What is the treatment approach for relapsed/refractory Hodgkin lymphoma or anaplastic large cell lymphoma with Brentuximab (Adcetris)?

Brentuximab Vedotin for Relapsed/Refractory Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma

Brentuximab vedotin is FDA-approved and NCCN-recommended for relapsed/refractory CD30+ Hodgkin lymphoma after autologous stem cell transplant (ASCT) failure or after at least 2 prior chemotherapy regimens when ASCT is not an option, achieving 75% overall response rates with durable remissions in complete responders. 1

FDA-Approved Indications and Dosing

Standard dosing is 1.8 mg/kg intravenously over 30 minutes every 3 weeks for up to 16 cycles. 2

For Hodgkin Lymphoma:

• Post-ASCT failure: Approved after autologous stem cell transplant failure 1
• Non-transplant candidates: Approved after at least 2 prior multiagent chemotherapy regimens when ASCT or multiagent chemotherapy is not a treatment option 1

For Anaplastic Large Cell Lymphoma:

• Approved for systemic ALCL (both ALK+ and ALK-) after failure of at least one prior multiagent chemotherapy regimen 3, 2
• For ALK+ ALCL specifically: 81% overall response rate with 69% complete response rate, with 5-year OS and PFS rates of 56% and 37% respectively 3

Clinical Efficacy Data

Hodgkin Lymphoma Post-ASCT:

• Overall response rate: 75% (34% complete remission) 1
• Median PFS: 5.6 months for all patients; 20.5 months for complete responders 1
• 3-year outcomes: Median OS 40.5 months, median PFS 9.3 months 1
• For complete responders: 3-year OS 73%, 3-year PFS 58% 1

Pre-ASCT Salvage Setting:

• Overall response rate: 69% (33% complete remission) 1
• 90% of evaluable patients successfully proceeded to ASCT 1
• Response rates: 75% for primary refractory disease, 66% for relapsed disease 1

Systemic ALCL:

• Overall response rate: 86% (59% complete remission) 2

Treatment Algorithm by Clinical Scenario

Scenario 1: Post-ASCT Relapse

1. Confirm relapse with biopsy 1
2. Initiate brentuximab vedotin 1.8 mg/kg IV every 3 weeks 1, 2
3. Continue for up to 16 cycles or until disease progression 2
4. For complete responders: Consider allogeneic transplant consolidation (2-year PFS 66%) 4

Scenario 2: Relapsed/Refractory Pre-ASCT

1. Use brentuximab vedotin as second-line therapy option 1
2. Can be given as single agent or combined with bendamustine (78% overall response rate with combination) 5
3. Perform PET assessment after 2 cycles 1
4. If Deauville score 1-3: Proceed to ASCT 1
5. If Deauville score 4-5: Consider additional therapy or proceed to ASCT if score 4 1

Scenario 3: Post-ASCT Consolidation (High-Risk Patients)

Administer brentuximab vedotin maintenance for 1 year after ASCT in patients with: 1

• Primary refractory disease
• Relapse <12 months after frontline therapy
• Relapse ≥12 months with extranodal disease

AETHERA trial results supporting this approach: 1

• Median PFS: 42.9 months (brentuximab) vs 24.1 months (placebo)
• 2-year PFS: 65% vs 45%

Scenario 4: Retreatment After Prior Brentuximab Response

Retreatment is effective in patients who achieved CR/PR with initial brentuximab therapy: 6

• Overall response rate: 60% in HL (30% CR), 88% in ALCL (63% CR)
• Median duration of response: 9.5 months
• 45% of complete responders had response durations >1 year

Combination Strategies

Brentuximab + Bendamustine:

For heavily pretreated patients, the combination achieves superior responses: 5

• Overall response rate: 78%
• Recommended doses: Brentuximab 1.8 mg/kg + bendamustine 90 mg/m² (days 1 and 2)
• This serves as an alternative to platinum-based chemotherapy before ASCT 5

Safety Profile and Monitoring

Most Common Adverse Events:

• Peripheral sensory neuropathy: 36-57% (most common, typically reversible) 1, 3
• Neutropenia: 24-25% 1
• Upper respiratory tract infection: 25% 1
• Fatigue: 21% 1

Critical Monitoring Requirements:

• Monitor for peripheral neuropathy at each visit; dose reduce or delay if grade 2-3 develops 3
• Monitor for progressive multifocal leukoencephalopathy (PML), though rare 3
• Peripheral motor neuropathy is more common with retreatment 6

Key Clinical Pitfalls to Avoid

Do not use more than 2 lines of salvage chemotherapy before ASCT, as this selects for highly chemoresistant clones. 7

The value of brentuximab consolidation post-ASCT in patients who received prior brentuximab is unknown. 1

Brentuximab can be safely followed by allogeneic transplant without increased toxicity. 4

Achieving PET-negative status should be the goal of salvage therapy regardless of the protocol used. 1