Brentuximab vedotin regimen lowers relapse risk in pediatric high-risk Hodgkin lymphoma
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The addition of first-line brentuximab vedotin to chemotherapy reduced risk for relapse compared with standard treatment among pediatric patients with high-risk Hodgkin lymphoma, according to study results.
The findings, published in The New England Journal of Medicine, additionally showed the brentuximab vedotin (Adcetris, Seagen) regimen to be well tolerated.
Background and methods
“Children and adolescents with high-risk Hodgkin lymphoma need better therapy, as 20% of the population are prone to relapse,” Sharon M. Castellino, MD, MSc, director of Children’s Healthcare of Atlanta’s leukemia and lymphoma program at Aflac Cancer and Blood Disorders Center, professor of pediatrics at Emory University School of Medicine, and research member at Winship Cancer Institute of Emory University, told Healio.
“While the [CD-30]-targeted therapy brentuximab vedotin was being studied in the adult ECHELON-1 trial, that approach was not accessible to patients [aged] younger than 18 years,” Castellino continued. “Through Children’s Oncology Group, we designed the AHOD1331 trial to evaluate the efficacy and safety of brentuximab vedotin in the first randomized trial of a targeted therapy for children and teens with newly diagnosed Hodgkin lymphoma.”
The open-label, multicenter, randomized phase 3 study included 587 patients (median age, 15.6 years; 47% female; 57.6% white) with previously untreated high-risk Hodgkin lymphoma enrolled across 153 institutions.
Researchers assigned patients to five 21-day cycles of brentuximab vedotin plus doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide or standard chemotherapy consisting of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide.
EFS served as the primary endpoint. Secondary endpoints included OS and safety.
Median follow-up was 42.1 months (range, 0.1 to 80.9).
Findings
Results showed 3-year EFS rates of 92.1% (95% CI, 88.4-94.7) with the brentuximab vedotin regimen compared with 82.5% (95% CI, 77.4-86.5) with standard treatment (HR = 0.41; 95% CI, 0.25-0.67).
Of note, researchers observed no significant difference in the percentage of patients who underwent involved-site radiation therapy in the brentuximab vedotin regimen group (53.4%) vs. the standard therapy group (56.8%).
Moreover, they observed similar 3-year OS rates with the brentuximab vedotin regimen (99.3%; 95% CI, 97.3-99.8) and standard treatment (98.5%; 95% CI, 96-99.4), as well as similar rates of clinically significant adverse events (73.5% vs. 68.2%).
“The relapse-free survival was 10 percentage points higher than the experience with brentuximab vedotin in the adult cohorts on the ECHELON-1 trial, where brentuximab vedotin was combined with a different backbone of chemotherapy,” Castellino said. “The brentuximab vedotin regimen was well tolerated with minimal level of neuropathy and no differences compared with standard therapy.”
Implications
The results establish a new treatment standard, inclusive of brentuximab vedotin, for advanced-stage and high-risk Hodgkin lymphoma in children, Castellino said.
“It is exciting to have an efficacious and tolerable targeted therapy for children with Hodgkin lymphoma,” she said. “We are now evaluating the incorporation of brentuximab vedotin in children, adolescents and young adults with early-stage favorable and unfavorable Hodgkin lymphoma in a trial led by Children’s Oncology Group, but inclusive of all the National Cancer Trials Network Cooperative Group. We are also hopeful that the data from AHOD1331 will be informative to the application for an FDA indication for brentuximab in children and adolescents with high-risk Hodgkin lymphoma.”
How to reduce radiation therapy for these young patients remains a key question, according to an accompanying editorial by Mark Roschewski, MD, clinical director of the lymphoid malignancies branch of the Center for Cancer Research at NCI, and Catherine M. Bollard, MB, ChB, MD, director of Children’s National Research Institute's Center for Cancer and Immunology Research.
“Future clinical trials should explore strategies to omit radiation therapy altogether in children who have a complete metabolic response, including those with bulky tumors,” they wrote.
References:
- Castellino SM, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2206660.
- Roschewski M, et al. N Engl J Med. 2022;doi:10.1056/NEJMe2211587.
For more information:
Sharon M. Castellino, MD, MSc, can be reached at sharon.castellino@choa.org.
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