What are the recommended regimens for relapsed or refractory Hodgkin lymphoma?

Recommended Regimens for Relapsed or Refractory Hodgkin Lymphoma

The standard of care for relapsed or refractory Hodgkin lymphoma is high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), with brentuximab vedotin as the preferred option for patients who fail ASCT or are not ASCT candidates. 1

First-Line Salvage Therapy Options

For Transplant-Eligible Patients:

• Salvage chemotherapy regimens (prior to ASCT):
  • DHAP (dexamethasone/high-dose cytarabine/cisplatin) 1
  • IGEV (ifosfamide/gemcitabine/vinorelbine) 1
  • ICE (ifosfamide/carboplatin/etoposide) 1
  • Brentuximab vedotin + bendamustine (highly active combination with 92.5% objective response rate and 73.6% complete response rate) 2

Response Assessment:

• Achieving a negative PET scan before ASCT is crucial for improved outcomes 1
• Patients with chemosensitive disease have significantly better outcomes after ASCT compared to those with resistant disease 1

Post-ASCT Options:

For High-Risk Patients After ASCT:

• Brentuximab vedotin maintenance for 1 year as consolidation therapy for patients at high risk of relapse 1, 3

For Patients Who Relapse After ASCT:

• Brentuximab vedotin (FDA-approved for patients who relapse after ASCT) 1, 3
• PD-1 inhibitors:
  • Nivolumab (71.2% overall response rate, 21.4% complete remission rate) 4
  • Pembrolizumab (FDA-approved for relapsed/refractory classical Hodgkin lymphoma) 5

For Transplant-Ineligible Patients:

Patients Not Eligible for ASCT:

• Brentuximab vedotin (FDA-approved for patients who have failed at least two prior therapies) 1, 3
• Bendamustine (active in heavily pre-treated patients) 1, 6
• Brentuximab vedotin + bendamustine combination (75% overall response rate, well-tolerated) 7, 6
• PD-1 inhibitors (nivolumab or pembrolizumab) 4, 5

Special Situations:

Localized Late Relapse:

• Salvage radiotherapy alone may be sufficient 1

Low-Risk Patients with Early Relapse After Limited Initial Therapy:

• More intensive conventional chemotherapy (e.g., BEACOPPescalated) may be effective 1

For Multiple Relapses:

After Failure of Multiple Lines of Therapy:

• Allogeneic stem cell transplantation for young, chemosensitive patients in good general condition 1
• Palliative options:
  • Gemcitabine-based chemotherapy 1
  • Regional radiotherapy 1
  • Rituximab (for CD20-expressing cases) 1
  • HDAC inhibitors (e.g., panobinostat) 1

Clinical Pearls and Pitfalls:

1. Key pitfall: Continuing with additional salvage chemotherapy beyond two lines in chemoresistant patients may select for highly resistant lymphoma clones. Instead, consider targeted therapies like brentuximab vedotin or PD-1 inhibitors 1.

2. Important consideration: Brentuximab vedotin should not be given with bleomycin due to increased risk of pulmonary toxicity 8.

3. Prognostic factors at relapse that influence treatment decisions include:

   • Refractoriness to initial therapy
   • Short disease-free interval
   • Disseminated disease 1

4. Monitoring for toxicity: When using brentuximab vedotin with bendamustine, premedication is recommended to reduce infusion-related reactions, which commonly occur during cycle 2 2.

The treatment landscape for relapsed/refractory Hodgkin lymphoma continues to evolve, with targeted therapies like brentuximab vedotin and PD-1 inhibitors showing impressive response rates and improving survival outcomes for patients who previously had limited options.