Abstract P009

Brentuximab vedotin plus chemotherapy in patients with previously untreated Stage III/IV classical Hodgkin lymphoma: seven-year overall survival analysis from ECHELON-1

Background: After 6-years’ follow-up in the ECHELON-1 study (NCT01712490), patients with Stage III/IV classical Hodgkin lymphoma (cHL) treated with A+AVD (brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine) showed significant improvements in overall survival (OS) and progression-free survival (PFS) versus patients treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), with a comparable safety profile. We present OS and PFS data after a median follow-up of 7 years.

Methods: OS and PFS per investigator assessment were evaluated in the intent-to-treat (ITT) population (data cut-off March 11, 2023). Patients were randomized 1:1 to receive ≤6 cycles of A+AVD (n=664) or ABVD (n=670) on days 1 and 15, every 28 days. Positron emission tomography scan after cycle 2 (PET2) evaluation was mandatory. Long-term safety outcomes included resolution or improvement of peripheral neuropathy (PN), incidences and outcomes of pregnancies among female patients and their partners, and rates of second malignancies.

Results: At a median follow-up of 89.3 months, 7-year OS rates significantly favored A+AVD versus ABVD (93.5% [95% CI 91.1–95.2] vs 88.8% [95% CI 85.8–91.1]; HR 0.62 [95% CI 0.42–0.90], P = 0.011). Consistent benefit with A+AVD over ABVD in most subgroups analyzed, including age <40 years and Stage IV disease, was observed (Table). Seven-year PFS rates with A+AVD versus ABVD were 82.3% (95% CI: 79.1–85.0) vs 74.5% (95% CI: 70.8–77.7), respectively (HR, 0.68; 95% CI: 0.53–0.86; P = 0.001). At the last follow-up, PN improved or resolved in most patients (A+AVD: 86.0%; ABVD: 87.1%). Median (range) time to complete resolution of PN was 16 (0–373) vs 10 (0–343) weeks with A+AVD versus ABVD; corresponding median (range) time to improvement was 42 (2–182) vs 19 (15–142) weeks. PN was ongoing in 27.5% (122/443; 11.7% grade ≥2) and 20.3% (58/286; 7.0% grade ≥2) of A+AVD- and ABVD-treated patients, respectively. Furthermore, 84/92 patients and their partners reported livebirths/pregnancies with A+AVD and 59/73 with ABVD; no stillbirths were recorded. Second malignancies were reported in 5.0% of A+AVD- and 5.9% of ABVD-treated patients.

Conclusions: At a median follow-up of 7 years, patients with Stage III/IV cHL treated with A+AVD demonstrated sustained improvements in PFS and OS, compared with those treated with ABVD, with PFS rates suggesting curability. Additionally, the safety profile of A+AVD remained unchanged with no new safety signals.