Although advancements in the treatment of classical Hodgkin lymphoma have increased the 5-year relative survival rate of patients with the disease to nearly 90%, dose-intensified treatment strategies may increase the risk for acute and long-term toxicities.

The German Hodgkin Study Group (GHSG) HD21 trial compared the BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) chemotherapy regimen with the current standard-of-care BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) regimen in a positron-emission tomography (PET)-adapted approach in patients with advanced-stage classical Hodgkin lymphoma. The final analysis of the trial found BrECADD to be significantly more effective than a regimen of BEACOPP. The therapeutic combination was associated with an unprecedentedly high 4-year progression-free survival, reducing the risk of disease progression, relapse, or death by one-third. In combination with an abbreviated therapy duration of 3 months for the majority of patients and a favorable tolerability, treatment with PET-guided BrECADD sets a new benchmark for the treatment of late-stage classical Hodgkin lymphoma, concluded the study authors. The study was presented during the 2024 ASCO Annual Meeting by Peter Borchmann, MD, and colleagues (Abstract LBA7000).

Peter Borchmann, MD

Study Methodology

The intention-to-treat cohort for this analysis consisted of 1,482 adult patients with advanced-stage classical Hodgkin lymphoma. The median age of the cohort was 31.1 years and 44% were female. Patients were randomly assigned to receive an individualized four or six cycles of either BEACOPP or BrECADD guided by PET after two cycles (PET2). The co-primary endpoints included treatment-related morbidity and noninferiority in terms of progression-free survival. Testing for superiority was planned with mature follow-up of 4 years. An adjusted alpha level of 0.047 was required to cross the efficacy boundary for superiority.

Results

Patients were randomly assigned in a 1:1 ratio; 742 received BrECADD and 740 received BEACOPP. The researchers found that PET2 was negative in 424 (57.5%) and 426 (58.2%) patients receiving BrECADD and BEACOPP, respectively, after four treatment cycles.

With a median follow-up of 48 months, 4-year progression-free survival was 94.3% in those receiving BrECADD (95% confidence interval [CI] = 92.6%–96.1%) and 90.9% in those receiving BEACOPP (95% CI = 88.7%–93.1%; hazard ratio = 0.66, 95% CI 0.45–0.97, P = .035). The progression-free survival benefit of BrECADD was driven by a reduction in early treatment failures, such as primary progression within 3 months (5 vs 15) or early relapse between months 3 and 12 (11 vs 23), and was observed across all investigated subgroups.

PET2-negative patients in the BrECADD group showed a 4-year progression-free survival rate of 96.5%. Four-year overall survival was 98.5% for those in the BrECADD group and 98.2% for those in the BEACOPP group. Analyses of gonadal function demonstrated significantly higher follicle-stimulating hormone recovery rates after 1 year in both men (67% vs 24%) and women (89% vs 68%), with higher birthrates in the BrECADD group (n = 60 vs n = 43). 

Conclusion

“BrECADD is significantly more effective than BEACOPP and is associated with an unprecedentedly high 4-year progression-free survival, reducing the risk of progression, relapse, or death by a third. Together with an abbreviated treatment duration of only 3 months for the majority of patients and a favorable tolerability, treatment with PET2-individualized BrECADD sets a new benchmark for the treatment of adult patients with advanced-stage classical Hodgkin lymphoma,” concluded the study authors.

Disclosure: Funding for this study was provided by Takeda Oncology. For full disclosures of the study authors, visit coi.asco.org.