BrECADD Outperforms Standard Chemo in Tolerability and PFS in Classical Hodgkin Lymphoma
A new brentuximab vedotin-containing regimen for classical Hodgkin lymphoma has been shown to be more tolerable and effective than the current standard.
Peter Borchmann, MD
A treatment regimen known as BrECADD, which involves brentuximab vedotin (Adcetris), shows promise compared with the intense chemotherapy regimen, eBEACOPP, in regard to tolerability and progression-free survival (PFS) results among adult patients with stage IIB, III, or IV classical Hodgkin lymphoma. Findings come from the GHSG HD21 study and were presented ahead of the 2024 ASCO Annual Meeting.1
The BrECADD regimen consisted of brentuximab vedotin (Adcetris), etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. The eBEACOPP had bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.
“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 events. So [regarding] the risk-to-benefit ratio, [there is] efficacy in one hand and tolerability in the other,” study author, Peter Borchmann, MD, of the University Hospital Cologne, Center for Integrated Oncology, 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.”
Of note, Borchmann mentioned that the average age of diagnosis for classical Hodgkin lymphoma is approximately 30 years old.
GHSG HD21 is an international, randomized phase III trial that was conducted in 233 treatment centers across nine different countries. The trial included 1500 patients with classical Hodgkin (age range, 18-60) lymphoma who were randomized 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.
Findings showed that there was a lower rate of treatment-related morbidity (TRMB; defined as acute and severe toxicities related to treatment) in the BrECADD arm, at 42%, compared to the eBEACOPP arm, at 59% (P < 0.0001). This included:
- Reduction in red blood cell transfusions (24% vs 52% for the BreCADD and eBEACOPP arms, respectively).
- Reduction in the platelet transfusions (17% vs 34%, respectively).
- Only 1% of patients experiencing grade 3 severe sensory polyneuropathy, and no patients experiencing the adverse event at grade 4. Severe sensory polyneuropathy persisted after 1 year follow-up in only 1 patient.
- Gonadal damage, as marked by FSH, fully recovered more frequently after 4 years in the BrECADD group than the eBEACOPP group in women (95.7% vs 73.4%, respectively) and men (86.6% vs 39.8%, respectively).
- Two out of 738 patients in the BrECADD group developed second primary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
At a median follow-up of 48 months, estimated 4-year PFS was also superior in the BrECADD arm compared to the BEACOPP arm, at 94.3% (95% CI, 92.6%-96.1%) and 90.9% (95% CI, 88.7%-93.1%), respectively (HR = 0.66; 95% CI, 0.45-0.97; P = .035).
The 48-month PFS rates for those who were PET2-negative 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 who were PET2-positive, the 48-month PFS rates were 87.9% (95% CI, 83.5%-92.5%) and 90.4% (95% CI, 86.7%-94.3%).
Four-year overall survival (OS) was comparable between the two arms, at 98.5% with BrECADD and 98.3% with eBEACOPP.
The 4-year superiority observed with the BrECADD regimen was “unprecedented,” according to Borchmann.
“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.”
