was higher compared with younger patients, and roughly one-third of them had to discontinue treatment early because of toxicity; whereas patients older than 60 years in the nivolumab plus AVD group did not experience significantly higher morbidity or mortality rates compared with their younger counterparts. Notably, less than 1% of patients received radiation therapy.
Conclusions
“This new analysis with more patient follow-up is critical to understanding the clinically meaningful benefit obtained from [nivolumab plus] AVD compared [with standard treatment],” underscored co–study author Michael LeBlanc, PhD, Professor of Biostatistics at Fred Hutch Cancer Center, Director of the SWOG Statistics and Data Management Center, and a lead biostatician at the SWOG Cancer Research Network.
The researchers hope their findings can enable earlier evaluation of promising novel therapies in adolescent patients with Hodgkin lymphoma in the front-line setting.
Disclosure: The research in this study was funded by the National Institutes of Health/National Cancer Institute (NCI), with additional support provided by Bristol Myers Squibb through a Cooperative Research and Development Agreement with the NCI. For full disclosures of the study authors, visit nejm.org.
