On 10 November 2022, the US Food and Drug Administration (FDA) approved brentuximab vedotin (Adcetris, Seagen, Inc.) in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for paediatric patients 2 years of age and older with previously untreated high risk classical Hodgkin lymphoma (cHL). This is the first paediatric approval for brentuximab vedotin.
Efficacy was evaluated in a randomised, open-label, actively controlled study. High risk was identified as Ann Arbor Stage IIB with bulk disease, Stage IIIB, Stage IVA, and Stage IVB. Of the 600 total patients randomised, 300 were randomised to brentuximab vedotin plus doxorubicin (A), vincristine (V), etoposide (E), prednisone (P), and cyclophosphamide (C) [brentuximab vedotin + AVEPC], and 300 patients were randomised to A+bleomycin (B)+V+E+P+C [ABVE-PC] arm. Patients in each treatment arm received up to 5 cycles of the following:
- 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 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2); or
- ABVE-PC arm: 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 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2).
The main efficacy outcome measure was event-free survival (EFS), defined as the time from randomisation to the earliest of disease progression or relapse, second malignancy, or death due to any cause. Median EFS was not reached in either arm. There were 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% confidence interval 0.25, 0.67; p = 0.0002).
The most common Grade ≥3 adverse reactions (≥5%) in paediatric patients treated with brentuximab vedotin in combination with AVEPC were neutropenia, anaemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.
The recommended brentuximab vedotin dose for paediatric patients 2 years of age and older is 1.8 mg/kg up to a maximum of 180 mg in combination with AVEPC every 3 weeks for a maximum of 5 doses.
Full prescribing information for Adcetris is available here.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. 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.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.
