BV-ICE Dosing Regimen for Relapsed/Refractory Hodgkin Lymphoma
The D1+D8 dosing schedule (dose-dense BV-ICE) is the superior regimen, delivering brentuximab vedotin at 1.5 mg/kg on days 1 and 8 with standard ICE chemotherapy on days 1-3, repeated every 21 days for two cycles. 1
Evidence Supporting D1+D8 Dosing
The most recent and highest-quality evidence comes from a phase 1/2 trial that specifically compared dose levels and established the recommended phase 2 dose at 1.5 mg/kg given on both day 1 and day 8 1. This dose-dense approach achieved:
- Complete response rate of 74% (95% CI 58.8-86.5) after two cycles 1
- Rapid administration with only two 21-day cycles needed before proceeding to autologous stem cell transplant 1
- Activity comparable to or exceeding other BV-containing salvage regimens that require much longer treatment durations 1
The dose-dense schedule was specifically designed to maximize drug exposure while maintaining tolerability, with the phase 1 portion establishing that 1.5 mg/kg on days 1 and 8 was the maximum tolerated dose 1.
Comparison to Alternative Dosing
The sequential approach (BV alone followed by ICE for non-responders) achieved a 76% CR rate but required PET-adapted therapy and longer treatment duration 2. While this sequential strategy showed 27% achieved PET-negativity with BV alone, the remaining 73% required additional augmented ICE chemotherapy 2. This approach is more complex and time-consuming compared to the integrated dose-dense regimen.
The NCCN guidelines note that combining BV with salvage chemotherapy increases complete metabolic response rates, which is the strongest predictor of favorable post-transplant outcomes 3. Multiple BV-containing combinations achieve PET-negative response rates of 75-90%, and the dose-dense BV-ICE regimen falls within this range 3.
Practical Implementation
Dosing schedule:
- Brentuximab vedotin 1.5 mg/kg IV (capped at 150 mg) on days 1 and 8 1
- Ifosfamide 5 g/m² plus mesna 5 g/m² IV over 24 hours on day 2 1
- Carboplatin AUC 5 IV on day 2 1
- Etoposide 100 mg/m² IV on days 1-3 1
- Repeat cycle every 21 days for two cycles 1
Toxicity Profile
Expected hematologic toxicities:
- Grade 3-4 neutropenia in 73% of patients 1
- Grade 3-4 thrombocytopenia in 80% of patients 1
- Grade 3-4 anemia in 13% of patients 1
Non-hematologic toxicities:
Serious adverse events occurred in 29% of patients, with one treatment-related death (2%) from multisystem organ failure 1. These toxicity rates are manageable in transplant-eligible patients under age 60 years 1.
Clinical Context
This regimen is appropriate for patients with first relapse or primary refractory classical Hodgkin lymphoma after one prior line of therapy who are fit for intensive chemotherapy and autologous stem cell transplant 1. The goal is achieving PET-negativity before transplant, which dramatically impacts post-transplant outcomes 4. All 44 patients who completed the dose-dense BV-ICE protocol as planned proceeded successfully to transplant 1.
The dose-dense approach offers the advantage of rapid disease control with only 6 weeks of treatment before stem cell collection and transplant, compared to longer sequential strategies 1, 2.