Nivolumab-AVD Regimen for Newly Diagnosed Advanced-Stage Hodgkin Lymphoma
Nivolumab-AVD (N-AVD) is an effective regimen for newly diagnosed advanced-stage Hodgkin lymphoma, combining the anti-PD-1 monoclonal antibody nivolumab with doxorubicin, vinblastine, and dacarbazine, demonstrating promising efficacy with a 9-month modified progression-free survival rate of 92%. 1
Composition and Administration
The N-AVD regimen consists of:
- Nivolumab: 240 mg intravenously every 2 weeks
- Doxorubicin (Adriamycin): 25 mg/m² intravenously on days 1 and 15
- Vinblastine: 6 mg/m² intravenously on days 1 and 15
- Dacarbazine: 375 mg/m² intravenously on days 1 and 15
The regimen is administered in 28-day cycles, with treatment typically consisting of 6 cycles 1, 2.
Clinical Evidence and Efficacy
The CheckMate 205 trial (Cohort D) evaluated nivolumab monotherapy followed by N-AVD in patients with newly diagnosed advanced-stage Hodgkin lymphoma. Results showed:
- Objective response rate of 84% with 67% achieving complete remission
- 9-month modified progression-free survival of 92%
- Higher programmed death-ligand 1 (PD-L1) expression on Hodgkin Reed-Sternberg cells was associated with more favorable responses 1
In older adults (≥60 years), a phase II trial of N-AVD demonstrated:
- 3-year progression-free survival of 79%
- 3-year overall survival of 97%
- Efficacy maintained across patients with various geriatric impairments 2
Safety Profile
The N-AVD regimen has shown a manageable safety profile:
- Grade 3-4 treatment-related adverse events occur in approximately 50-59% of patients
- Most common significant adverse events include:
- Febrile neutropenia (8-10%)
- Elevated liver enzymes (ALT increased in 11%)
- Peripheral sensory neuropathy (primarily grade 1-2)
- Immune-mediated adverse events are generally manageable, with endocrine events typically grade 1-2 1, 2
Patient Selection and Considerations
N-AVD may be particularly beneficial for:
- Patients with newly diagnosed advanced-stage (III-IV) Hodgkin lymphoma
- Older adults (≥60 years) who may not tolerate more intensive regimens
- Patients where bleomycin avoidance is desirable due to pulmonary concerns
Monitoring and Management
During N-AVD treatment:
- Regular monitoring of complete blood counts is essential
- Liver function tests should be performed before each cycle
- Thyroid function tests are recommended due to potential immune-related endocrinopathies
- PET-CT evaluation is typically performed after 2 cycles and at the end of treatment 3
- Granulocyte colony-stimulating factor (G-CSF) prophylaxis should be considered to reduce neutropenia risk 4
Comparison to Standard Regimens
While ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) has been the traditional standard for advanced Hodgkin lymphoma 3, N-AVD offers potential advantages:
- Omission of bleomycin may reduce pulmonary toxicity risk
- Addition of nivolumab may improve efficacy through immune-mediated mechanisms
- Potentially better tolerated in older patients compared to more intensive regimens like BEACOPPescalated 5, 2
Cautions and Limitations
- Long-term follow-up data are still limited
- Immune-related adverse events require vigilant monitoring
- Cost considerations may impact accessibility
- Potential for unexpected toxicities when combining immunotherapy with chemotherapy 6
N-AVD represents an evolving treatment approach for advanced Hodgkin lymphoma that warrants consideration, particularly in settings where enhanced efficacy with manageable toxicity is desired.