BrECADD Recommended as Standard Treatment for Advanced-Stage, Classical Hodgkin Lymphoma After Promising PFS Results

BrECADD guided by positron emission tomography (PET) after 2 cycles showed better tolerability and efficacy than eBEACOPP for the first-line treatment of adult patients with newly diagnosed, advanced-stage, classical Hodgkin lymphoma, according to a study published in The Lancet.

The randomized, multicenter, parallel, open-label, phase 3 trial was led by Peter Borchmann, MD, of the University Hospital of Cologne. Of 1,500 patients (median age, 31 years) included in the study, 749 received BrECADD guided by PET after 2 cycles, and 751 received eBEACOPP [escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone]. Patients received cycles of BEACOPP and BrECADD in 21-day intervals, and treatment was administered at the highest dose level.

The primary end points were tolerability, as defined by treatment-related morbidity, and efficacy as assessed by progression-free survival (PFS). Secondary end points included adverse events, frequency of complete response, overall survival, gonadal toxicity and function, secondary primary malignancies, event-free survival, and patient-reported outcomes.

Although most patients in both treatment groups had at least 1 adverse event, patients in the BrECADD group had a lower incidence of at least 1 treatment-related morbidity event (42% vs 59%, respectively; 95% CI, 0.65-0.80; P<0.0001). The incidence of grade 3 or higher infections was similar between the 2 groups (19% vs 20%), and the incidence of grade 3 or higher neutropenic fever was lower with eBEACOPP than with BrECADD (21% vs 28%, respectively).

There were also more dose reductions in the eBEACOPP group than in the BrECADD group. For patients receiving BrECADD, the most common reasons for dose reductions included leukopenia in 34% and thrombocytopenia in 23%.

At a median follow-up of 48 months, BrECADD improved PFS with a hazard ratio (HR) of 0.66 (0.45-0.97; P=0.035). Estimates of 4-year PFS were 94.3% (95% CI, 92.6%-96.1%) for BrECADD and 90.9% (95% CI, 8.87%-93.1%) for eBEACOPP . The 4-year overall survival rates were comparable between the BrECADD and eBEACOPP groups (98.6% vs 98.2%, respectively).

Dr. Borchmann and colleagues wrote that “after finding non-inferiority of BrECADD at an interim analysis, the superiority test revealed a significant progression-free survival benefit of BrECADD versus eBEACOPP…The increase in efficacy was driven by a reduction in refractory cases and early relapses, thereby reflecting the importance of early definitive disease control in classical Hodgkin lymphoma to achieve favourable, long-term outcomes.”

As for secondary end points, 2% of patients in the eBEACOPP group and 3% of patients in the BrECADD group had second primary malignancies. The rates of gonadal function recovery were higher in both male (86.0%) and female (95.3%) patients in the BrECADD group compared with male (39.2%) and female (72.5%) patients in the eBEACOPP group.

Study limitations include the exclusion of patients older than 60 from the study as eBEACOPP is only recommended for patients aged 18 to 60 years.

“With the individualised PET-2-guided, shortened treatment, the BrECADD regimen shows a favourable risk–benefit profile for most patients,” Dr. Borchmann and colleagues concluded. “Therefore, we recommend BrECADD as a standard treatment option for adult patients with newly diagnosed, advanced-stage, classical Hodgkin lymphoma.”

This research was funded by Takeda Oncology.

Reference

Borchmann P, Ferdinandus J, Schneider G, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial. Lancet. 2024;404(10450):341-352. doi:10.1016/S0140-6736(24)01315-1