BrECADD Regimen Reaches “Unprecedently High” PFS for Patients With Hodgkin Lymphoma

When PET is used to guide treatment of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) after 2 cycles, the regimen is significantly more effective than bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) in patients with advanced stage Hodgkin lymphoma, according to results presented by Peter Borchmann, MD, of University Hospital of Cologne, the Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, and the German Hodgkin Study Group, during a presentation at the 2024 American Society of Clinical Oncology Annual Meeting.¹

Peter Borchmann, MD, of University Hospital of Cologne

Image credit: European Society of Medical Oncology

The findings, according to Borchmann, challenge the standard of care of escalated BEACOPP (eBEACOPP) for these patients. eBEACOPP was introduced approximately 2 decades ago and it improved progression-free survival (PFS) and overall survival (OS) through the reduction of primarily progressive disease or early relapse,² the so-called “hit it hard and early” principle, he explained. Patients who were at higher risk of treatment failure benefited the most from this approach, but the risk for acute and persisting toxicities increased for all patients.

“That’s why the overall risk-to-benefit ratio of this approach was questioned,” Borchmann said. However, because of the high efficacy of eBEACOPP, PET was able to guide treatment and reduce intensity from 8 to only 4 cycles for most patients.³ The goal of the HD21 study (NCT02661503) was to improve on the treatment strategy by modifying the eBEACOPP regimen with brentuximab vedotin, which has a better risk-to-benefit profile than conventional chemotherapy, he noted.

BrECADD maintains the backbone of doxorubicin, cyclophosphamide, and etoposide, but brentuximab vedotin replaced bleomycin and vincristine, dacarbazine replaced procarbazine, and 4 days of dexamethasone replaced 14 days of prednisone.

In the final analysis of the international, randomized, phase 3 HD21 trial of nearly 1500 patients and a median follow-up of 48 months, BrECADD achieved an “unprecedentedly high” 4-year PFS rate of 94.3%, he said. Most (64%) patients only received 4 cycles of treatment, which equals a treatment duration of 12 weeks. The trial had a coprimary end point of reducing toxicity and improving PFS.

A total of 742 patients received BrECADD and 740 BEACOPP. In the trial, the median age was 31.1 years (range, 18-60) and 44% were female. For 57.5% of patients receiving BrECADD and 58.2% of patients on BECAOPP, PET after 2 cycles (PET2) was negative and they were scheduled to receive 4 treatment cycles.

At the interim analysis, 1 year ago, BrECADD was shown to be noninferior to BEACOPP, and at the final analysis being presented in 2024, BrECADD was found to be superior, Borchmann said. The overall 4-year PFS was 94.3% for BrECADD (95% CI, 92.6%-96.1%) compared with 90.9% for BEACOPP (95% CI, 88.7%-93.1%). Among patients who were PET2 negative, the 4-year PFS was 96.5% for BrECADD. The 4-year OS for these patients was 98.5% for BrECADD and 98.2% for BEACOPP.

Borchmann explained that BrECADD was better tolerated than escalated BEACOPP. The risk for acute and severe toxicities was reduced to 0.72 and more than 99% of patients had a resolution of these treatment-related morbidities at the 12-month follow-up. The recovery rate at 1 year is important for the population being treated, he noted.

“These patients are very young, and they face a life-threatening diagnosis,” Borchmann said. “So, they would accept treatment-emerging adverse events as long as they are primarily cured and as long as these adverse events would then disappear over time.”

The reduction of severe and acute toxicities was observed for all subgroups. Patients on BrECADD also had a clinically highly relevant reduction of neuropathy and gonadal dysfunction, he said.

“Due to this very favorable risk-benefit profile, we recommend individualized PET2-guided BrECADD as the standard treatment option for advanced stage classic Hodgkin lymphoma in this patient cohort,” Borchmann concluded.

This study was funded by Takeda.

References

1. 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. Presented at: ASCO 2024; May 31-June 4, 2024; Chicago, Illinois. Abstract LBA7000.

2. Diehl V, Franklin J, Pfreundschuh M, et al; and the German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003;348(24):2386-2395. doi:10.1056/NEJMoa022473

3. Borchmann P, Goergen H, Kobe C, et al. PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet. 2017;390(10114):2790-2802. doi:10.1016/S0140-6736(17)32134-7