What is the preferred first-line treatment regimen, ABVD (Adriamycin (Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine) or Nivolumab (Opdivo) AVD, for a patient with Hodgkin lymphoma?

Nivolumab-AVD vs ABVD for First-Line Hodgkin Lymphoma

Nivolumab-AVD is the preferred first-line treatment for advanced-stage classical Hodgkin lymphoma based on superior progression-free survival and elimination of bleomycin-related pulmonary toxicity, though ABVD remains standard for limited and intermediate stages where combined modality therapy is used.

Critical Evidence Gap

The provided evidence does not include the pivotal S1826 trial (NEJM 2023) comparing nivolumab-AVD to ABVD in advanced-stage Hodgkin lymphoma. However, I must make treatment recommendations based on the evidence hierarchy and clinical context:

Treatment Selection by Stage

Limited-Stage Disease (Stage I-II)

• ABVD remains standard: 2-4 cycles of ABVD followed by involved-site radiotherapy (20-30 Gy) 1, 2
• Nivolumab-AVD has not been adequately studied in limited-stage disease where combined modality therapy is the backbone 1
• The brief chemotherapy exposure (2-4 cycles) minimizes bleomycin toxicity risk in this population 1, 2

Intermediate-Stage Disease (Stage I-II with Risk Factors)

• ABVD remains standard: 4 cycles of ABVD followed by 30 Gy involved-site radiotherapy 1, 2
• For patients ≤60 years eligible for intensive therapy, 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD and 30 Gy radiotherapy may be considered 1
• Nivolumab-AVD data in this population with planned radiotherapy is insufficient 1, 2

Advanced-Stage Disease (Stage III-IV)

This is where the paradigm has shifted:

For Patients ≤60 Years

• Nivolumab-AVD is preferred based on the S1826 trial showing superior progression-free survival and elimination of bleomycin pulmonary toxicity risk (though this specific trial is not in the provided evidence)
• Alternative: 6-8 cycles of ABVD with interim PET-guided response adaptation 2, 3
• BEACOPPescalated may be considered for International Prognostic Score ≥3, but carries significantly higher toxicity including permanent infertility 3, 4

For Patients >60 Years

• ABVD remains standard: 6-8 cycles followed by 30 Gy radiotherapy to residual masses >1.5 cm 1, 3
• BEACOPPescalated is contraindicated due to excessive treatment-related mortality 1, 3
• Nivolumab-AVD data in elderly patients is limited but would theoretically be safer than ABVD due to bleomycin elimination

Key Toxicity Considerations

ABVD Toxicity Profile

• Bleomycin pulmonary toxicity: 5-10% incidence, potentially fatal 3
• Cardiotoxicity from doxorubicin 3
• Myelosuppression (though rarely severe) 1
• Critical: G-CSF prophylaxis is NOT recommended with ABVD as it may increase bleomycin pulmonary toxicity risk 3
• Fertility preservation: ABVD rarely causes permanent infertility 3

Nivolumab-AVD Toxicity Profile (Based on General Knowledge)

• Eliminates bleomycin pulmonary toxicity risk
• Immune-related adverse events (thyroiditis, pneumonitis, colitis)
• Peripheral neuropathy from vinblastine
• Infusion reactions
• No increased infertility risk compared to ABVD

Response-Adapted Strategy with ABVD

If ABVD is chosen for advanced disease:

• Perform interim PET after 2-4 cycles using Deauville 5-point scale 3
• Deauville 1-3: Continue ABVD to complete 6-8 cycles; consider ISRT (30 Gy) for initial sites >5 cm 3
• Deauville 4: Continue ABVD with ISRT 3
• Deauville 5: Biopsy recommended; if positive, manage as refractory disease 3

Expected Outcomes

ABVD in Advanced Disease

• 5-year overall survival: 82-85% 3
• Complete remission rates: 76-80% 3
• Primary refractory disease: approximately 18% 5

Limited/Intermediate Disease with ABVD

• Complete response rates: 82-94% 2
• 5-year progression-free survival: >90% with combined modality therapy 1, 2

Common Pitfalls to Avoid

• Never use G-CSF prophylaxis with ABVD - increases bleomycin toxicity without survival benefit 3
• Do not confuse vincristine (used in BEACOPP) with vinblastine (used in ABVD) - vinblastine 6 mg/m² is the correct vinca alkaloid for ABVD 2, 6
• BEACOPPescalated should not be used in patients >60 years due to excessive mortality 1, 3
• Ensure baseline pulmonary function testing before ABVD to identify patients at increased risk for bleomycin toxicity 1
• Offer fertility preservation counseling before treatment, especially with BEACOPPescalated which causes permanent infertility 1, 3