FDA Approves Brentuximab Vedotin Plus Chemotherapy for Pediatric Patients With Classical Hodgkin Lymphoma

On November 10, 2022, the Food and Drug Administration (FDA) approved brentuximab vedotin in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for pediatric patients 2 years of age and older with previously untreated high-risk classical Hodgkin lymphoma. Notably, this was the first pediatric approval for brentuximab vedotin.

The efficacy of this combination was demonstrated in a randomized, open-label, actively controlled trial that included 600 total patients. Patients were randomized in a 1:1 ratio to receive brentuximab vedotin combined with either doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (AVEPC; n = 300) or doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC; n = 300).

Patients in brentuximab vedotin plus AVEPC arm received up to 5 cycles of brentuximab vedotin 1.8 mg/kg over 30 minutes on day 1, doxorubicin 25 mg/m² on days 1 and 2, vincristine 1.4 mg/m²  on day 8, etoposide 125 mg/m² on days 1 to 3, prednisone 20 mg/m² BID on days 1 to 7,  and cyclophosphamide 600 mg/m² on days 1 and 2. Patients in the ABVE-PC arm received up to 5 cycles of  doxorubicin 25 mg/m²  on days 1 and 2, bleomycin 5 units/m²  on day 1 and 10 units/m² on day 8, vincristine 1.4 mg/m² on days 1 and 8, etoposide 125 mg/m² on days 1 to 3, prednisone 20 mg/m² BID on days 1 to 7, and cyclophosphamide 600 mg/m² on days 1 and 2.

In the trial, the main efficacy outcome measure was event-free survival (EFS), defined as the time from randomization 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 plus AVEPC arm and 52 events (17%) in the ABVE-PC arm with a corresponding hazard ratio of 0.41 (95% confidence interval, 0.25 to 0.67; P = .0002).

Among the pediatric patients on the trial, the most common grade ≥3 adverse reactions (≥5%) associated with brentuximab vedotin plus AVEPC were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection.

 Source:

FDA approves brentuximab vedotin in combination with chemotherapy for pediatric patients with classical Hodgkin lymphoma. Press Release. The US Food and Drug Administration. Published online November 10, 2022. Accessed November 16, 2022. http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-combination-chemotherapy-pediatric-patients-classical-hodgkin