ABVD Protocol for Intermediate-Stage Hodgkin Lymphoma
The standard treatment for intermediate-stage Hodgkin lymphoma is 4 cycles of ABVD chemotherapy followed by 30 Gy involved-site radiotherapy (ISRT). 1
ABVD Regimen Dosing
The ABVD protocol consists of the following drugs administered intravenously on days 1 and 15, with cycles repeating every 29 days: 1
- Doxorubicin: 25 mg/m² IV
- Bleomycin: 10 mg/m² IV
- Vinblastine: 6 mg/m² IV
- Dacarbazine: 375 mg/m² IV
PET-Adapted Treatment Strategy
After 2 Cycles of ABVD
Interim PET-CT scanning after 2 cycles determines subsequent treatment intensity. 1
Negative interim PET (Deauville score ≤2): Complete the remaining 2 cycles of ABVD, then proceed to 30 Gy ISRT 1
Positive interim PET (Deauville score ≥3): Switch to 2 cycles of BEACOPPescalated before ISRT to reduce relapse risk 1
The H10 study demonstrated significantly reduced relapse rates when patients with positive interim PET escalated to BEACOPPescalated rather than continuing ABVD. 1
Radiotherapy Considerations
ISRT at 30 Gy is the recommended radiation field after chemotherapy for intermediate-stage disease. 1 While ILROG guidelines recommend ISRT over the older involved-field radiotherapy (IFRT), this has not been validated in randomized trials comparing the two approaches. 1
Omitting Radiotherapy
A critical caveat: Chemotherapy alone (without radiotherapy) is NOT standard of care for intermediate-stage disease. 1 The H10 trial failed to demonstrate non-inferiority of chemotherapy alone compared to combined-modality treatment, even in patients with negative interim PET (Deauville ≤2). 1 However, chemotherapy alone may be considered in select patients when the late toxicity risks of radiotherapy are judged to outweigh the short-term disease control benefits, recognizing this represents a deviation from standard care. 1
Age-Specific Modifications
Patients ≤60 Years
For fit patients ≤60 years eligible for intensive treatment, an alternative regimen of 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD and 30 Gy RT showed superior freedom from treatment failure compared to standard 4 cycles of ABVD plus RT, though no overall survival advantage was demonstrated. 1
Patients >60 Years
Bleomycin must be discontinued after the second cycle in patients >60 years due to substantially increased risk of bleomycin-induced pulmonary toxicity in this age group. 1 Complete the remaining cycles with AVD only (doxorubicin, vinblastine, dacarbazine). 1
Older patients experience significantly higher toxicity with ABVD: treatment-related mortality reaches 5%, only 59% achieve ≥80% relative dose-intensity (versus 85% in younger patients), and treatment delays average 2.2 weeks (versus 1.2 weeks in younger patients). 2
BEACOPPescalated Regimen (When Indicated)
When escalation is required based on positive interim PET, the BEACOPPescalated regimen consists of: 1
- Bleomycin: 10 mg/m² IV on day 8
- Etoposide: 200 mg/m² IV on days 1-3
- Doxorubicin: 35 mg/m² IV on day 1
- Cyclophosphamide: 1250 mg/m² IV on day 1
- Vincristine: 1.4 mg/m² IV on day 8 (maximum 2 mg absolute dose)
- Procarbazine: 100 mg/m² PO on days 1-7
- Prednisone: 40 mg/m² PO on days 1-14
- G-CSF: subcutaneous starting day 8
Cycles repeat every 22 days. 1
Critical Pitfalls to Avoid
Do not use BEACOPPescalated in patients >60 years due to excessive toxicity and treatment-related mortality in this population. 1 Standard ABVD (with bleomycin limited to 2 cycles) remains the appropriate regimen for older patients. 1
Do not omit radiotherapy based solely on negative interim PET in intermediate-stage disease, as this approach failed to demonstrate non-inferiority in the H10 trial. 1
Monitor closely for bleomycin pulmonary toxicity, particularly in patients receiving more than 2 cycles and those >60 years. 1, 2