Nivolumab Plus AVD Approved by FDA as Frontline Therapy for Advanced cHL

The U.S. Food and Drug Administration has approved nivolumab (Opdivo, Bristol Myers Squibb) in combination with the chemotherapy regimen doxorubicin, vinblastine, and dacarbazine (AVD) for the treatment of adults and pediatric patients aged 12 years and older with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL). The decision introduces an immunotherapy-based regimen for patients with newly diagnosed advanced disease.

Regulatory clearance was supported by data from the Phase 3 SWOG S1826 study (NCT03907488), which enrolled 994 patients with previously untreated Stage III or IV cHL. In the open-label trial, participants were randomly assigned to receive nivolumab plus AVD or a comparator regimen of brentuximab vedotin combined with AVD, each administered for six treatment cycles. Results from the SWOG S1826 trial were previously reported in the New England Journal of Medicine

Results from the study showed a significant improvement in progression-free survival for the nivolumab-based regimen. Treatment with nivolumab plus AVD reduced the risk of disease progression or death by 58% compared with brentuximab vedotin plus AVD (hazard ratio 0.42; 95% CI: 0.27–0.67; p<0.0001). Median progression-free survival had not been reached in either treatment group at the time of the primary analysis, which occurred after a median follow-up of 13.7 months. With extended follow-up of 36.7 months, deaths were reported in 1.8% of patients receiving nivolumab plus AVD and 3.4% of those treated with the comparator regimen.

The safety profile observed in the trial was consistent with previous experience with nivolumab. Serious adverse events were reported in 39% of patients treated with the nivolumab combination, while immune-mediated adverse reactions occurred in 9% of patients, including 2.7% that were Grade 3 or 4 in severity.

Under the approved regimen, nivolumab is administered intravenously at a dose of 240 mg for adults and pediatric patients weighing at least 40 kg, or 3 mg/kg for patients weighing less than 40 kg. The treatment is given on Days 1 and 15 of each 28-day cycle together with AVD chemotherapy for a maximum of six cycles. Prophylactic use of granulocyte colony-stimulating factor is recommended beginning with the first treatment cycle.

In addition to the frontline indication, the FDA converted nivolumab’s earlier accelerated approvals in relapsed or refractory classical Hodgkin lymphoma to traditional approvals. The drug is now fully approved for adults whose disease has progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, as well as for patients who have received at least three prior systemic treatment regimens that include autologous HSCT.

The regulatory review was conducted under Project Orbis, a collaborative framework led by the FDA Oncology Center of Excellence that enables simultaneous review of oncology medicines across multiple international regulators. Participating agencies for this review included the Israeli Ministry of Health, Australia’s Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic.

The application was granted priority review and orphan drug designation by the FDA.

Reference

FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma, 20 March 2026, FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma | FDA

Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma, ClinicalTrials.gov ID NCT03907488, https://clinicaltrials.gov/study/NCT03907488

Herrera AF et al, Nivolumab+AVD in Advanced-Stage Classic Hodgkin’s Lymphoma. N Engl J Med. 2024 Oct 17;391(15):1379-1389. PMID: 39413375; PMCID: PMC11488644. https://doi.org/10.1056/nejmoa2405888