Initial Treatment for Hodgkin Lymphoma
The initial treatment for Hodgkin lymphoma is risk-stratified based on stage and prognostic factors, with ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) forming the backbone of therapy, combined with involved-field radiotherapy for early-stage disease, while advanced-stage disease requires 6-8 cycles of ABVD or escalated BEACOPP in younger patients. 1
Risk Stratification
Before initiating treatment, patients must be allocated to one of three risk groups based on Ann Arbor staging and specific risk factors 1:
- Early favorable: Stage I-II without risk factors 1
- Early unfavorable: Stage I-II with risk factors (large mediastinal mass >1/3 horizontal chest diameter, extranodal disease, ESR >50 with B symptoms or >30 without, ≥3 involved lymph node areas) 1
- Advanced: Stage III-IV, or stage IIB with large mediastinal mass or extranodal involvement 1
Treatment by Risk Group
Early Favorable Disease (Stage I-II without risk factors)
Standard treatment consists of 2 cycles of ABVD followed by 30 Gy involved-field radiotherapy. 1 This approach is based on the German Hodgkin Study Group HD7 and HD10 trials, which demonstrated that 2 cycles of ABVD is not inferior to 4 cycles when combined with radiotherapy, while substantially reducing toxicity 1. The addition of chemotherapy to radiotherapy significantly reduces relapse rates compared to radiotherapy alone 1.
An alternative chemotherapy-only approach using 4-6 cycles of ABVD can be considered, though prospective randomized trial data supporting this approach remains limited 1.
Early Unfavorable Disease (Stage I-II with risk factors)
Standard treatment is 4 cycles of ABVD followed by 30 Gy involved-field radiotherapy. 1 This achieves tumor control and overall survival exceeding 85-90% at 5 years 1. The Italian Society of Hematology guidelines confirm that 4 cycles of ABVD followed by involved-field radiotherapy represents the standard for this intermediate-stage risk group 1.
Recent evidence demonstrates that 4 cycles of ABVD followed by involved-site radiotherapy (ISRT) produces excellent outcomes even in patients with bulky disease, with 6-year freedom from relapse of 100% and no deaths, suggesting that 6 cycles does not provide superior disease control 2.
Advanced-Stage Disease (Stage III-IV)
For patients under 60 years, 8 cycles of BEACOPP escalated is considered standard by the German Hodgkin Study Group, achieving superior outcomes with 96% overall response, 88% disease-free survival, and 92% overall survival at 5 years. 1 A 2014 network meta-analysis including 9,993 patients confirmed a 10% survival advantage at 5 years with BEACOPP escalated compared to ABVD 1.
However, due to significantly higher acute toxicity, 6-8 cycles of ABVD remains the standard regimen in many countries and is mandatory for patients over 60 years, as increased treatment-related mortality has been observed in this age group with BEACOPP. 1 ABVD achieves long-term cure rates of 50-60% in advanced disease 1.
Additional radiotherapy to initial tumor bulks or residual disease <2.5 cm after chemotherapy is not generally recommended outside clinical trials 1. Larger residual tumors that are PET-positive should receive additional radiotherapy 1.
Special Considerations
Lymphocyte Predominant Hodgkin Lymphoma (LPHL)
Stage I LPHL can be treated with involved-field radiotherapy (30 Gy) alone 1. Rituximab is an option for relapsed LPHL 1.
Patients with Significant Comorbidities
For patients with chronic liver disease, acute kidney injury, or cardiomyopathy, modified ABVD without bleomycin is recommended to avoid pulmonary toxicity 3. BEACOPP is absolutely contraindicated in the setting of organ dysfunction 3. Dose adjustments for renally cleared agents based on creatinine clearance are necessary 3.
Common Pitfalls
- Avoid radiotherapy alone: Multiple randomized trials (SWOG, GHSG HD7, EORTC H7 and H8) have definitively shown that combined modality therapy is superior to radiotherapy alone, with 5-year freedom from progression of 93% versus 70% 1.
- Do not routinely use 6 cycles for early unfavorable disease: Evidence shows 4 cycles of ABVD with radiotherapy is equally effective and less toxic, even for bulky disease 2.
- Recognize BEACOPP toxicity: While more effective, BEACOPP escalated requires appropriate surveillance and supportive care infrastructure, and should never be used in patients over 60 years 1.
- Bleomycin pulmonary toxicity: More patients experience bleomycin pulmonary toxicity with 6 cycles (31%) versus 4 cycles (20%) 2.