Brentuximab Vedotin-Based Regimen Shows Non-Inferior Efficacy to Standard of Care in cHL

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Treatment with brentuximab vedotin (Adcetris) plus the chemotherapy combination of etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) was found to be non-inferior to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPO) in patients with first-line classical Hodgkin lymphoma (cHL), according to findings from a phase 3 study (HD21; NCT02661503).¹

The findings were from the intent-to-treat population of 1,482 patients evaluated during the interim analysis, which was presented during the 17th International Conference on Malignant Lymphoma on June 17, 2023. The median follow-up in the study was 40 months. Importantly, the BrECADD regimen showed a 3-year progression-free survival (PFS) rate of 94.9% (99% CI, 92.8%-97.1%) compared with 92.3% (99% CI, 89.7%-94.9%) with the eBEACOPO regimen. The 1-year PFS was 97.5% (99% CI, 96%-99%) in the BrECADD arm, and the 3-year overall survival was 98.5% in both arms, according to a press release.¹

“Our mission in Hodgkin lymphoma is to cure patients with a first-line treatment that reduces the risk of cancer returning as much as possible so patients can go on with their lives,” said professor Peter Borchmann, MD, assistant medical director, Department of Hematology and Oncology at the University Hospital of Cologne, Germany and head of the Lymphoma Program, head of the German Hodgkin Study Group and trial chairman of the HD21 study, in the press release. “The mature results of this study demonstrate 3-year efficacy never previously observed in a phase 3 trial in advanced cHL and suggest that the BrECADD regimen may be the most effective therapy regimen currently available in advanced cHL.”

The safety of each regimen in patients who were 12-month post-treatment was in line with prior data from the study presented at the American Society of Hematology 2022 Annual Meeting.^1,2 The rate of grade ≥2 peripheral neuropathy was 1.9% with the BrECADD regimen vs 2.7% with the eBEACOPO regimen. Overall, most patients had no peripheral neuropathy or low-grade peripheral neuropathy events, including 98.1% of the BrECADD arm vs 97.3% of the eBEACOPO group.

Investigators utilized follicle-stimulating hormone (FSH) to evaluate preservation of fertility, and this information was obtained for 597 patients. Patients treated with the BrECADD had a numerically more favorable preservation of fertility compared with those who received the eBEACOPO regimen. The mean FSH levels were 29.4 among the eBEACOPO -treated at cycle 4 vs 31.8 at cycle 6, and FSH levels were 18.3 in the BrECADD-treated population at cycle 4, and 20.5 at cycle 6. Because continued FSH elevation correlates with impaired gonadal function, further analysis is warranted to decipher the relevance of the results, according to Seagan, Inc.

“We are enthusiastic about these strong and durable efficacy outcomes and tolerability findings of a [brentuximab vedotin] based chemotherapy regimen compared with an international standard chemotherapy. We are evaluating these results to determine next steps,” said Roger Dansey, president of research and development and chief medical officer at Seagen, Inc, in the press release.

The HD21 study is ongoing and recruiting patients with histologically confirmed classical Hodgkin lymphoma at first diagnosis with no prior therapy. To be eligible, patients must be between the ages of 18 and 60 years old with a stage IIB large mediastinal mass, extranodal lesions, or stage III/IV disease. Patients with composite lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma will be excluded, as will patients with a prior malignancy, and those previously treated with chemotherapy or radiotherapy.³

_REFERENCES:

_{1. Phase 3 trial of ADCETRIS® (brentuximab vedotin) with modified chemo regimen shows non-inferiority with unprecedented 3-year progression free survival of 94.9% vs less tolerable international standard of care in advanced classical Hodgkin lymphoma. News release. Seagen, Inc. June 20, 2023. Accessed June 21, 2023. https://tinyurl.com/4afer2y4}

_{2. Borchmann P, Moccia A, Grell R, et al. Treatment related morbidity in patients with classical hodgkin lymphoma: results of the ongoing, randomized phase III HD21 trial by the German Hodgkin Study Group. Blood. 2022;140(suppl 1):771-773. doi:10.1182/blood-2022-165917}

_{3. HD21 for advanced stages. ClinicalTrials.gov. Updated August 8, 2022. Accessed June 21, 2023. https://clinicaltrials.gov/ct2/show/NCT02661503?term=HD21&draw=2&rank=1}