Adult patients with previously untreated stage III/IV classical Hodgkin lymphoma (cHL) had improved overall survival (OS) rates when treated with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) compared with patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), according to six-year data from the ECHELON-1 trial. Results from the updated analysis of the phase III trial were presented at both the American Society of Clinical Oncology (ASCO) Annual Meeting1 and the European Hematology Association (EHA) 2022 Congress.2
“Brentuximab vedotin plus AVD should be considered by hematologists/oncologists as a standard for treating advanced-stage HL,” said first author Stephen Ansell, MD, PhD, of Mayo Clinic in Rochester, Minnesota.
In patients with cHL, data on an OS benefit from upfront treatment combinations over existing approaches are limited. Five-year follow-up data from ECHELON-1 supported the long-term progression-free survival (PFS) benefit with A+AVD versus ABVD in these patients.
In the updated analysis, Dr. Ansell and colleagues reported a prespecified OS analysis after approximately six years of follow-up. Patients were randomly assigned to receive six cycles of A+AVD (n=664) or ABVD (n=670) on days one and 15 as well as every 28 days. OS was the key secondary endpoint.
A+AVD resulted in a statistically significant improvement in OS versus ABVD (hazard ratio [HR] = 0.59; 95% CI 0.396-0.879; p=0.009), corresponding to a 41% reduction in the risk of death. At a median follow-up of 73 months, OS events occurred in 39 of the patients receiving A+AVD and 64 of the patients receiving ABVD. The estimated OS rates were 93.9% in patients receiving A+AVD (95% CI 91.6-95.5) and 89.4% in patients receiving ABVD (95% CI 86.6-91.7). The six-year estimated PFS rates were 82.3% in patients receiving A+AVD (79.1-85.0) versus 74.5% in patients receiving ABVD (70.8-77.7).
Overall, the long-term safety profile was comparable for both treatments, with no new safety signals identified. Treatment-emergent peripheral neuropathy continued to resolve or improve in both treatment groups with 86% and 87% of cases in the A+AVD and ABVD groups, respectively, either completely resolving (72% vs. 79%) or improving (14% vs. 8%) by last follow-up. For A+AVD compared with ABVD, there were fewer secondary malignancies (23 vs. 32) and more female patients reporting pregnancy (49 vs. 28) or live births (42 vs. 19). No stillbirths were reported.
“This study is one of the only trials to show a survival advantage for a new frontline treatment combination over the standard therapy,” Dr. Ansell said. “The study found that brentuximab vedotin added to AVD chemotherapy improved the PFS and OS of patients with advanced-stage HL compared to standard ABVD chemotherapy.”
Any conflicts of interest by the authors were made public at the time of presentation.
References
- Ansell S, Connors J, Radford J, et al. First-Line brentuximab vedotin plus chemotherapy to improve overall survival in patients with stage III/IV classical Hodgkin lymphoma: An updated analysis of Echelon-1. Abstract 7503. Presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, June 3, 2022; Chicago, Illinois.
- Hutchings M, Ansell S, Straus D, et al. Improved overall survival with first-line brentuximab vedotin plus chemotherapy in patients with stage III/IV classical Hodgkin lymphoma: 6-year analysis of Echelon-1. Abstract Presented at the European Hematology Association (EHA) 2022 Congress, June 10, 2022; Vienna, Austria.
