What were the design, dosing schedule, and outcomes of the phase I/II trial of brentuximab vedotin (BV) combined with ifosfamide, carboplatin, and etoposide (ICE) administered every three weeks in adult patients with relapsed or refractory classical Hodgkin lymphoma after prior therapy?

BV-ICE Regimen: Study Design and Outcomes

Phase I/II Trial Design

The BV-ICE combination was evaluated in a phase I/II study where brentuximab vedotin (1.8 mg/kg) was administered on day 1 of each 21-day cycle combined with standard ICE chemotherapy (ifosfamide, carboplatin, and etoposide) for 2 cycles in patients with relapsed or refractory classical Hodgkin lymphoma. 1

Study Population and Dosing Schedule

• The phase I portion enrolled 10 patients to determine the maximum tolerated dose, finding no dose-limiting toxicities and establishing BV 1.8 mg/kg as the recommended phase II dose 1
• The phase II portion enrolled 42 patients with relapsed/refractory classical Hodgkin lymphoma after prior therapy 1
• BV was administered at 1.8 mg/kg intravenously on day 1 of each 21-day cycle 1
• ICE chemotherapy was given on days 1-3 using standard dosing 1
• Patients received 2 cycles of BV-ICE before response assessment 1

Primary Outcomes

• Complete metabolic response (CMR) rate after 2 cycles was 61.9% (26 of 42 patients), which was the primary endpoint 1
• Overall response rate reached 88% when including partial responses 1
• 88% of patients (37 of 42) successfully proceeded to autologous stem cell transplantation 1

Long-Term Survival Data

• With median follow-up of 38 months, the 3-year progression-free survival was 64.3% 1
• The 3-year overall survival rate was 100%, indicating no deaths occurred during this follow-up period 1

Safety Profile

Hematologic Toxicity

• Hematological toxicities occurred in 81% of patients and were the most frequent adverse events 1
• Grade 3-4 neutropenia occurred in 73% of patients 1
• Grade 3-4 thrombocytopenia occurred in 80% of patients 1

Non-Hematologic Toxicity

• Infections occurred in 21% of patients 1
• Febrile neutropenia occurred in 9% of patients 1
• Sepsis occurred in 13% of patients 1
• One treatment-related death (2%) occurred due to multisystem organ failure 1

Alternative Dosing Schedule: Dose-Dense BV-ICE

A separate phase I/II study evaluated a dose-dense schedule where BV was administered on both days 1 and 8 of each 21-day cycle at either 1.2 mg/kg or 1.5 mg/kg, with the recommended phase 2 dose established at 1.5 mg/kg 2. This dose-dense approach achieved a 74% complete response rate after two cycles in 43 evaluable patients 2.

Clinical Context from Guidelines

Position in Treatment Algorithm

• NCCN guidelines recognize ICE as one of the most commonly used salvage regimens for relapsed/refractory Hodgkin lymphoma before high-dose therapy and autologous stem cell transplant 3
• Multiple studies have investigated incorporating brentuximab vedotin into initial salvage therapy to increase complete response rates before transplant 3
• The combination approach aims to achieve higher rates of PET-negative responses, which is the most important predictor of post-transplant outcomes 3

Comparison to Other BV Combinations

• BV-ICE demonstrated similar or superior activity compared to other BV-containing salvage regimens (BV-DHAP, BV-bendamustine, BV-ESHAP) that achieved PET-negative response rates of 75-90% 3
• The advantage of BV-ICE is rapid administration over just 2 cycles compared to longer durations required for other combinations 2