Brentuximab Vedotin Plus AVD vs ABVD for the First-Line Treatment of Early-Stage Unfavorable-Risk Hodgkin Lymphoma

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In a European phase II trial (BREACH) reported in the Journal of Clinical Oncology, Fornecker et al found that brentuximab vedotin (BV) plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) improved the rate of positron-emission tomography (PET)-negative status after two cycles of treatment vs doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) in previously untreated patients with early-stage unfavorable-risk Hodgkin lymphoma.

Study Details

A total of 170 patients aged ≤ 60 years with at least one unfavorable EORTC/LYSA criterion were randomly assigned 2:1 between March 2015 and October 2016 to four cycles of BV-AVD (n = 113) or ABVD (n = 57) followed by involved-node radiotherapy at 30 Gy. Treatment consisted of 28-day cycles of BV-AVD (BV at 1.2 mg/kg, doxorubicin at 25 mg/m2, vinblastine at 6 mg/m2, and dacarbazine at 375 mg/m2) once daily on days 1 and 15 and ABVD with bleomycin 10 mg/m2 and AVD at the same dose and schedule.

The primary endpoint was PET response after two cycles on independent review. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%.


PET negativity after two cycles was observed in 93 (82.3%, 90% confidence interval [CI] = 75.3%–88.0%) of 113 patients in the BV-AVD group vs 43 (75.4%, 90% CI = 64.3%–84.5%) of 57 in the ABVD group.

At the end of treatment, investigator-assessed complete response was achieved in 98 patients (86.7%, 90% CI = 80.3%–91.6%) in the BV-AVD group vs 45 (78.9%, 90% CI = 68.1%–87.7%) in the ABVD group.


  • PET-negativity was observed in 82.3% of the BV-AVD group vs 75.4% of the ABVD group after two treatment cycles.
  • Complete response was observed in 86.7% vs 78.9% at end of treatment.

Progression-free survival at 2 years was 97.3% (95% CI = 91.9%–99.1%) vs 92.6% (95% CI = 81.4%–97.2%). A total of 33 patients (31%) in the BV-AVD group and 14 (29%) in the ABVD group had high total metabolic tumor volume (> 177 cm3); among these patients, progression-free survival at 2 years was 90.9% (95% CI = 74.4%–97.0%) vs 70.7% (95% CI = 39.4%–87.9%).

Adverse Events

Grade 3 or 4 adverse events occurred in 86% of patients in the BV-AVD group and 69% of the ABVD group, most commonly hematologic events (neutropenia in 75% vs 62% and leukopenia in 35% vs 27%). Other grade 3 or 4 adverse events included febrile neutropenia in 8% vs 6%, infections in 8% vs 4%, gastrointestinal events in 12% vs 0%, and peripheral neuropathy in 3% vs 2%. Serious adverse events occurred in 26% vs 13% of patients. Some patients developed second primary malignancies: one patient in the BV-AVD group (renal cell carcinoma) and two in the ABVD group (renal cell carcinoma and basal cell carcinoma).

The investigators concluded, “BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.”

Luc-Matthieu Fornecker, MD, PhD, of the Department of Hematology, Institut de Cancérologie Strasbourg Europe (ICANS), is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Takeda Pharmaceuticals. For full disclosures of the study authors, visit

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