S200: 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
Year: 2022
Type: article
Abstract: Background: In classical Hodgkin lymphoma (cHL), improved overall survival (OS) with first-line treatment using new combinations has seldom been observed compared with existing approaches. Five-year data from the randomized phase 3 ECHELON-1 study (NCT01712490) supported long-term progression-free survival (PFS) with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in patients (pts) with previously untreated stage III/IV cHL, regardless of interim positron emission tomography (PET) status. The long-term safety profile of A+AVD was manageable, and numerically fewer secondary malignancies were reported versus ABVD, as well as a greater number of pregnancies (Straus et al, Lancet Haematol 2021). Aims: To report the pre-specified OS analysis from ECHELON-1, as well as relevant long-term safety data, after approximately 6 years of follow-up (cut-off June 1, 2021). Methods: Pts were randomized 1:1 to receive up to 6 cycles of A+AVD (n=664) or ABVD (n=670) on day 1 and 15, every 28 days. PFS per investigator was reported for long-term follow-up. The key secondary end point was OS, which was an event-driven, pre-specified, alpha-controlled analysis in the intention-to-treat population, with a prespecified interim analysis after 103 deaths. Analysis of OS in prespecified subgroups was exploratory and was not adjusted for multiplicity. Informed consent was obtained for all pts. Results: In total, 39 OS events in the A+AVD arm and 64 in the ABVD arm had occurred at a median follow-up of 73 months, significantly favoring A+AVD (hazard ratio [HR] 0.590; 95% CI 0.396–0.879; p=0.009). There was a consistent OS benefit for A+AVD vs ABVD across prespecified subgroups, including: stage III (HR: 0.863; 95% CI 0.452–1.648) and stage IV disease (HR: 0.478; 95% CI 0.286–0.799) at diagnosis, pts who were PET-negative at cycle 2 (PET2)-negative (HR: 0.583; 95% CI 0.338–0.856) and PET2-positive (HR: 0.163; 95% CI 0.037–0.717), pts aged <60 years (HR: 0.509; 95% CI 0.291–0.890), pts aged ≥60 years (HR: 0.829; 95% CI 0.469–1.466), and across all geographies, including Europe (HR: 0.783; 95% CI 0.467–1.315) and North America (HR: 0.327; 95% CI 0.153–0.699). The 6-year PFS estimate was 82.3% (79.1–85.0) vs 74.5% (70.8–77.7) with A+AVD vs ABVD, respectively (HR: 0.678; 95% CI: 0.532–0.863). The long-term safety profile of A+AVD was comparable to that of ABVD. In both A+AVD and ABVD groups, treatment-emergent peripheral neuropathy continued to resolve or improve, with 86% (379/443) and 87% (249/286) of cases in the A+AVD and ABVD arms either completely resolving (72% vs 79%) or improving (14% vs 8%) by last follow-up. Overall, 23 secondary malignancies in the A+AVD arm and 32 in the ABVD arm were reported. Pregnancies and live births were reported by a greater number of female pts in the A+AVD group vs the ABVD group (49 vs 28 and 42 vs 19, respectively) and there were no stillbirths reported during the study. There were no new safety signals. Summary/Conclusion: There was a statistically significant 41% reduction in the risk of death with A+AVD vs ABVD, with a consistent OS benefit across prespecified subgroups. The long-term safety profile was manageable, consistent with prior reports. These data support A+AVD as a preferred option for previously untreated stage III and IV cHL.
Source: HemaSphere
Institutions: Copenhagen University Hospital, Rigshospitalet, Mayo Clinic, Memorial Sloan Kettering Cancer Center, Samsung Medical Center, Sungkyunkwan University, Centre Antoine Lacassagne, University of Tennessee at Knoxville, University of Rochester Medicine, University of Rochester, Stanford Medicine, Stanford University, Rutgers Cancer Institute, Medical University of Lodz, Washington University in St. Louis, National Cancer Center, Massachusetts General Hospital, Seagen (United States), Manchester Academic Health Science Centre, University of Manchester, The Christie NHS Foundation Trust
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W4283317434