Literature
Clinical Pearls & Morning Reports
Published November 2, 2022
How did brentuximab vedotin combined with multiagent chemotherapy compare with standard care in the trial by Castellino et al.?
Castellino et al. conducted an open-label, phase 3 trial comparing a regimen of brentuximab vedotin plus doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide with the standard bleomycin-containing chemotherapy regimen in children and adolescents with high-risk classic Hodgkin’s lymphoma. Read the NEJM Original Article here.
Clinical Pearls
Q: Do children and adults with advanced-stage Hodgkin’s lymphoma receive similar chemotherapy regimens?
A: In contrast to the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) that is used in adults with Hodgkin’s lymphoma, regimens in children with advanced-stage disease include etoposide and cyclophosphamide with continued use of glucocorticoids, while limiting cumulative doses of doxorubicin and bleomycin.
Q: How often does the current combination chemotherapy for pediatric high-risk Hodgkin’s lymphoma result in sustained disease control?
A: Despite greater disease control with pediatric approaches, contemporary combination therapy has not resulted in sustained disease control with initial therapy in 15 to 25% of children and adolescents with Hodgkin’s lymphoma. This situation necessitates additional therapies that have been associated with late effects, including second cancers, infertility, and cardiovascular disease and with subsequently reduced overall survival.
Morning Report Questions
Q: How did brentuximab vedotin combined with multiagent chemotherapy compare with standard care in the trial by Castellino et al.?
A: In this phase 3, randomized trial of the CD30-targeted antibody–drug conjugate brentuximab vedotin in children, the authors found superior event-free survival (the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died) with the brentuximab vedotin–based regimen in a large, representative, racially and ethnically diverse cohort of patients in North America. The addition of brentuximab vedotin to chemotherapy resulted in a 9.6-percentage-point improvement in 3-year event-free survival as compared with conventional chemotherapy alone. Separation of the event curves occurred early, with a plateau in the cumulative incidence of relapse events in the brentuximab vedotin group by 2 years after diagnosis.
Q: What were some additional results of the trial by Castellino et al.?
A: The cumulative incidence of relapse was lower in the brentuximab vedotin group (7.5%; 95% CI, 4.9 to 10.9) than in the standard-care group (17.1%; 95% CI, 12.9 to 21.8). The 3-year overall survival was 99.3% (95% CI, 97.3 to 99.8) in the brentuximab vedotin group and 98.5% (95% CI, 96.0 to 99.4) in the standard-care group. The overall incidence of clinically significant adverse events was similar in the two groups (73.5% with the brentuximab vedotin–based regimen and 68.2% with the standard regimen). Febrile neutropenia was reported in 30.9% of the patients who received the brentuximab vedotin–based regimen and in 32.5% of those who received the standard regimen.