Abstract P029

Ten-year follow-up of ECHELON-1: overall survival and long-term safety with Brentuximab vedotin plus AVD versus ABVD in patients with previously untreated advanced classic Hodgkin lymphoma

Background: The phase 3 ECHELON-1 study (NCT01712490) compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients (pts) with previously untreated stage III/IV classic Hodgkin lymphoma (cHL). A 7-year follow-up (FU) analysis showed durable progression-free survival and overall survival (OS) benefits, and no new safety signals with A+AVD versus ABVD. We report 10-year FU data from ECHELON-1.

Methods: Pts were assigned 1:1 to receive up to 6 cycles of A+AVD (n=664) or ABVD (n=670) on days 1 and 15, every 28 days. OS was investigator-assessed in the intent-to-treat population (data cut-off [DCO] December 16, 2025). Long-term safety was evaluated in all pts who received ≥1 dose of any study medication (A+AVD, n=662; ABVD, n=659) and included subsequent anti-cancer therapies, secondary malignancies, peripheral neuropathy (PN) resolution/improvement, and pregnancies.

Results: At DCO, with a median FU of 120 months (95% CI 117.0–121.2), estimated 10-year OS rates were 90.3% (95% CI: 87.3–92.6) with A+AVD and 84.9% (95% CI: 81.4–87.8) with ABVD (hazard ratio 0.59 [95% CI 0.42–0.83]; P=0.002; Figure). A+AVD was associated with proportionally fewer deaths than ABVD (8% vs 13%). In the A+AVD and ABVD arms, 21% and 25% of pts had ≥1 subsequent anti-cancer therapy, respectively; chemotherapy was most common (13% A+AVD; 17% ABVD). Secondary malignancies were reported in 5% of pts (A+AVD) and 7% pts (ABVD), which included solid tumors (4% A+AVD; 4% ABVD) or hematological malignancies (2% A+AVD; 3% ABVD). Treatment-emergent PN was ongoing in 116/443 (26%) pts who originally reported PN in the A+AVD arm (15% grade 1; 8% grade 2; 3% grade 3; <1% grade 4) and in 56/286 (20%) pts in the ABVD arm (13% grade 1; 5% grade 2; 1% grade 3). PN resolved or improved in 86% of pts with A+AVD (74% resolved/12% improved) and 87% of pts with ABVD (80%/7%). Median (range) time to complete PN resolution and improvement was 36 (0–507) and 42 (8–392) weeks with A+AVD, and 17 (0–530) and 22 (2–213) weeks with ABVD, respectively. Pregnancies occurred in 94 pts (A+AVD, n=60; ABVD, n=34) and 87 partners of male pts (n=42; n=45). Live births were reported in 77 pts (A+AVD, n=51; ABVD, n=26) and 77 partners of male pts (n=37; n=40), with no stillbirths reported.

Conclusion: In this 10-year FU, A+AVD demonstrated a sustained OS benefit vs ABVD in advanced cHL, with manageable long-term safety.