On November 10, 2022, the FDA approved brentuximab vedotin (Adcetris; Seagen) in combination with a chemotherapy regimen of doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (AVEPC) for treatment-naïve pediatric patients aged ≥2 years with high-risk classical Hodgkin lymphoma. This is the first indication for brentuximab vedotin for pediatric patients. Brentuximab vedotin has an orphan drug designation for Hodgkin lymphoma.
This drug was previously approved for classical Hodgkin lymphoma in adults, and for adults with various types of anaplastic large-cell lymphoma.
The FDA approval of this new indication was based on results of a randomized, open-label, actively controlled clinical trial. High-risk Hodgkin lymphoma was classified as Ann Arbor stage IIB with bulk disease, stage IIIB, stage IVA, or stage IVB. The total 600 patients were randomized in a 1:1 ratio to brentuximab vedotin plus AVEPC or to a chemotherapy regimen with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). Patients in each arm received up to 5 cycles of the respective drug regimen.
Patients in the brentuximab vedotin plus AVEPC arm received brentuximab vedotin 1.8 mg/kg over 30 minutes (day 1), doxorubicin 25 mg/m2 (days 1 and 2), vincristine 1.4 mg/m2 (day 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 twice daily (days 1-7), and cyclophosphamide 600 mg/m2 (days 1 and 2). In the ABVE-PC arm, patients received doxorubicin 25 mg/m2 (days 1 and 2), bleomycin 5 units/m2 (day1) and 10 units/m2 (day 8), vincristine 1.4 mg/m2 (days 1 and 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 twice daily (days 1-7), and cyclophosphamide 600 mg/m2 (days 1 and 2).
The main efficacy measure was event-free survival (EFS), defined as the time from randomization to the earliest of disease progression or relapse, second malignancy, or death from any cause. The median EFS was not reached in either arm.
A total of 23 (8%) adverse events occurred in the brentuximab vedotin plus AVEPC arm versus 52 (17%) events in the ABVE-PC arm (hazard ratio, 0.41; 95% confidence interval, 0.25-0.67; P = .0002). The most common (≥5%) grade 3 or 4 adverse events with brentuximab vedotin plus AVEPC in pediatric patients were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.