What is the treatment regimen of choice and associated side effects for Classical Hodgkin Lymphoma (CHL) Stage IIIB post-biopsy?

Treatment of Classical Hodgkin Lymphoma Stage IIIB

For Classical Hodgkin Lymphoma Stage IIIB, the regimen of choice is 6 cycles of ABVD chemotherapy alone, with radiotherapy reserved only for PET-positive residual disease ≥2.5 cm after completion of chemotherapy. 1

Primary Treatment Approach

Standard Regimen: ABVD

For patients ≤60 years with advanced-stage disease (including Stage IIIB), ABVD for 6 cycles represents the standard of care 1. The ABVD regimen consists of:

• Doxorubicin (Adriamycin): Cardiotoxicity (dose-dependent cardiomyopathy, arrhythmias), nausea/vomiting, alopecia, myelosuppression 1
• Bleomycin: Pulmonary toxicity (pneumonitis, pulmonary fibrosis - most concerning), fever, skin hyperpigmentation, mucositis 1
• Vinblastine: Peripheral neuropathy, myelosuppression (particularly neutropenia), constipation 1
• Dacarbazine: Nausea/vomiting, myelosuppression, flu-like symptoms 1

PET-Adapted Treatment Strategy

After 2 cycles of ABVD, interim PET-CT should be performed to guide subsequent therapy 1:

• If PET-negative (Deauville score 1-3): Consider omitting bleomycin for cycles 3-6 to reduce pulmonary toxicity risk, especially in elderly patients or those at increased risk for lung toxicity 1
• If PET-positive after 2 cycles: Switch from ABVD to escalated BEACOPP (BEACOPPesc) for improved disease control 1

Alternative Regimen: Escalated BEACOPP

BEACOPPesc (4-6 cycles) is an alternative first-line option for patients ≤60 years who are candidates for more intensive therapy 1. This regimen should NOT be used in patients >60 years due to excessive toxicity 1.

The BEACOPPesc regimen includes:

• Bleomycin (10 mg/m² IV day 8): Pulmonary toxicity 1
• Etoposide (200 mg/m² IV days 1-3): Myelosuppression, secondary leukemia risk 1
• Doxorubicin (35 mg/m² IV day 1): Cardiotoxicity 1
• Cyclophosphamide (1250 mg/m² IV day 1): Hemorrhagic cystitis, infertility, secondary malignancies 1
• Vincristine (1.4 mg/m² IV day 8): Peripheral neuropathy 1
• Procarbazine (100 mg/m² PO days 1-7): Myelosuppression, infertility, secondary malignancies 1
• Prednisone (40 mg/m² PO days 1-14): Hyperglycemia, weight gain, mood changes, immunosuppression 1
• G-CSF (from day 8): Required to manage severe myelosuppression 1

PET-Adapted BEACOPP Strategy

After 2 cycles of BEACOPPesc, PET-negative patients can safely receive only 2 more cycles (total 4), while PET-positive patients require 4 more cycles (total 6) 1.

Radiotherapy Considerations

Radiotherapy is NOT routinely given after chemotherapy for advanced-stage disease 1. RT should be restricted to:

• Patients with PET-positive residual lymphoma ≥2.5 cm after completing 4-6 cycles of BEACOPPesc 1
• Dose: 30 Gy involved-site radiotherapy (ISRT) 1

Special Population: Patients >60 Years

ABVD-based chemotherapy represents the standard of care for older patients fit enough for multi-agent chemotherapy 1. Critical modifications include:

• Bleomycin should be discontinued after cycle 2 to minimize pulmonary toxicity risk 1
• BEACOPP regimen should NOT be given due to unacceptable toxicity 1

Key Toxicity Monitoring

Pulmonary Function

• Bleomycin carries the highest risk of life-threatening pulmonary toxicity 1
• Baseline pulmonary function tests should be obtained before treatment 1
• Discontinue bleomycin immediately if pulmonary symptoms develop 1

Cardiac Function

• Doxorubicin causes cumulative dose-dependent cardiotoxicity 1
• Baseline cardiac function assessment is mandatory 1

Fertility Preservation

• Reproductive counseling and consideration of sperm banking or oocyte/ovarian tissue cryopreservation should be offered before treatment 1
• BEACOPP carries significantly higher infertility risk than ABVD 1

Common Pitfalls to Avoid

• Do not continue bleomycin beyond 2 cycles in patients >60 years - this significantly increases fatal pulmonary toxicity risk 1
• Do not use BEACOPP in patients >60 years - mortality from treatment toxicity outweighs any benefit 1
• Do not routinely add radiotherapy - it is only indicated for specific PET-positive residual disease 1
• Do not skip interim PET-CT - this is essential for treatment adaptation and avoiding unnecessary toxicity 1