On November 10, 2022, the U.S. Food and Drug Administration (FDA) approved brentuximab vedotin (Adcetris®) plus doxorubicin (A), vincristine (V), etoposide (E), prednisone (P), and cyclophosphamide (C) [brentuximab vedotin + AVEPC] for pediatric patients aged two years and older with previously untreated, high-risk classical Hodgkin lymphoma. This is the first pediatric approval for brentuximab vedotin.
Efficacy was evaluated in a randomized, open-label, active control trial. High risk was identified as Ann Arbor stage IIB with bulk disease, stage IIIB, stage IVA, and stage IVB. Of the 600 total patients, 300 were randomized to receive brentuximab vedotin + AVEPC and 300 were randomized to receive A+bleomycin (B)+V+E+P+C [ABVE-PC] arm. Each treatment arm received up to five cycles administered as:
- Brentuximab vedotin + AVEPC arm: 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 bis in die (days 1–7), and cyclophosphamide 600 mg/m2 (days 1 and 2)
- ABVE-PC arm: doxorubicin 25 mg/m2 (days 1 and 2), bleomycin 5 units/m2 (day 1) 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 bis in die (days 1–7), and cyclophosphamide 600 mg/m2 (days 1 and 2)
The main efficacy outcome measure was event-free survival (EFS), defined as time from randomization to the earliest time that patients experienced disease progression or relapse, second malignancy, or death from any cause. Median EFS was not reached in either arm. Patients experienced 23 events (8%) in the brentuximab vedotin + AVEPC arm and 52 events (17%) in the ABVE-PC arm, with a corresponding hazard ratio of 0.41 (95% CI = 0.25, 0.67; p = 0.0002).
The most common grade 3 or higher adverse events reported in at least 5% of pediatric patients treated with brentuximab vedotin + AVEPC were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.
The recommended brentuximab vedotin dose for pediatric patients aged two years and older is 1.8 mg/kg up to a maximum of 180 mg in combination with AVEPC every three weeks for a maximum of five doses.
View the full prescribing information for brentuximab vedotin.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
The application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Brentuximab vedotin has orphan drug designation for the treatment of Hodgkin lymphoma.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.