FDA Approves Frontline Nivolumab/AVD in Late-Stage Hodgkin Lymphoma

The FDA has approved nivolumab (Opdivo) plus doxorubicin, vinblastine, and dacarbazine (AVD) for the treatment of adult and pediatric patients aged 12 and older with treatment-naive stage III or IV classical Hodgkin lymphoma (cHL).¹

With this approval, the FDA has also converted its accelerated approvals to standard approvals for nivolumab in patients who have previously received autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin (Adcetris), as well as in patients who have received at least 3 prior lines of systemic therapy, including autologous HSCT.

Frontline Findings

The safety and efficacy of nivolumab/AVD was assessed in the randomized, open-label, multicenter trial CA209-8UT (NCT03907488), in which 994 patients 12 years and older with treatment-naive stage III or IV cHL were randomly assigned 1:1 to receive either nivolumab/AVD or brentuximab vedotin/AVD for 6 cycles.

Findings demonstrated a significant progression-free survival (PFS) benefit for patients in the nivolumab arm, decreasing the risk of disease progression or death by 58% (HR, 0.42; 95% CI, 0.27-0.67; P <.0001). After a median follow-up of 13.7 months, median PFS was reached in neither arm. With a median follow-up of 36.7 months, 1.8% of patients died in the nivolumab arm vs 3.4% in the brentuximab vedotin arm.

Nivolumab is recommended at 240 mg for both adult patients and pediatric patients weighing at least 40 kg. For pediatric patients weighing less than 40 kg, the recommended dose is 3 mg/kg. Nivolumab should be administered intravenously with AVD on days 1 and 15 of a 28-day cycle for up to 6 cycles.

Safety Precautions

It is recommended that patients receive granulocyte-colony stimulating factor (G-CSF) prophylaxis starting at cycle 1.

In CA209-8U, serious adverse events (AEs) occurred in 39% of patients, and immune-mediated AEs occurred in 9% of patients, including grade 3 or 4 events occurring in 2.7% of patients.

Previous findings from the trial published in The New England Journal of Medicine demonstrated that common any-grade adverse effects (AEs) in the nivolumab and brentuximab vedotin arms, respectively, included nausea (65% vs 70%), fatigue (47% vs 51%), neutrophil count decreases (56% vs 34%), anemia (39% vs 46%), and peripheral sensory neuropathy (29% vs 56%).²

Further, rates of pneumonitis, gastritis, rash, and colitis were comparable between treatment arms. The rate of treatment discontinuation was higher in the brentuximab vedotin arm, according to investigators.

“Nivolumab with AVD chemotherapy is a well-tolerated and highly effective new standard of care for patients with stage III or IV Hodgkin lymphoma. It’s critical to be able to offer these patients a safe and effective therapy that can put their cancer into long-term remission,” lead study author Alex Herrera, MD, chief of the Division of Lymphoma at City of Hope in Duarte, California, stated in a press release on these findings.³ “With these promising results, we expect nivolumab with AVD chemotherapy will become a new standard of care and the first treatment we provide patients who are diagnosed with advanced-stage Hodgkin lymphoma.”

Patients in the nivolumab arm had a median age was 27.6 years (range, 12.0-83.7) compared with 26.8 years (range, 12.0-81.7) in the brentuximab vedotin arm.² Additionally, 44% and 43% of patients in each arm were female. In respective arms, the majority of patients were White (76% vs 75%), had stage IV disease (62% vs 65%), and had International Prognostic Scores of 0 to 3 (68% vs 68%).

References

1. FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma. March 20, 2026. Accessed March 20, 2026. FDA. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-chemotherapy-previously-untreated-hodgkin-lymphoma
2. Herrera AF, LeBlanc M, Castellino SM, et al. Nivolumab+AVD in advanced-stage classic Hodgkin’s lymphoma. N Engl J Med. 2024;391(15):1379-1389. doi:10.1056/NEJMoa2405888
3. Marquez L. Longer-term data from SWOG S1826 trial confirms nivolumab-AVD benefit in Hodgkin lymphoma. News release. City of Hope. October 16, 2024. Accessed October 17, 2024. https://tinyurl.com/yjenkzub