New Treatment Paradigm Supersedes ABVD in Advanced Hodgkin Lymphoma: The ECHELON-1 Study

Phase 3 results from the ECHELON-1 study, presented at the 59th Annual Meeting & Exposition of the American Society of Hematology, showed superior modified progression-free survival (mPFS) after adding the modified anti-CD30 antibody brentuximab vedotin to doxorubicin, vinblastine, and dacarbazine (AVD) in patients with advanced Hodgkin lymphoma (HL) 

This presents a significant change in the standard frontline regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), which has not been modified for over 40 years, since it was first described, according to presenting author Joseph M. Connors, MD, medical oncologist, BC Cancer Agency, University of British Columbia, Canada.

About 30% of patients with advanced stage HL have relapsed or refractory disease following frontline ABVD. Add to that the pulmonary toxicity associated with bleomycin, which may then be dropped off from later cycles of chemotherapy.

Connors then shared the phase 2 results of ECHELON-1, which documented a 3-year PFS of 58% and a 3-year overall survival (OS) of 73%.1 “Of the 34 patients who had a complete response, 47% were progression free at 53 months,” he added. “Several studies have demonstrated that intensifying the ABVD regimen in these advanced-stage patients does not provide any survival advantage,” Connors said. Therefore, the considerations for their study design for the new regimen included:

• OS advantage

• Duration of follow-up

• Impact on fertility and short- and long-term organ damage

• Economics, especially in the context of supportive care such as the need for growth factors 

Patients enrolled in the open-label, global (218 study sites in 21 countries) ECHELON-1 study were randomized 1:1 to receive A+AVD (brentuximab vedotin 1.2 mg/kg, doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2) (n = 664) or ABVD (doxorubicin 25 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2) (n = 670) on days 1 and 15 of up to six 28-day cycles. “Patients with a [positron emission tomography] (PET) scan Deauville score of 5 after cycle 2 could switch to alternative therapy at the treating physician’s discretion,” Connors said.