Brentuximab vedotin plus chemotherapy for patients with previously untreated, stage III or IV Lclassical Hodgkin lymphoma: 5-year update of the phase 3 ECHELON-1 STUDY (NCT01712490)

Abstract

In the ECHELON-1 study, brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) significantly improved modified progression-free survival (PFS) per independent review in patients (pts) with newly diagnosed Stage III/IV classical Hodgkin lymphoma (cHL) vsdoxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (Connors, NEJM 2018) and durable PFS per investigator (INV) benefits with A+AVD vs ABVD were seen with extended follow-up (Bartlett, Blood 2019; Straus, Blood 2020). We report updated efficacy and safety data after 5 years’ follow-up (cutoff date 18 Sep 2020). Pts with newly diagnosed Stage III/IV cHL were randomised 1:1 to up to 6 cycles of A+AVD (n=664) or ABVD (n=670) on days 1 and 15 of a 28-day cycle. Interim PET scan after cycle 2 (PET2) was mandated. Analyses were performed for PFS per INV, peripheral neuropathy (PN) resolution and improvement (improvement by ≥1 grade [G] from worst G by latest assessment) in pts with ongoing PN at end of treatment, rate of secondary malignancies, and pregnancy incidence and outcomes among pts and partners. After 60.9 months median follow-up (95% confidence interval [CI] 55.2–56.7), estimated 5-year PFS per INV was 82.2% (95% CI 79.0– 85.0) for A+AVD and 75.3% (95% CI 71.7–78.5) for ABVD, favouring A+AVD vs ABVD (hazard ratio [HR] 0.681; 95% CI 0.534–0.867; p=0.002). Estimated 5-year PFS with A+AVDvsABVD in the intention to treat population was 84.9% vs 78.9% in PET2– pts (HR 0.663; 95% CI 0.502–0.876; p=0.004) and 60.6%vs 45.9% in PET2+ pts (HR 0.702; 95% CI 0.393–1.255; p=0.229). In A+AVD and ABVD arms, 85% and 86% of pts with treatment-emergent PN had complete resolution or improvement of symptoms. In A+AVD and ABVD arms, PN was ongoing in 29% and 21% of pts, respectively, most of which were G1–2. In total, 131 pregnancies were reported; the proportion of ongoing pregnancies or live births in female pts was similar in both arms (A+AVD arm 85%, ABVD arm 74%). With 5 years’ follow-up, sustained PFS benefit was observed with A+AVD vs ABVD that was independent of disease stage and PET2 status. In addition, treatment adaptation by interim PET2 status is not required for A+AVD and bleomycin exposure is avoided. As most historical cHL relapses occur within the first 5 years (Radford, BMJ 1997), the durable and robust treatment benefit and manageable safety profile of A+AVD in ECHELON-1, suggest that A+AVD is an attractive treatment option for all pts with previously untreated Stage III/IV cHL.