Brentuximab vedotin with chemotherapy for Stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study

Abstract

The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with AVD (A+AVD) exhibited superior modified PFS versus ABVD for the frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL) (NCT01712490; 2011-005450-60). Maturing data from positron emission tomography (PET)-adapted trials highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET2(-) patients. We present here an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. 1334 patients with stage III or IV cHL were randomized 1:1 to receive six cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET scan after cycle 2 (PET2) was required. At a median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2(-) patients aged <60 years were 87.2% versus 81.0%, respectively. A beneficial trend in PET2(+) patients aged <60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% versus 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy (PN) on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL which is consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or exposure to bleomycin.