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Addition of Brentuximab Vedotin to Chemotherapy in Pediatric High-Risk Hodgkin Lymphoma


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As reported in The New England Journal of Medicine by Castellino et al, the phase III Children’s Oncology Group (COG) AHOD1331 trial showed improved event-free survival with brentuximab vedotin plus chemotherapy vs standard chemotherapy in previously untreated pediatric patients with high-risk Hodgkin lymphoma.

Study Details

In the open-label multicenter trial, 587 patients aged 2 to 21 years with stage IIB with bulky tumor, IIIB, IVA, or IVB disease were enrolled at COG institutions in North America between March 2015 and August 2019. Patients were randomly assigned to receive five 21-day cycles of brentuximab vedotin at 1.8 mg/kg plus doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (n = 298) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group, n = 289), with granulocyte colony–stimulating factor support received in both groups. Patients were assessed with positron-emission tomography/computed tomography (PET-CT) after two cycles. Slow-responding lesions on PET-CT and large mediastinal adenopathy present at baseline were treated with involved-field radiation therapy after cycle 5. The primary endpoint was event-free survival.

Event-Free Survival

The median age was 15.4 years in the brentuximab vedotin group and 15.8 years in the standard-care group. Approximately 60% of patients in both groups had stage IV disease, and 52.7% and 56.4% had large mediastinal adenopathy, respectively. Involved-field radiation therapy was received by 53.4% and 56.8% of patients. 

KEY POINTS

  • Brentuximab vedotin plus chemotherapy significantly improved 3-year event-free survival vs standard chemotherapy alone.
  • A particular benefit with brentuximab vedotin plus chemotherapy over chemotherapy alone was observed among patients with slow-responding lesions on interim PET-CT.

Median follow-up was 42.1 months (range = 0.1–80.9 months). Event-free survival at 3 years was 92.1% (95% confidence interval [CI] = 88.4%–94.7%) in the brentuximab vedotin group vs 82.5% (95% CI = 77.4%–86.5%) in the standard-care group (hazard ratio [HR] = 0.41, 95% CI = 0.25–0.67, P < .001).

In a post hoc analysis, 3-year event free survival was 90.7% vs 68.3% among 55 vs 55 patients with slow-responding lesions on interim PET-CT (HR = 0.28, 95% CI = 0.10–0.76). Among patients with rapid-responding lesions, 3-year event-free survival was 92.3% vs 85.7% (HR = 0.48, 95% CI = 0.27–0.84).

The cumulative incidence of relapse was 7.5% (95% CI = 4.9%–10.9%) vs 17.1% (95% CI = 12.9%–21.8%). Overall survival at 3 years was 99.3% (95% CI = 97.3%–99.8%) vs 98.5% (95% CI = 96.0%–99.4%).

Adverse Events

Grade ≥ 3 adverse events occurred in 73.5% of patients in the brentuximab vedotin group vs 68.2% of the standard-care group; the most common events in both groups included febrile neutropenia (30.9% vs 32.5%), mucositis/oral adverse events (10.4% vs 7.3%), and peripheral neuropathy (6.7% vs 5.5%). Sepsis occurred in 2.7% vs 4.2% of patients; thromboembolic events occurred in 3.7% vs 1.7%. Grade ≥ 2 peripheral neuropathy occurred in 18.8% vs 19.4%. No cases of pneumonitis were observed in the brentuximab vedotin group. No deaths occurred during study treatment.

The investigators concluded, “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.”

Sharon M. Castellino, MD, of the Department of Pediatrics, Emory University School of Medicine, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by the National Institutes of Health and others. For full disclosures of the study authors, visit nejm.org.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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