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Significantly improved outcomes with combination of brentuximab vedotin and AVD compared to standard ABVD as frontline therapy for previously untreated advanced Hodgkin lymphoma

Results of the phase III ECHELON-1 study demonstrated that the combination of the CD30 antibody-drug conjugate brentuximab vedotin (BV) with AVD chemotherapy (adriamycin, vinblastine, dacarbazine) as frontline therapy for patients with advanced Hodgkin lymphoma (HL) was associated with a significant 23% reduction in the risk of disease progression or death compared to ABVD (AVD plus bleomycin). As such, this study results represent the first successful effort in more than 30 years to improve outcomes of first-line treatment in patients with advanced HL without escalating the toxicity of the chemotherapy to unacceptable levels.1

Currently, ABVD is the preferred first-line treatment for patients with advanced HL in the US. Also in Europe this regimen is often used, although (escalated) BEACOPP is also often used. With these chemotherapy regimens, 70% to 75% of patients can be cured. However, 25% to 30% of advanced-stage HL patients have refractory disease or relapse following these frontline strategies. BV is a CD30-directed antibody-drug conjugate approved for classical HL after failure of autologous stem cell transplantation (ASCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates and as post auto-HSCT consolidation for patients at high risk of relapse or progression.

In a previously reported phase I study, combining BV with AVD led to a complete response rate of 96%, with 5-year failure free survival (FFS) and overall survival (OS) rates of 92% and 100%, respectively.2 These data formed the basis for the large, phase III ECHELON-1 study.

ECHELON-1 is an unblinded, open-label, randomized, multicentre, phase 3 study comparing BV plus AVD with ABVD as frontline therapy in previously untreated advanced HL. In total, 1334 adult patients with stage III/IV classical HL, with an ECOG performance status of 0-2, measurable disease  and an adequate liver and renal function were randomised (1:1) to receive BV plus AVD (brentuximab vedotin 1.2 mg/kg, doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) or ABVD (adriamycin 25mg/m2, bleomycin 10 units/m2, vinblastine 6 mg/m2 and dacarbazine 375 mg/m2) IV on days 1 and 15 of up to six 28-day cycles.  Per protocol, patients with a PET scan Deauville score of 5 after cycle 2 were allowed to switch to the alternative therapy at the treating physician’s discretion. The primary endpoint of the study was modified PFS (defined as time to progression, death, or evidence of incomplete response followed by subsequent anticancer therapy) determined by independent review facility (IRF) assessment.2

The median age of patients in the trial was 36 years, 58% was male and two thirds of patients had Ann Arbor stage IV disease. About 60% of patients had B symptoms and 22% had bone marrow involvement. Half of the patients had 2 to 3 IPS risk factors and 25% had an IPS score of 4 to 7. ECHELON-1 revealed that patients who were treated with BV plus AVD had a 23% lower risk of disease progression or death than patients randomised to ABVD (HR[95%CI]: 0.77[0.60-0.98]; p= 0.0348). The 2-year modified PFS estimates were 82.1% with BV + AVD and 77.2% with ABVD. There were 28 deaths in the BV + AVD arm and 39 in the ABVD arm (interim overall survival HR 0.721 [95% CI 0.443–1.173]; p=0.186).2 Furthermore, investigators reported that 33% fewer BV + AVD patients received subsequent chemotherapy and that 33% fewer BV + AVD patients received subsequent high-dose chemotherapy + transplant compared to ABVD.2

Neutropenia was reported in 58% of patients receiving BV + AVD and in 45% of patients on ABVD (febrile neutropenia in 19% and 8%, respectively). Grade ≥3 infections were more common in the BV + AVD arm than in the ABVD arm (18% vs. 10%). In patients receiving BV + AVD, primary prophylaxis with G-CSF (N=83) reduced febrile neutropenia from 19% to 11% and reduced the incidence of grade ≥3 infections and infestations from 18% to 11%. Peripheral neuropathy (PN) occurred in 67% of patients receiving BV + AVD and in 43% of patients treated with ABVD (grade ≥3: 11% vs. 2%, respectively).

Importantly, 67% of the patients who experienced PN in the BV + AVD arm had resolution or improvement of PN by at least 1 grade at their last follow-up. Due to the bleomycin in the regimen, pulmonary toxicity was more frequent and more severe with ABVD compared to BV + AVD. In fact, with ABVD 3% of patients experienced grade ≥3 interstitial lung disease, while this incidence was lower than 1% with BV + AVD.2

Compared with standard ABVD, the combination of BV and AVD was associated with a significant delay in the disease progression of patients with advanced classical HL. This establishes BV+AVD as a new frontline option for patients with advanced-stage HL.


1. Connors J, Jurczak W, Straus D, et al. Brentuximab Vedotin Plus Doxorubicin, Vinblastine, Dacarbazine (A+AVD) As Frontline Therapy Demonstrates Superior Modified Progression-Free Survival Versus ABVD in Patients with Previously Untreated Stage III or IV Hodgkin Lymphoma (HL): The Phase 3 Echelon-1 Study. Presented at ASH 2017; Abstract 6.
2. Connors J, Ansell S, Fanale M, et al. Five-year follow-up of brentuximab vedotin combined with ABVD or AVD for advanced-stage classical Hodgkin lymphoma. Blood 2017;130(11):1375-7.

Speaker Joseph Connors


Joseph M.Connors, MD,P PhD, Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada


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