What are the current treatment recommendations for Hodgkin's lymphoma based on landmark trials?

Landmark Trials and Current Treatment Recommendations for Hodgkin Lymphoma

Based on landmark clinical trials, ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) remains the standard chemotherapy backbone for most patients with Hodgkin lymphoma, with treatment regimens tailored according to disease stage and risk factors. 1, 2

Disease Classification and Staging

• Classical Hodgkin lymphoma (cHL) comprises four subtypes:

  • Nodular sclerosis
  • Mixed cellularity
  • Lymphocyte depletion
  • Lymphocyte-rich

• Staging follows the Ann Arbor system with Cotswolds modifications

• PET/CT is essential for initial staging and response assessment 1

Treatment Recommendations by Stage

Early-Stage Favorable Disease

• Standard treatment: 2 cycles of ABVD followed by 20 Gy involved-site radiation therapy (ISRT) 1, 2
• The GHSG HD10 trial established that 2 cycles of ABVD + 20 Gy ISRT is as effective as 4 cycles + 30 Gy ISRT, with reduced toxicity 2
• PET-guided approaches are being evaluated but not yet standard of care 1

Early-Stage Unfavorable Disease

• Standard treatment: 4 cycles of ABVD followed by 30 Gy ISRT 1
• The GHSG HD11 trial established this regimen as standard 2
• Unfavorable features include: B symptoms, bulky disease, elevated ESR, >3 involved nodal sites 1

Advanced-Stage Disease (Stage III-IV)

• Standard treatment options:

  1. 6 cycles of ABVD (standard in many countries) 1
  2. Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for patients <60 years with high-risk features 1, 3

• The landmark CALGB trial demonstrated ABVD superiority over MOPP (mechlorethamine, vincristine, procarbazine, prednisone) 1

• The HD9 trial by the German Hodgkin Study Group showed improved progression-free survival with escalated BEACOPP compared to ABVD, but with higher toxicity 1, 3

• The RATHL trial demonstrated that omitting bleomycin after negative interim PET (switching to AVD) maintains efficacy while reducing pulmonary toxicity 1

Relapsed/Refractory Disease

• Standard approach: Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) 1, 4
• Common salvage regimens include DHAP, ESHAP, ICE, or gemcitabine combinations 1
• Brentuximab vedotin (BV) is approved for patients who relapse after ASCT 1, 4
• Checkpoint inhibitors (nivolumab, pembrolizumab) show promising results in multiply relapsed patients 1

Key Clinical Trials That Shaped Current Practice

1. ABVD Development: Established as standard regimen with superior efficacy and less toxicity than MOPP 1

2. GHSG HD10: Demonstrated 2 cycles ABVD + 20 Gy ISRT is sufficient for early favorable disease 2

3. GHSG HD11: Established 4 cycles ABVD + 30 Gy ISRT for early unfavorable disease 2

4. GHSG HD9: Showed escalated BEACOPP improves disease control in advanced disease 1, 3

5. RATHL: Demonstrated PET-adapted approach allows bleomycin omission after negative interim PET 1

6. ECHELON-1: Evaluated brentuximab vedotin plus AVD vs. ABVD in advanced disease 1

7. CheckMate and KEYNOTE trials: Established efficacy of checkpoint inhibitors in relapsed/refractory disease 1

Special Considerations

• Toxicity concerns: Treatment selection must balance efficacy with short and long-term toxicity

  • Bleomycin can cause pulmonary toxicity
  • BEACOPP causes higher rates of infertility and myelosuppression 2
  • Radiation therapy increases risk of secondary malignancies and cardiovascular disease 1

• Age-specific approaches:

  • BEACOPP should be avoided in patients >60 years due to increased treatment-related mortality 1, 2
  • Dose modifications may be needed for elderly patients 1

• Response assessment:

  • PET/CT is crucial for interim and end-of-treatment evaluation 1
  • Deauville score is used to interpret PET results and guide subsequent management 1

Hodgkin lymphoma remains one of the most curable malignancies, with overall survival rates exceeding 80% 5. Treatment selection should be guided by disease stage, risk factors, and patient characteristics, with the goal of maximizing cure while minimizing long-term toxicity.