BrECADD Regimen Improves PFS vs eBEACOPP Regimen in Advanced Classical Hodgkin Lymphoma

The novel BrECADD regimen comprised of brentuximab vedotin (Adcetris), etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone elicited superior progression-free survival (PFS) outcomes vs eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced-stage classical Hodgkin lymphoma and had a promising benefit-risk profile, according to findings from the phase 3 GHSG HD21 study (NCT02661503).

Data presented at the 2024 ASCO Annual Meeting revealed that 42% of patients in the BrECADD arm experienced a treatment-related morbidity event (TRME) compared with 59% in the eBEACOPP arm (P < .0001). Additionally, reductions in red blood cell transfusions (24% vs 52%) and platelets (34% vs 17%), respectively, were observed.

At a median follow-up of 48 months, estimated 4-year PFS was superior in the BrECADD arm compared with the BEACOPP arm, at 94.3% (95% CI, 92.6%-96.1%) vs 90.9% (95% CI, 88.7%-93.1%), respectively (HR = 0.66; 95% CI, 0.45-0.97; P = .035). Four-year overall survival (OS) rates were 98.5% with BrECADD vs 98.3% with eBEACOPP.

“Intensified chemotherapy offers better lymphoma control than less intensive treatment, however, this comes at a cost of more short- and long-term treatment-related adverse effects. [Regarding] the risk-to-benefit ratio, [there is] efficacy on one hand and tolerability in the other,” study author, Peter Borchmann, MD, assistant medical director in the Department of Haematology and Oncology, head of the lymphoma programme and head of the Certified Centre for Haematological Malignancies at the University Hospital of Cologne in Germany, said in a presentation of the data. “[Tolerability] is highly relevant in a young patient cohort with a high cure rate and a long-life expectancy.”

Borchmann also noted that the 4-year PFS superiority observed with the BrECADD regimen was unprecedented in prior German Hodgkin Study Group trials.

GHSG HD21 is an international, randomized trial that was conducted in 233 treatment centers across 9 different countries. The trial included 1500 patients with classical Hodgkin lymphoma (age range, 18-60) who were randomly assigned 1:1 to receive either 2 cycles of BrECADD or 2 cycles of eBEACOPP before undergoing interim PET/CT staging to determine if they had a complete metabolic response. Patients who were PET2-negative received 2 more cycles of the prescribed regimen, while those who were PET2-positive received 4 more cycles.

Additional data revealed that FSH as marker for gonadal damage fully recovered more frequently after 4 years in the BrECADD arm than the eBEACOPP arm in women (95.7% vs 73.4%) and men (86.6% vs 39.8%), respectively.

The 48-month PFS rates for those with PET2-negative disease after 2 cycles were 93.0% (95% CI, 90.5%-95.5%) and 96.8% (95% CI, 95.1%-98.5%) in the BEACOPP and BrECADD groups, respectively. For those with PET2-positive disease, the 48-month PFS rates were 87.9% (95% CI, 83.5%-92.5%) and 90.4% (95% CI, 86.7%-94.3%), respectively.

Furthermore, secondary primary myelodysplastic syndrome or acute myeloid leukemia was rare and occurred in 2 patients treated with the BrECADD regimen. Severe sensory polyneuropathy was also rare, occurring in at grade 3 in 1% of patients; severe sensory polyneuropathy persisted after 1 year follow-up in 1 patient.

“To conclude the overall risk-benefit ratio of PET2-guided individualized BrECADD is very good,” Borchmann said. “We therefore recommend BrECADD as a standard treatment option for advanced-stage classical lymphoma patients.”

Reference

Borchmann P, Moccia AA, Greil R, et al. Tolerability and efficacy of BrECADD versus BEACOPP in advanced stage classical Hodgkin lymphoma: GHSG HD21, a randomized study. J Clin Oncol. 2024;42(suppl 17):LBA7000). doi:10.1200/JCO.2024.42.17_suppl.LBA7000