An updated analysis of the ECHELON-1 trial supports the use of first-line brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) over doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for patients with stage III/IV classical Hodgkin lymphoma (cHL). These data were presented at the 2022 ASCO Annual Meeting by lead investigator Stephen M. Ansell, MD, PhD, Mayo Clinic, Rochester, MN.

“In ECHELON-1, 5-year follow-up analyses supported the long-term progression-free survival (PFS) benefit with first-line A+AVD versus ABVD in patients with stage III/IV cHL, independent of interim positron emission tomography status,” wrote Dr Ansell et al, who now present a prespecified overall survival (OS) analysis after approximately 6 years of follow-up.

A total of 1334 patients were randomized in a 1:1 ratio to receive up to 6 cycles of A+AVD (n = 664) or ABVD (n = 670) on day 1 and 15 of every 28-day cycle. The key secondary end point was OS.

At the point of median follow-up (73 months), 39 and 64 OS events had been reported in the A+AVD and ABVD arms, respectively, with OS significantly favoring A+AVD vs ABVD (hazard ratio [HR], 0.590; 95% confidence interval [CI], 0.396 to 0.879; P = .009).

According to the investigators, the estimated 6-year OS rates were 93.9% (95% CI, 91.6 to 95.5) and 89.4% (95% CI, 86.6 to 91.7) with A+AVD and ABVD, respectively, and there was a consistent OS benefit observed for A+AVD vs ABVD across prespecified subgroups.

For patients in the A+AVD versus ABVD arms, the 6-year PFS estimates were 82.3% (95% CI, 79.1 to 85.0) and 74.5% (95% CI, 70.8 to 77.7), respectively (HR, 0.678; 95% CI, 0.532 to 0.863).

Long-term safety profiles were comparable between the 2 treatment arms, and cases of treatment-emergent peripheral neuropathy continued to resolve or improve in both arms, with 86% (379/443) and 87% (249/286) of cases in the A+AVD and ABVD arms completely resolving (72% vs 79%) or improving (14% vs 8%) as of the last follow-up.

In the A+AVD versus ABVD arms, rates of second malignancies were lower (23 vs 32, respectively), while rates of pregnancies (49 vs 28) and live births (42 vs 19) were higher. The researchers reported no stillbirths, and no new safety signals were observed.

“A+AVD treatment resulted in a statistically significant 41% reduction in the risk of death vs ABVD, with a manageable safety profile consistent with prior reports. These outcomes confirm A+AVD as a preferred option for patients with previously untreated stage III/IV cHL,” concluded Dr Ansell and colleagues.

Source:

Ansell SM, Connors JM, Radford JA, 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. Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 7503.