What is the recommended treatment approach for a 60-year-old male with stage 3 Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) and no B symptoms?

Treatment Approach for Stage 3 Nodular Lymphocyte-Predominant Hodgkin Lymphoma in a 60-Year-Old Male

For a 60-year-old male with stage 3 Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) without B symptoms, ABVD chemotherapy (with bleomycin discontinued after the second cycle) followed by localized radiotherapy to residual disease is the recommended treatment approach.

Understanding NLPHL and Its Treatment Principles

NLPHL is a distinct entity from classical Hodgkin Lymphoma (cHL), characterized by:

• CD20-positive malignant cells (unlike classical HL)
• Generally indolent clinical course
• Different treatment approaches for different stages

For stage 3 NLPHL, the ESMO guidelines clearly state:

• "NLPHL is treated identically to cHL in all patients except for those with stage IA disease presenting without clinical risk factors" 1
• This means advanced-stage NLPHL follows the same treatment protocols as classical HL

Treatment Algorithm for a 60-Year-Old with Stage 3 NLPHL

First-Line Treatment:

1. ABVD chemotherapy regimen

   • Six cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
   • Important safety modification: "Bleomycin should be discontinued after the second ChT cycle in this patient group [>60 years]" 1
   • This modification is critical as it reduces pulmonary toxicity risk while maintaining efficacy

2. Response assessment:

   • PET-CT after 2 cycles and at completion of chemotherapy
   • "Interim staging to exclude disease progression during treatment and to stratify treatment if PET–CT is available" 1

3. Consolidation radiotherapy:

   • "Additional RT is confined to the patients with residual disease after ChT" 1
   • Target PET-positive residual lymphoma ≥2.5 cm

Key Treatment Considerations

1. Age-specific recommendations:

   • At 60 years old, the patient falls into the "older patient" category per ESMO guidelines
   • "The BEACOPP regimen should not be given to the patients > 60 years" 1
   • "ABVD-based ChT represents the standard of care for older HL patients who are fit enough for multi-agent ChT" 1

2. CD20 expression in NLPHL:

   • While rituximab has shown activity in NLPHL due to CD20 expression 2, 3, the guidelines still recommend ABVD as first-line therapy for advanced-stage disease
   • Rituximab is primarily recommended for localized relapses: "Localised NLPHL relapses can be effectively treated with anti-CD20 antibodies such as rituximab" 1

Monitoring and Follow-up

After completion of treatment:

• Physical examination, laboratory analyses, and contrast-enhanced CT are mandatory 1
• PET-CT should be conducted if available 1
• Regular follow-up schedule: every 3 months for first half year, every 6 months until fourth year, then annually 1
• Monitor for late effects:
  • Thyroid function annually if neck was irradiated
  • Testosterone levels should be monitored
  • Regular cancer screening due to secondary malignancy risk

Management of Relapse

If relapse occurs:

• Obtain a renewed biopsy to confirm NLPHL (rule out transformation) 1
• For localized relapse: single-agent rituximab 1, 3
• For disseminated relapse: more aggressive salvage chemotherapy combined with anti-CD20 antibody 1
• High-dose chemotherapy followed by autologous stem cell transplantation for patients with early disease recurrence or poor-risk features 4

Prognosis

The overall prognosis for NLPHL is excellent compared to other lymphomas, with:

• Lower excess mortality compared to the general population 4
• Potential for long-term disease control
• Main concern is the risk of transformation to aggressive B-cell lymphoma, which occurs in a subset of patients 3

This treatment approach balances efficacy against toxicity concerns, particularly important in a 60-year-old patient where long-term complications must be carefully considered.