What are the current treatment approaches for Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)?

Treatment Approaches for Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

NLPHL treatment should be stage-based, with involved-site radiotherapy alone for stage IA disease without risk factors, while all other stages require combined modality approaches or chemotherapy regimens incorporating anti-CD20 antibodies. 1

Diagnosis and Staging

• Excisional lymph node biopsy is essential for diagnosis
• Required diagnostic workup includes:
  • Complete medical history and physical examination
  • Contrast-enhanced CT scan of neck, chest, and abdomen
  • PET scan (baseline)
  • Complete blood count and blood chemistry
  • Hepatitis B, C, and HIV screening
  • ECG, echocardiography, and pulmonary function tests

Treatment Algorithm by Stage

Stage IA without Risk Factors

• 30 Gy ISRT alone is the standard treatment 2
• This approach has excellent outcomes with minimal toxicity
• Note: The ISRT fields for this RT-alone approach are larger than those used in combined-modality approaches to include potential microscopic regional disease

All Other Stages (Stage IA with Risk Factors, IB-IV)

• NLPHL is treated identically to classical HL in all patients except for those with stage IA disease without risk factors 2

• Treatment options include:

  1. Combined modality treatment:

     • 4 cycles of ABVD followed by 30 Gy ISRT 1
     • Alternative: 2 cycles of ABVD followed by 20 Gy ISRT

  2. Chemotherapy regimens (with CD20-targeting):

     • ABVD ± rituximab
     • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
     • CVP ± rituximab
     • EPOCH ± rituximab

• R-CHOP has shown particularly promising results due to the consistent CD20 expression on LP cells 1, 3

Management of Relapsed/Refractory Disease

1. Obtain a renewed biopsy before initiating salvage therapy to rule out transformation to aggressive disease 2

2. Treatment options based on extent of relapse:

   • Localized relapses: Anti-CD20 antibodies (rituximab or ofatumumab) as single agent 2
   • More disseminated disease with poor-risk features: More aggressive salvage chemotherapy combined with anti-CD20 antibody 2
   • For high-risk patients: High-dose chemotherapy followed by autologous stem cell transplantation 2, 1

3. Salvage therapy should be individualized based on:

   • Time to relapse
   • Extent of disease at relapse
   • Prior treatment 2

4. Salvage regimens include:

   • DHAP, IGEV, or ICE (to reduce tumor burden and mobilize stem cells)
   • Single-agent brentuximab vedotin (for patients failing ASCT)
   • Nivolumab and pembrolizumab (for patients with disease recurrence after HDCT followed by ASCT and brentuximab vedotin therapy)

Response Evaluation and Follow-up

• Interim staging to exclude disease progression during treatment

• Final staging after completion of treatment with:

  • Physical examination
  • Laboratory analyses
  • Contrast-enhanced CT
  • PET-CT (if available)

• Follow-up schedule:

  • Every 3 months for first 6 months
  • Every 6 months until 4th year
  • Annually thereafter 2

• Additional monitoring:

  • Annual thyroid function tests if neck was irradiated
  • Testosterone and estrogen levels in younger patients who had intensive chemotherapy
  • Regular cancer screening due to increased risk of secondary malignancies

Important Considerations and Caveats

• NLPHL has an excellent overall survival rate (80-90% can be considered cured) 2
• Late relapses may occur, requiring long-term follow-up
• Risk of transformation to aggressive large B-cell lymphoma necessitates rebiopsy at relapse
• Treatment should aim to minimize long-term toxicity while maintaining excellent survival outcomes
• Avoid BEACOPPescalated regimen in patients >60 years due to increased treatment-related mortality 1
• Consider omitting bleomycin after cycle 2 in ABVD, especially in patients >60 years or with lung disease 1

By following this stage-based approach with appropriate consideration of CD20 expression, NLPHL patients can achieve excellent outcomes with minimal long-term toxicity.