What is the recommended first-line treatment for patients with Hodgkin lymphoma, particularly in the context of the SWOG S1826 trial?

First-Line Treatment for Hodgkin Lymphoma: SWOG S1826 Trial Context

The recommended first-line treatment for Hodgkin lymphoma depends on disease stage and risk factors, with ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) remaining a standard regimen for many patients, while BEACOPP escalated offers superior outcomes in advanced disease for younger patients. 1

Disease Classification and Risk Stratification

Treatment approaches vary based on:

• Classical Hodgkin Lymphoma (cHL) vs Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)
• Disease stage (early favorable, early unfavorable, advanced)
• Presence of risk factors
• Patient age and comorbidities

Risk Factors to Assess

• Bulky disease
• B symptoms (fever, night sweats, weight loss)
• Elevated ESR
• Multiple nodal sites
• Extranodal involvement

Treatment Recommendations by Stage

Early Favorable Disease (Stage I-II without risk factors)

• Standard approach: Combined modality treatment with 2-4 cycles of ABVD followed by 20-30 Gy involved-field radiotherapy (IFRT) 1
• For stage IA NLPHL specifically: 30 Gy IFRT alone 2

Early Unfavorable Disease (Stage I-II with risk factors)

• Standard approach: 4 cycles of ABVD followed by 30 Gy IFRT 1
• Alternative experimental approaches include:
  • BEACOPP escalated
  • Reduced radiation dose (20 Gy)
  • Chemotherapy-only approaches

Advanced Disease (Stage III-IV)

• Standard options:

  1. 6-8 cycles of ABVD (standard in many countries) 1
  2. 6-8 cycles of BEACOPP escalated (superior response rates of 96%, disease-free survival 88%, overall survival 92% at 5 years) 1

• Important considerations:

  • BEACOPP escalated should be reserved for patients <60 years due to higher toxicity 1, 2
  • For elderly patients (>60 years), 6-8 cycles of ABVD is recommended 1
  • Bleomycin carries significant pulmonary toxicity risk; consider omitting after cycle 2, especially in patients >60 years or with lung disease 2, 3

SWOG S1826 Trial Context

The SWOG S1826 trial is evaluating novel approaches in Hodgkin lymphoma treatment, reflecting the evolving landscape that includes:

• PET-guided response-adapted therapy to potentially reduce treatment intensity in good responders 1
• Integration of novel agents like brentuximab vedotin and PD-1 inhibitors into frontline regimens 4, 5
• Strategies to reduce long-term toxicities while maintaining high cure rates 5

Treatment Considerations for Special Populations

Elderly Patients

• Avoid BEACOPP escalated due to increased treatment-related mortality 2
• Consider bleomycin omission after cycle 2 in ABVD 2

Relapsed/Refractory Disease

• High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is standard for chemotherapy-sensitive relapse 1, 6
• Brentuximab vedotin is approved for patients failing ASCT or with multiple relapses 1, 7
• PD-1 inhibitors (nivolumab, pembrolizumab) show high efficacy in relapsed/refractory disease 5

Monitoring and Follow-up

• PET-CT for response assessment during and after treatment 1
• Regular follow-up: every 3 months for first year, every 6 months for years 2-3, then annually 2
• Monitor for late effects:
  • Thyroid function if neck was irradiated
  • Cardiac and pulmonary toxicity
  • Secondary malignancies
  • Fertility issues in younger patients 1, 2

Treatment Toxicity Considerations

• Bleomycin: Pulmonary toxicity increases dramatically with total doses over 400 units 3
• BEACOPP escalated: Higher rates of infertility, myelosuppression, and infections 2
• Vinblastine: Used in ABVD regimen at 0.25-0.50 units/kg (10-20 units/m²) weekly or twice weekly for Hodgkin's disease 8

Hodgkin lymphoma treatment has evolved significantly, with current cure rates of 80-90% 1, 6. The ongoing SWOG S1826 trial represents continuing efforts to optimize treatment approaches, balancing efficacy with minimizing long-term toxicity.