What are the latest treatment guidelines and protocols for Hodgkin's lymphoma?

Latest Treatment Guidelines and Protocols for Hodgkin's Lymphoma

For Hodgkin's lymphoma treatment, the most effective approach is stage-based therapy with PET-guided treatment intensification, using ABVD or BEACOPPescalated regimens based on disease stage and patient factors. 1

Diagnosis and Staging

• Excisional lymph node biopsy is the gold standard for diagnosis 2
• Required diagnostic workup includes:
  • Medical history and physical examination
  • Contrast-enhanced CT scan of neck, chest, and abdomen
  • PET scan
  • Complete blood count and blood chemistry
  • Hepatitis B, C, and HIV screening
  • ECG, echocardiography, and pulmonary function tests 1

Treatment by Disease Stage

Limited Stage Disease (Stage I-II without risk factors)

• Standard treatment: 2 cycles of ABVD followed by 20 Gy involved-site radiotherapy (ISRT) 1
• Alternative: 3-4 cycles of ABVD alone may be considered for patients with concerns about radiation toxicity

Intermediate Stage Disease (Stage I-II with risk factors)

• Standard treatment: 4 cycles of ABVD followed by 30 Gy ISRT 1
• Alternative intensified approach: 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD and 30 Gy ISRT (superior freedom from treatment failure compared to ABVD) 1
• PET-guided approach:
  • If interim PET (after 2 cycles) is negative (Deauville score ≤2): continue with planned therapy
  • If interim PET is positive (Deauville score ≥3): switch to 2 cycles of BEACOPPescalated before ISRT 1

Advanced Stage Disease (Stage III-IV)

• For patients ≤60 years:
  • Option 1: 6 cycles of ABVD with bleomycin omission after cycle 2 if interim PET is negative 1
  • Option 2: 4-6 cycles of BEACOPPescalated (superior overall survival compared to ABVD, with 10% survival advantage at 5 years) 3
  • PET-guided approach after 2 cycles:
    • If PET-negative after BEACOPPescalated: only 2 more cycles needed
    • If PET-positive after BEACOPPescalated: 4 more cycles needed 1
    • If PET-positive after ABVD: consider switching to BEACOPPescalated 1
• For patients >60 years:
  • 6-8 cycles of ABVD with bleomycin discontinuation after cycle 2 1
  • BEACOPP regimen should NOT be used due to increased treatment-related mortality 1

Radiotherapy Considerations

• After BEACOPPescalated: RT can be restricted to PET-positive residual lymphoma >2.5 cm 1
• After ABVD: Consider RT for residual masses >1.5 cm 1
• Modern field design uses involved-site radiotherapy (ISRT) rather than older involved-field radiotherapy (IFRT) 1

Relapsed/Refractory Disease Management

1. First-line salvage therapy:

   • High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard of care 1
   • Salvage regimens include DHAP, IGEV, or ICE to reduce tumor burden and mobilize stem cells 1
   • Aim for negative PET before ASCT for best outcomes 1

2. Post-ASCT consolidation:

   • Brentuximab vedotin consolidation is recommended for patients with high-risk features 1, 4

3. Subsequent relapses:

   • Brentuximab vedotin for patients failing ASCT 1, 4
   • Checkpoint inhibitors (nivolumab, pembrolizumab) for patients who relapse after ASCT and brentuximab vedotin 1
   • Allogeneic stem cell transplantation for young, chemosensitive patients in good condition 1
   • Gemcitabine-based palliative chemotherapy and/or regional RT for multiple relapses with no other options 1

Special Considerations

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

• Stage IA without risk factors: 30 Gy ISRT alone 1
• All other stages: treat identically to classical HL 1
• Relapsed NLPHL:
  • Obtain biopsy to exclude transformation to aggressive NHL 1
  • Localized relapses: anti-CD20 antibodies (rituximab, ofatumumab) 1
  • More disseminated relapses: more aggressive salvage chemotherapy possibly with anti-CD20 antibody 1

Response Evaluation and Follow-up

• Interim PET-CT after 2 cycles to guide treatment decisions 1
• Final staging after completion of treatment with physical exam, labs, and contrast-enhanced CT 1
• Follow-up schedule:
  • Every 3 months for first 6 months
  • Every 6 months until 4th year
  • Annually thereafter 1
• Monitor for late effects including second malignancies and cardiac toxicity 2

Common Pitfalls and Caveats

• Bleomycin toxicity: Consider omitting bleomycin after cycle 2 in ABVD, especially in patients >60 years or with lung disease 1
• BEACOPPescalated toxicity: Higher rates of infertility, myelosuppression, and infections; requires G-CSF support 1
• Avoid BEACOPPescalated in patients >60 years due to increased treatment-related mortality 1
• Brentuximab vedotin contraindication: Concomitant use with bleomycin due to pulmonary toxicity 4