As reported in The Lancet by Peter Borchmann, MD, and colleagues, the phase III HD21 trial showed that first-line positron-emission tomography (PET)-guided BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) exhibited greater efficacy and tolerability vs PET-guided eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced-stage classical Hodgkin lymphoma.

Peter Borchmann, MD

Study Details

In the open-label trial, 1,482 evaluable patients from sites in eight European countries and Australia were randomly assigned between July 2016 and August 2020 to receive BrECADD (n = 742; 21-day cycles of brentuximab vedotin at 1.8 mg/kg on day 0, etoposide at 150 mg/m² on days 1–3, cyclophosphamide at 1,250 mg/m² on day 1, doxorubicin at 40 mg/m² on day 1, dacarbazine at 250 mg/m² on days 2–3, and dexamethasone at 40 mg/m² on days 1–4) or eBEACOPP (n = 740; 21-day cycles of  etoposide at 200 mg/m² on days 1–3, doxorubicin at 35 mg/m² on day 1, cyclophosphamide at 1,250 mg/m² on day 1, bleomycin at 10 mg/m² on day 8, vincristine at 1.4 mg/m² on day 8,  procarbazine at 100 mg/m² on days 1–7, and prednisone at 40 mg/m² on days 1–14). Patients with negative findings on PET-2 received four cycles of therapy; those with positive findings on PET-2 received six cycles.

The primary outcome measures were treatment-related morbidity (defined as nonhematologic grade 3–4 toxicity and grade 4 hematologic toxicity) and progression-free survival.

Treatment-Related Morbidity

Treatment-related morbidity occurred in 42% of patients in the BrECADD group vs 59% of the eBEACOPP group (relative risk = 0.72, 95% confidence interval [CI] = 0.65–0.80, P < .0001). Hematologic grade 4 events occurred in 52% of the eBEACOPP group vs 31% of the BrECADD group (P < .0001).

Progression-Free Survival

Median follow-up was 48 months. BrECADD was associated with significantly improved progression-free survival vs eBEACOPP (hazard ratio = 0.66, 95% CI = 0.45–0.97, P = .035). Rates at 4 years were 94.3% (95% CI = 92.6%–96.1%) vs 90.9% (95% CI = 88.7%–93.1%).

A total of 64% of patients in each group had negative PET-2 and received four treatment cycles. Among patients with negative PET-2 findings, 4-year progression-free survival was 96.8% (95% CI = 95.0%–98.5%) vs 92.9% (95% CI = 90.4%–95.4%). Among patients with positive PET-2 findings, 4-year progression-free survival was 90.3% (95% CI = 86.6%–94.3%) vs 87.8% (95% CI = 83.4%–92.4%).

Among all patients, overall survival at 4 years was 98.6% (95% CI = 97.7%–99.5%) and 98.2% (95% CI = 97.2%–99.3%).

The investigators concluded, “BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma.”

Peter Borchmann, MD, of Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany, is the corresponding author for The Lancet article.

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