Targeted Therapy with Brentuximab Vedotin Reduces Relapse Risk in Pediatric Patients with High-Risk Hodgkin Lymphoma

TON - December 2022 Vol 15, No 6

Standard pediatric chemotherapy regimens used in the treatment of children and adolescents with high-risk Hodgkin lymphoma are often associated with late effects, including second cancers, infertility, and cardiovascular disease, as well as significantly reduced overall survival (OS). According to published results from a phase 3, prospective, multicenter, randomized clinical trial, the addition of the CD-30–targeted antibody–drug conjugate brentuximab vedotin (Adcetris) to standard chemotherapy can reduce the risk for relapse in this population of patients while providing a better tolerability profile (Castellino SM, et al. N Engl J Med. 2022;387:1649-1660).

Study Details

The AHOD1331 trial included 587 patients aged 2 to 21 years with newly diagnosed, high-risk classic Hodgkin lymphoma enrolled across 153 Children’s Oncology Group institutions. Patients were randomized in a 1:1 ratio to five 21-day cycles of brentuximab vedotin plus doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide or the standard pediatric chemotherapy regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Both arms received involved-site radiation therapy based on responses assessed via 18F-fluorodeoxyglucose–positron-emission tomography and computed tomography after 2 cycles of treatment.

The primary end point of the study was event-free survival (EFS), defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Secondary end points included OS and safety. Patient and disease characteristics were balanced across the treatment arms.


At a median follow-up of 42.1 months, 3-year EFS rates were 92.1% (95% confidence interval [CI], 88.4-94.7) in the brentuximab vedotin arm compared with 82.5% (95% CI, 77.4-86.5) in the standard treatment arm, indicating that the risk for an event or death was 9.6 percentage points lower with brentuximab vedotin therapy than with standard treatment (P <.001 by a 2-sided log-rank test).

The cumulative incidence of relapse was lower in the brentuximab vedotin arm (7.5%; 95% CI, 4.9-10.9) than in the standard treatment arm (17.1%; 95% CI, 12.9-21.8).

In addition, the researchers reported similar 3-year OS rates in patients treated with the brentuximab vedotin regimen (99.3%; 95% CI, 97.3-99.8) compared with those treated with the standard regimen (98.5%; 95% CI, 96-99.4), as well as similar rates of clinically significant adverse events (73.5% vs 68.2%, respectively).

Moreover, there was no significant difference observed in the percentage of patients who underwent involved-site radiation therapy in the brentuximab vedotin arm versus the standard therapy arm (53.4% vs 56.8%, respectively).

“The addition of brentuximab vedotin to standard chemotherapy resulted in superior efficacy, with a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years,” concluded Sharon M. Castellino, MD, MSc, Director, Leukemia and Lymphoma, Children’s Healthcare of Atlanta, Emory University, GA, and colleagues. “Long-term follow-up will be important to more thoroughly assess the occurrence of late events and overall survival.”

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