Nivolumab Regimen for Relapsed or Refractory Hodgkin Lymphoma
The CheckMate 205 trial established the nivolumab regimen for relapsed or refractory Hodgkin lymphoma. This pivotal phase 2 study demonstrated high response rates and durable remissions in patients who had failed autologous stem cell transplantation and brentuximab vedotin therapy 1, 2, 3.
Trial Design and Patient Population
The CheckMate 205 trial (NCT02181738) was a single-arm, open-label, multicenter, multicohort study that evaluated nivolumab in patients with classical Hodgkin lymphoma 4. The study included three cohorts:
- Cohort A: Brentuximab vedotin-naïve patients
- Cohort B: Patients who received brentuximab vedotin after autologous stem cell transplantation
- Cohort C: Patients who received brentuximab vedotin before and/or after autologous stem cell transplantation
Patients received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity 4, 1.
Efficacy Results
The CheckMate 205 trial demonstrated impressive efficacy:
- Overall response rate (ORR): 71.2% (95% CI, 65.1-76.8%)
- Complete remission rate: 21.4% (95% CI, 16.4-27.1%)
- Median duration of response: 18.2 months
- 5-year overall survival: 71.4% 1
These results were consistent across all three cohorts, with ORRs ranging from 65% to 73% 3.
Long-term Follow-up Data
With extended follow-up (median ~5 years), the CheckMate 205 trial showed:
- Durable responses in approximately 50% of patients
- Median progression-free survival of 15.1 months
- No new or unexpected safety signals 1
FDA Approval
Based on the results of CheckMate 205, the FDA approved nivolumab for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin 4.
Mechanism of Action
Nivolumab works by blocking the programmed death-1 (PD-1) pathway, which is frequently exploited by Reed-Sternberg cells in Hodgkin lymphoma through genetic alterations in chromosome 9p24.1 that increase the abundance of PD-1 ligands 2.
Safety Profile
The most common adverse events in the CheckMate 205 trial included:
- Sensory peripheral neuropathy
- Neutropenia
- Immune-related adverse events requiring corticosteroids (29% of patients) 5
No treatment-related deaths were observed in the trial 5.
Clinical Application
For patients with relapsed or refractory Hodgkin lymphoma who have failed autologous stem cell transplantation and brentuximab vedotin, nivolumab represents an effective treatment option with durable responses and manageable toxicity 6.
Emerging Combination Approaches
Recent studies are exploring nivolumab in combination with other agents:
- Nivolumab plus brentuximab vedotin as consolidation therapy after autologous HSCT has shown promising results with 18-month progression-free survival of 94% 5
- Nivolumab followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) is being studied in newly diagnosed advanced-stage Hodgkin lymphoma 7
The CheckMate 205 trial has definitively established nivolumab as an effective treatment for relapsed or refractory Hodgkin lymphoma, offering new hope for patients with limited treatment options.