What are the treatment options for Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)?

Treatment Options for Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

For NLPHL, treatment should be stage-based with involved-site radiotherapy (ISRT) alone for stage IA disease without risk factors, while all other stages should be treated with combined modality approaches or chemotherapy regimens that incorporate anti-CD20 antibodies. 1, 2

Treatment by Stage

Stage IA without Risk Factors

• ISRT at 30 Gy alone is the standard treatment 1
• Note that ISRT fields in this approach are larger than those used in combined-modality approaches to address potential microscopic regional disease 1

Early Stage (Other than Stage IA)

• Combined modality treatment with:
  • 2 cycles of ABVD followed by 20 Gy ISRT 2
  • OR 4 cycles of ABVD followed by 30 Gy ISRT 1, 2

Intermediate and Advanced Stages

• Treatment approaches similar to classical Hodgkin lymphoma, but with consideration for CD20 expression 1
• Recommended regimens:
  • ABVD ± rituximab 1, 2
  • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) 1
  • CVP ± rituximab 1
  • EPOCH ± rituximab 1

Role of Anti-CD20 Therapy

The malignant lymphocyte-predominant (LP) cells in NLPHL consistently express CD20, unlike classical Hodgkin lymphoma, making anti-CD20 antibodies particularly relevant 1, 3:

• The addition of rituximab to conventional chemotherapy has shown promising results 1
• R-CHOP has demonstrated particularly good outcomes in retrospective studies 1
• Single-agent rituximab is an option for select patients, particularly in relapsed disease 1, 4

Relapsed/Refractory Disease

For relapsed NLPHL:

• Biopsy is essential to exclude transformation to aggressive non-Hodgkin lymphoma 2
• Treatment options include:
  • Anti-CD20 antibodies (rituximab) for localized relapses 2, 4
  • Conventional chemotherapy 3
  • Radiotherapy for previously unirradiated sites 3
  • High-dose chemotherapy with autologous stem cell transplantation only for patients with poor-risk features (early disease recurrence) 3

Treatment Considerations and Caveats

1. Long-term survival: NLPHL has excellent overall survival with 10-year estimates of approximately 95% 4, requiring careful consideration of long-term toxicities

2. Risk of transformation: NLPHL can transform to aggressive large B-cell lymphoma, necessitating long-term follow-up 5

3. Late relapses: NLPHL has a tendency for late relapses, requiring extended monitoring 5

4. Watchful waiting: May be appropriate in select cases, particularly in pediatric patients, but early treatment appears more beneficial in terms of progression-free survival 4

5. Follow-up schedule:

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

Treatment Algorithm

1. Confirm diagnosis through excisional lymph node biopsy with CD20+ and CD30- LP cells 2, 3

2. Complete staging with PET/CT, laboratory tests, and bone marrow biopsy if PET/CT unavailable 2

3. Determine treatment based on stage:

   • Stage IA without risk factors: ISRT 30 Gy alone
   • Early stage with risk factors: Combined modality (chemotherapy + ISRT)
   • Advanced stage: Chemotherapy with anti-CD20 antibodies (R-CHOP or ABVD+R)

4. Monitor for relapse and transformation with regular follow-up examinations and imaging when clinically indicated

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