The addition of nivolumab to AVD chemotherapy (N-AVD) has shown superior progression-free survival (PFS) compared to the standard brentuximab vedotin plus AVD (BV-AVD) in patients with advanced classical Hodgkin lymphoma (cHL). The SWOG S1826 trial (NCT03907488) presented at the NCCN 2024 Annual Congress by Dr. Iris Isufi, indicates that N-AVD also boasts a more favorable toxicity profile, especially for patients 60 years and older.
The SWOG S1826 trial, a randomized study, assigned newly diagnosed patients with stage III or IV Hodgkin lymphoma to either N-AVD (nivolumab, doxorubicin, vinblastine, and dacarbazine) or BV-AVD (brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine). The results demonstrated a significant improvement in 1-year PFS rates with N-AVD at 94% (95% CI, 91%-96%) compared to 86% (95% CI, 82%-90%) for BV-AVD (HR, 0.48; 99% CI, 0.27–0.87; P = .0005).
Efficacy and Safety Outcomes
Event-free survival (EFS) rates at 1 year were also higher in the N-AVD arm at 91% (95% CI, 88%-94%) versus 84% (95% CI, 80%-88%) in the BV-AVD arm (HR, 0.56; 99% CI, 0.33-0.95). Overall survival (OS) rates at 1 year were 95% (range, 83%-99%) in the N-AVD arm versus 83% (range, 67%-92%) in the BV-AVD arm (HR, 0.35; 95% CI, 0.07-1.75; P = .091). Notably, the 1-year PFS rate for patients 60 years or older was 93% in the N-AVD arm versus 64% in the BV-AVD arm (HR, 0.35; 95% CI, 0.12-1.02; P = .022).
Regarding safety, hematologic adverse events (AEs) of any grade in the N-AVD versus BV-AVD arms included neutropenia (55% vs 32%), anemia (38% vs 44%), and thrombocytopenia (10% vs 17%). Infectious AEs showed no increase in infectious toxicity in the N-AVD arm. Immune-related AEs, such as transaminitis, were similar between the two arms. Hypothyroidism was more common in the N-AVD arm (7%), but mostly low grade.
Trial Design and Patient Population
In the trial, patients received either 240 mg of nivolumab or 1.2 mg/kg of brentuximab vedotin on days 1 and 15 of each cycle for 6 cycles, along with AVD chemotherapy. Granulocyte colony-stimulating factor was required for the BV-AVD arm but optional for the N-AVD arm. The primary endpoint was PFS, and secondary endpoints included EFS, OS, end-of-treatment complete metabolic response, and patient-reported outcomes.
Patient demographics were well balanced, with a median age of 27 years. The study included diverse populations, with 77% White, 12% Black, and 2% Asian participants. Key eligibility criteria included being 12 years or older, controlled HIV positivity, and adequate organ function. Exclusion criteria included interstitial lung disease, peripheral neuropathy, and active autoimmune disease.
Current Treatment Landscape and Future Directions
Dr. Isufi highlighted that while the ABVD regimen has been a standard treatment for advanced HL, it carries a risk of bleomycin-induced pulmonary toxicity. The BV-AVD regimen, as studied in the ECHELON-1 trial, improved OS compared to ABVD but may present increased toxicity in older patients. The HD21 trial explored BrECADD, showing high response rates and better tolerability than eBEACOPP.
Dr. Isufi concluded that data from these trials, including SWOG S1826, will inform future studies on de-escalation of therapy and tailoring treatment to individual patient needs, considering their fitness level, comorbidities, and ability to perform daily activities.
