The results of the SWOG S1826 clinical trial, presented at the 2023 ASCO Annual Meeting, demonstrated that the combination of the immune checkpoint inhibitor OPDIVO (nivolumab) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) significantly reduced the risk of disease progression and disease-related death in pediatric and adult patients with previously untreated stage III or IV Hodgkin lymphoma, compared to standard treatment with ADCETRIS (brentuximab vedotin) plus AVD. The study, funded by the National Cancer Institute, enrolled 976 patients aged 12 years and older.
With a median follow-up of 12.1 months, the trial showed a 52% reduction in the risk of disease-related death with nivolumab compared to brentuximab vedotin. The 1-year progression-free survival rate was 94% for nivolumab and 86% for brentuximab vedotin. Adverse events were limited with nivolumab, primarily consistent with the side effects seen with combination chemotherapies, such as low blood cell counts and gastrointestinal toxicities like nausea. Immune-related adverse events were infrequent.
These findings suggest that the addition of nivolumab to chemotherapy could become a new standard of care for previously untreated advanced-stage Hodgkin lymphoma patients, providing improved outcomes and a manageable safety profile.
KOL insights
“This trial was an unprecedented effort across all North American clinical trial cooperative groups to improve the cure rate in advanced-stage Hodgkin lymphoma and harmonize treatment approaches between pediatric and adult patients. The collaborations across adult and pediatric groups helped pave the way for a new standard of care that is better tolerated and results in a higher proportion of patients with durable remissions” –Expert Opinion.
“At the second planned interim analysis, the primary PFS endpoint crossed the protocol-specified statistical boundary, signifying that the trial had met its primary endpoint. Nivolumab/AVD reduced the risk of disease progression or death by [approximately] half” –Expert Opinion.
“This is a practice-changing study given the favorable efficacy and toxicity associated with nivolumab/AVD. This study included children, adolescents, adults, and elderly patients, all of whom benefited from nivolumab/AVD. Adolescent and young adult [AYA] patients are treated in both the pediatric and adult settings. Having the same treatment recommendations by both sets of providers is important” –Expert Opinion.
Conclusion
Ongoing follow-up in the SWOG S1826 trial aims to confirm the durability of PFS, evaluate overall survival, and assess patient-reported outcomes. However, based on the results presented, the combination of nivolumab and AVD chemotherapy is expected to become a new standard therapy for the treatment of advanced-stage classic Hodgkin lymphoma, applicable to patients of all age groups. This represents an important milestone in aligning the treatment approach for pediatric and adult patients with classic Hodgkin lymphoma.
