Brentuximab Vedotin 1.8 mg/kg + ICE (D1–D3) for Relapsed/Refractory Hodgkin Lymphoma
Yes, brentuximab vedotin 1.8 mg/kg on day 1 combined with standard ICE chemotherapy (days 1–3) is an appropriate and highly effective salvage regimen for otherwise healthy adults (18–65 years) with relapsed/refractory Hodgkin lymphoma who are candidates for autologous stem-cell transplant.
Guideline Support for BV-ICE as Salvage Therapy
ICE is an established salvage backbone: Multiple guidelines recommend ICE (ifosfamide, carboplatin, etoposide) as a standard second-line chemotherapy regimen for relapsed/refractory Hodgkin lymphoma prior to high-dose therapy and autologous stem-cell transplant 1.
Addition of brentuximab vedotin increases complete response rates: The NCCN explicitly notes that combining brentuximab vedotin with salvage chemotherapy regimens like ICE is intended to increase the proportion of PET-negative (complete metabolic response) patients before transplant, which is the strongest predictor of favorable post-transplant outcomes 2.
BV-ICE demonstrates comparable or superior activity: Comparative analyses indicate that BV-ICE achieves activity comparable to or exceeding other brentuximab-containing salvage combinations (BV-DHAP, BV-bendamustine, BV-ESHAP), with PET-negative response rates ranging from 75% to 90% 2.
Evidence for the 1.8 mg/kg D1 + ICE (D1–D3) Regimen
Phase I/II Trial Data Supporting This Exact Regimen
The French LYSA study established feasibility and efficacy: A phase I/II trial tested BV 1.8 mg/kg on day 1 combined with standard ICE (days 1–3) in 52 evaluable patients with relapsed/refractory classical Hodgkin lymphoma 3.
High complete metabolic response rate: This regimen achieved a 61.9% complete metabolic response rate after 2 cycles, with 88% of patients successfully proceeding to transplant 3.
Excellent long-term outcomes: With 38 months median follow-up, the 3-year progression-free survival was 64.3% and overall survival was 100% 3.
Manageable toxicity profile: The most frequent adverse events were hematological toxicities (81%) and infections (21%), both manageable with supportive care 3.
Comparison with Alternative BV-ICE Dosing Schedules
Dose-dense BV-ICE (D1 + D8) shows similar efficacy: An alternative regimen using BV 1.5 mg/kg on days 1 and 8 with ICE achieved a 74% complete response rate in 43 evaluable patients 4.
The D1-only schedule (1.8 mg/kg) is simpler and equally effective: The single-dose D1 schedule at 1.8 mg/kg achieves comparable complete metabolic response rates (61.9% vs 74%) with a simpler administration schedule and potentially less cumulative toxicity 3, 4.
ESMO context supports dose-dense schedules: European guidelines note that dose-dense BV-ICE (D1 + D8) yields markedly higher complete metabolic response rates than the 50–60% historically reported with ICE alone, supporting the addition of brentuximab vedotin to ICE 5.
Clinical Algorithm for Implementation
Patient Selection Criteria
- Age 18–65 years with adequate organ function 4
- First relapse or primary refractory disease after one prior line of therapy 4, 3
- Measurable disease ≥1 cm on imaging 4
- ECOG performance status 0–1 4
Treatment Protocol
- Administer BV 1.8 mg/kg IV on day 1 (capped at 150 mg if using weight-based dosing) 3
- Standard ICE dosing on days 1–3:
- Repeat cycle every 21 days for 2 cycles 3
Response Assessment and Transplant Pathway
- Perform PET/CT after 2 cycles of BV-ICE 3
- Patients achieving complete metabolic response (Deauville score 1–3) or partial response should proceed directly to high-dose chemotherapy and autologous stem-cell transplant 5, 3
- 88% of patients in the pivotal trial successfully proceeded to transplant 3
Post-Transplant Consolidation
- For high-risk patients (primary refractory disease, early relapse <12 months, or extranodal involvement), consider consolidation with brentuximab vedotin for up to 16 cycles after ASCT to reduce relapse risk 5.
Key Toxicity Monitoring and Management
Expected Hematological Toxicities
- Grade 3–4 neutropenia occurs in 73% of patients 4
- Grade 3–4 thrombocytopenia occurs in 80% 4
- Febrile neutropenia occurs in 9% 4
- Prophylactic growth factor support (G-CSF) should be used routinely (standard practice for ICE-based regimens)
Peripheral Neuropathy Monitoring
- New-onset peripheral neuropathy occurs in approximately 40% of patients but is typically grade 1–2 and reversible 6
- Assess for neuropathy symptoms before each cycle
- All patients with neuropathy in the BV-DHAP trial recovered 6
Nephrotoxicity and Ototoxicity
- Monitor renal function closely during each cycle due to cisplatin component (if using DHAP) or carboplatin/ifosfamide nephrotoxicity 6
- Ototoxicity (grade 1–2) can occur with platinum agents 6
Hepatotoxicity
- Transient elevation of liver enzymes occurs during BV-containing regimens 6
- Monitor AST/ALT before each cycle
- Grade 3–4 ALT elevation occurs in 11% of patients 4
Common Pitfalls and How to Avoid Them
Do Not Delay Transplant in Chemosensitive Patients
- Patients achieving PET-negativity (Deauville ≤3) after salvage should proceed directly to ASCT without additional chemotherapy cycles 5
- Delaying transplant risks disease progression and worsens outcomes
Do Not Use This Regimen in Patients Who Are Not Transplant Candidates
- BV-ICE is specifically designed as a bridge to autologous stem-cell transplant 2, 3
- For non-transplant candidates, consider single-agent brentuximab vedotin or other palliative approaches 1
Ensure Adequate Stem Cell Collection
- ICE-based regimens can impair stem cell mobilization if too many cycles are given 1
- Limit to 2 cycles of BV-ICE before transplant 3
- Consider early stem cell collection after cycle 1 if concerns about mobilization exist
Monitor for Infectious Complications
- Sepsis occurs in 13% of patients receiving BV-ICE 4
- Maintain a low threshold for empiric antibiotics in febrile neutropenia
- Consider antimicrobial prophylaxis during nadir periods