Nivolumab Plus Chemotherapy Approved for Previously Untreated Hodgkin Lymphoma
Expert Perspectives
By Lyn Brook
Published
The FDA granted approval to nivolumab (Opdivo®, Bristol Myers Squibb Company) 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 (cHL). In addition, the FDA converted prior accelerated approvals of nivolumab to traditional approval for adults with relapsed or refractory cHL for the following indications:
Following autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin
Following three or more lines of systemic therapy that include autologous HSCT
Why This Approval Matters
Frontline treatment of advanced cHL has historically relied on multi-agent chemotherapy, with brentuximab vedotin plus AVD emerging as a commonly used regimen. The incorporation of nivolumab, a PD-1 immune checkpoint inhibitor, into first-line therapy offers a chemotherapy-immunotherapy approach that significantly improves progression-free survival while maintaining a manageable safety profile. This approval provides a new standard option for patients with advanced-stage disease and further reinforces the role of PD-1 blockade across multiple lines of therapy in cHL.
Breaking Down SWOG 1826 (CA209-8UT)
Efficacy of nivolumab plus AVD was evaluated in SWOG 1826 (NCT03907488), a phase 3, open-label, multicenter trial enrolling 994 patients aged 12 years and older with previously untreated stage III or IV cHL. Patients were randomized 1:1 to receive:
Experimental arm: nivolumab plus AVD for six cycles
Control arm: brentuximab vedotin plus AVD for six cycles
The primary end point was progression-free survival (PFS) as assessed by investigators.
Results demonstrated a significant improvement in PFS with nivolumab plus AVD:
PFS: Median PFS was not reached in either arm at a median follow-up of 13.7 months
Survival: At a median follow-up of 36.7 months, deaths occurred in 1.8% of patients in the nivolumab plus AVD arm compared with 3.4% in the control arm
Managing Adverse Events
Serious adverse events occurred in 39% of patients receiving nivolumab plus AVD, and 9% of patients reported experiencing immune-mediated adverse events (grade 3–4 in 2.7%).
Nivolumab carries warnings and precautions for:
Immune-mediated adverse reactions (eg, pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions)
Infusion-related reactions
Complications of allogeneic HSCT
Embryo-fetal toxicity
Dosing and Administration
The recommended nivolumab dosing when used with AVD is:
Adults and pediatric patients ≥40 kg: 240 mg IV
Pediatric patients <40 kg: 3 mg/kg IV
Nivolumab is administered on Days 1 and 15 of each 28-day cycle in combination with AVD, for up to six cycles. Primary G-CSF prophylaxis should be initiated starting in Cycle 1.
Resources
Clinicaltrials.gov (2025). Immunotherapy (nivolumab or brentuximab vedotin) plus combination chemotherapy in treating patients with newly diagnosed stage III-iv classic Hodgkin lymphoma. NLM identifier: NCT03907488.