What is the initial treatment approach for a patient with Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)?

Initial Treatment Approach for Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

For patients with NLPHL, the initial treatment approach should be determined by disease stage, with stage IA without risk factors treated with 30 Gy involved-site radiotherapy (ISRT) alone, while all other stages should receive treatment similar to classical Hodgkin lymphoma with consideration of adding rituximab due to CD20 expression on LP cells. 1

Treatment Algorithm by Stage

Stage IA without Risk Factors

• First-line treatment: 30 Gy ISRT alone 1
• No chemotherapy needed for this limited presentation
• Excellent outcomes with radiation therapy alone

Early Stage (IA with risk factors, IB, IIA)

• First-line treatment: Combined modality approach
  • 2-3 cycles of ABVD chemotherapy followed by 20-30 Gy ISRT 1
  • Consider adding rituximab to chemotherapy regimen due to CD20 expression on LP cells 1

Intermediate Stage (IIB, IIIA)

• First-line treatment: Combined modality approach
  • 4 cycles of ABVD followed by 30 Gy ISRT 1
  • Consider adding rituximab to chemotherapy regimen 1, 2

Advanced Stage (IIIB, IV)

• First-line treatment: Chemotherapy alone, typically:
  • 6 cycles of ABVD or
  • R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) 2, 3
  • Additional RT confined to patients with residual disease after chemotherapy 1

Important Clinical Considerations

Diagnostic Confirmation

• Ensure proper diagnosis with detection of lymphocyte-predominant (LP) cells 1
• LP cells consistently express CD20 (unlike classical Hodgkin lymphoma) but do not express CD30 3

Staging Workup

• Mandatory: Contrast-enhanced CT scan of neck, chest, and abdomen 1
• Baseline PET-CT if available 1
• Full blood count, ESR testing, and blood chemistry analysis 1
• Screening for HBV, HCV, and HIV 1

Response Assessment

• Interim staging to exclude disease progression during treatment 1
• Final staging after completion of treatment with:
  • Physical examination
  • Laboratory analyses
  • Contrast-enhanced CT
  • PET-CT if available 1

Prognostic Factors

• NLPHL generally has an excellent prognosis with low excess mortality compared to the general population 3
• Most patients experience long-term survival 4
• Risk of transformation to aggressive lymphoma must be considered in follow-up 1

Follow-up Protocol

• Every 3 months for the first half year
• Every 6 months until the fourth year
• Once a year thereafter 1, 2
• CT scans should be performed once to confirm remission status, with additional imaging only if suspicious clinical symptoms occur 2

Treatment Efficacy Evidence

• R-CHOP has shown promising results in NLPHL, particularly in advanced stages 2, 5
• The addition of rituximab to conventional chemotherapy has demonstrated good outcomes in retrospective studies 6, 7
• In a retrospective study of 314 patients, combined modality treatment showed 4-year PFS of 93.9%, compared to 79.6% with radiotherapy alone, 77.0% with rituximab alone, and 78.8% with chemotherapy or immunochemotherapy 7

Pitfalls and Caveats

• Always obtain a renewed biopsy in suspected NLPHL relapse before initiating salvage therapy, as transformation to aggressive disease may occur 1
• Avoid watchful waiting in symptomatic patients as early treatment significantly reduces the risk of progression 7
• Consider the risk of secondary malignancies in treatment planning and follow-up 2
• Monitor thyroid function annually if the neck was irradiated 1

By following this treatment algorithm based on disease stage and incorporating rituximab for CD20-positive disease, patients with NLPHL can achieve excellent outcomes with appropriate therapy tailored to their specific presentation.