On March 20, 2026, the US FDA approved Opdivo (nivolumab) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for adult and pediatric patients aged 12 years and older with previously untreated, Stage III or IV classical Hodgkin lymphoma. The approval, granted to Bristol Myers Squibb, makes nivolumab the first PD-1 checkpoint inhibitor authorized for frontline use in advanced classical Hodgkin lymphoma, a disease that affects approximately 8,500 to 9,000 people annually in the United States. Concurrently, the FDA converted nivolumab's prior accelerated approvals from 2016 and 2017 for relapsed or refractory classical Hodgkin lymphoma to traditional approval. The application received priority review and orphan drug designation, and was reviewed under Project Orbis in collaboration with regulatory agencies in Israel, Australia, Canada, and Switzerland.
The approval covers nivolumab at 240 mg for adults and pediatric patients weighing 40 kg or more, or 3 mg/kg for those under 40 kg, administered intravenously on Days 1 and 15 of each 28-day cycle for up to six cycles in combination with AVD. Primary G-CSF prophylaxis is recommended starting in Cycle 1. The traditional approval conversion applies to two previously accelerated indications in adults with relapsed or refractory disease: after autologous hematopoietic stem cell transplantation and brentuximab vedotin, and after three or more lines of systemic therapy including autologous transplantation.
The approval rests on results from SWOG S1826 (Study CA209-8UT), a randomized, open-label, multicenter Phase III trial that enrolled 994 patients aged 12 years and older with previously untreated Stage III or IV classical Hodgkin lymphoma. Patients were randomized 1:1 to receive either nivolumab plus AVD or brentuximab vedotin plus AVD for six cycles. The primary endpoint was investigator-assessed progression-free survival. The nivolumab arm demonstrated a hazard ratio of 0.42 (95% CI: 0.27–0.67; p<0.0001), corresponding to a 58% reduction in the risk of progression or death. Median progression-free survival was not reached in either arm after a median follow-up of 13.7 months. At a median follow-up of 36.7 months, deaths occurred in 1.8% of patients receiving nivolumab plus AVD compared with 3.4% in the brentuximab vedotin arm. Serious adverse reactions occurred in 39% of patients in the nivolumab arm, with immune-mediated adverse reactions reported in 9% of patients, of which 2.7% were Grade 3 or 4.
This approval alters the treatment landscape for advanced classical Hodgkin lymphoma, where brentuximab vedotin (Adcetris, Seagen/Pfizer) combined with AVD had been the standard first-line regimen since its approval in 2018 based on the ECHELON-1 trial. The SWOG S1826 trial was designed as a direct head-to-head comparison between the two regimens, and the magnitude of the progression-free survival difference was substantial. For Bristol Myers Squibb, the approval extends Opdivo's reach into a new line of therapy for a disease where it previously held indications only in the relapsed or refractory setting. Classical Hodgkin lymphoma disproportionately affects adolescents and young adults, a population for whom long-term treatment toxicity is a persistent concern. Both the nivolumab and brentuximab vedotin combination regimens use AVD rather than the older ABVD backbone, eliminating bleomycin and its associated pulmonary toxicity. The field continues to evolve, with investigational approaches including CD30-directed CAR-T cell therapies, dual checkpoint blockade with agents such as favezelimab plus pembrolizumab (Merck), and anti-CD25 antibody-drug conjugates such as camidanlumab tesirine (ADC Therapeutics) in development for relapsed or refractory disease. An open question is how to manage patients who relapse after receiving PD-1 inhibitor-based frontline therapy, a clinical scenario that will become more common as this regimen enters routine practice.
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