What is the role of the Nivo (nivolumab) AVD (Adriamycin (doxorubicin), Vinblastine, Dacarbazine) regimen in the treatment of Hodgkin lymphoma?

Role of Nivolumab-AVD in the Treatment of Hodgkin Lymphoma

Nivolumab plus AVD (doxorubicin, vinblastine, dacarbazine) is now the preferred first-line regimen for advanced-stage classical Hodgkin lymphoma, demonstrating superior progression-free survival compared to brentuximab vedotin plus AVD with a better side effect profile.

Evidence for Nivolumab-AVD in Advanced Hodgkin Lymphoma

The most recent and highest quality evidence comes from a phase 3, multicenter, randomized trial published in the New England Journal of Medicine in 2024 1. This landmark study compared nivolumab with AVD (N+AVD) to brentuximab vedotin with AVD (BV+AVD) in patients with stage III or IV newly diagnosed Hodgkin lymphoma. The results were compelling:

• N+AVD significantly improved progression-free survival compared to BV+AVD (hazard ratio 0.45)
• 2-year progression-free survival was 92% with N+AVD vs 83% with BV+AVD
• N+AVD had a better side effect profile with less treatment discontinuation
• Minimal need for consolidative radiation therapy (only 7 patients required it)

This represents a major advancement over previous standard regimens like ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or BV+AVD.

Earlier Evidence Supporting Nivolumab in Hodgkin Lymphoma

The CheckMate 205 trial (Cohort D) 2 provided initial evidence for nivolumab's role in newly diagnosed advanced-stage Hodgkin lymphoma. This phase II study evaluated nivolumab monotherapy followed by N-AVD and showed:

• 84% objective response rate with 67% complete remission
• 92% 9-month modified progression-free survival
• Manageable safety profile with 59% experiencing grade 3-4 treatment-related adverse events
• Endocrine immune-mediated adverse events were all grade 1-2

Treatment Algorithm for Hodgkin Lymphoma

Based on the current evidence, here is the recommended approach:

1. Early-stage favorable disease: 2 cycles of ABVD + 20 Gy involved-site radiation therapy (ISRT) 3

2. Early-stage unfavorable disease: 4 cycles of ABVD + 30 Gy ISRT 3

3. Advanced-stage disease (Stage III-IV):

   • First choice: Nivolumab + AVD based on superior PFS and better side effect profile 1
   • Alternative: 6 cycles of ABVD or escalated BEACOPP for patients <60 years with high-risk features 4
   • For patients >60 years: Avoid BEACOPP due to increased treatment-related mortality 4

4. Relapsed/refractory disease:

   • High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) 4
   • Brentuximab vedotin for consolidation after ASCT in high-risk patients 4
   • Nivolumab or pembrolizumab for patients who relapse after ASCT and brentuximab vedotin 4

Special Considerations and Toxicity Management

• PET-guided approach: Interim PET assessment after 2 cycles can guide subsequent therapy 4
• Bleomycin toxicity: Consider omitting bleomycin after cycle 2 in patients >60 years when using ABVD 4
• Immune-related adverse events: Monitor for and promptly manage immune-related adverse events with nivolumab 2
• Fertility preservation: Recommend before initiation of alkylating agents or pelvic radiation 4

Caveats and Pitfalls

• The long-term follow-up data for nivolumab-AVD is still maturing, though early results are very promising 1
• Immune-related adverse events require vigilant monitoring and prompt management
• Treatment selection must balance efficacy with both short and long-term toxicity profiles
• Older patients (>60 years) require special consideration due to increased risk of treatment-related toxicity
• Radiation therapy remains an important component for early-stage disease but may be less necessary with newer regimens for advanced disease

The evidence strongly supports nivolumab-AVD as the new standard of care for advanced Hodgkin lymphoma based on improved efficacy and tolerability compared to previous regimens.