On November 10, 2022, brentuximab vedotin was approved for use in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for pediatric patients aged ≥ 2 years with previously untreated high-risk classical Hodgkin lymphoma.1
Supporting Efficacy Data
Approval was supported by findings in the open-label phase III Children’s Oncology Group AHOD1331 trial (ClinicalTrials.gov identifier NCT02166463). A total of 600 patients were randomly assigned to receive brentuximab vedotin at 1.8 mg/kg every 3 weeks plus AVEPC chemotherapy (n = 300; doxorubicin, vincristine, etoposide, prednisone, cyclophosphamide) or chemotherapy with bleomycin and AVEPC (ABVE-PC group, n = 300) given in up to five 21-day cycles. High risk was identified as Ann Arbor stage IIB with bulky disease and stage IIIB, IVA, or IVB disease.
Median event-free survival was not reached in either group. Event-free survival events occurred in 23 patients (8%) in the brentuximab vedotin group vs 52 patients in the chemotherapy group (hazard ratio [HR] = 0.41, 95% confidence interval = 0.25–0.67, P = .0002).
How It Is Used
The recommended brentuximab vedotin dose for pediatric patients aged ≥ 2 years is 1.8 mg/kg intravenously up to a maximum of 180 mg in combination with AVEPC every 3 weeks for a maximum of five doses. Product labeling provides instructions for dosage modifications for adverse reactions including peripheral neuropathy and neutropenia.
Safety Profile
The most common adverse events of any grade (≥ 20%) in any brentuximab vedotin study have been peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.
OF NOTE
Brentuximab vedotin has warnings/precautions for peripheral neuropathy, anaphylaxis and infusion reactions, hematologic toxicities, serious infections and opportunistic infections, tumor-lysis syndrome, hepatotoxicity, pulmonary toxicity, serious dermatologic reactions, gastrointestinal complications, hyperglycemia, and embryofetal toxicity.
In the AHOD1331 trial, the most common grade 3 or 4 adverse events (≥ 5%) in patients receiving brentuximab vedotin plus AVEPC were neutropenia (51% vs 40% in the ABVE-PC group), anemia (37% vs 30%), thrombocytopenia (32% vs 27%), febrile neutropenia (31% vs 33%), lymphopenia (24% vs 26%), infections (12% vs 10%), stomatitis (10% vs 7%), peripheral sensory neuropathy (6% vs 4%), and hypokalemia (6% vs 7%). Serious adverse events in the brentuximab vedotin group included hypotension (3%) and febrile neutropenia (3%).
Concomitant use of brentuximab vedotin with bleomycin is contraindicated because of the risk of pulmonary toxicity. Brentuximab vedotin has warnings/precautions for peripheral neuropathy, anaphylaxis and infusion reactions, hematologic toxicities, serious infections and opportunistic infections, tumor-lysis syndrome, hepatotoxicity, pulmonary toxicity, serious dermatologic reactions, gastrointestinal complications, hyperglycemia, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving brentuximab vedotin.
REFERENCE
1. Adcetris (brentuximab vedotin) for injection, for intravenous use, prescribing information, Seagen Inc, November 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125388s106lbl.pdf. Accessed December 7, 2022.
