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Classic Hodgkin lymphoma (cHL) patients with high-risk features have greater benefit from brentuximab vedotin + AVD versus ABVD compared with the overall study population

Previous results of the phase III ECHELON-1 trial demonstrated superiority of brentuximab vedotin + AVD over standard ABVD as first-line treatment of patients with classic Hodgkin lymphoma. During EHA 2018, results of a subanalysis of this trial indicate that patients with high-risk features (i.e. stage IV disease, or ≥1 extranodal disease sites) had a marked improvement in modified progression-free survival (mPFS) wit the brentuximab vedotin + AVD combination, compared to ABVD. In fact, the mPFS benefit seen in these high-risk patients was even better than the mPFS benefit observed in the ITT population.

In the open-label, global, randomized, phase III ECHELON-1 trial 1,334 patients were randomized (1:1) to receive up to 6 28-day cycles of brentuximab vedotin + AVD (brentuximab vedotin 1.2 mg/kg, doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2) or ABVD (AVD regimen + bleomycin 10 units/m2) intravenously on days 1 and 15 of each cycle. Previously, it was demonstrated that patients with stage III and IV cHL treated with frontline brentuximab vedotin + AVD compared to ABVD had a significant improvement of mPFS. At 2 years, the mPFS rates were 82.1% (95% CI: 78.8-85.0) versus 77.2% (95% CI: 73.7-80.4), respectively (HR:0.77; 95% CI: 0.60-0.98; p=0.0351).

At EHA 2018, Hutchings et al. presented data of the ECHELON-1 trial in specific, pre-specified high-risk subgroups. This subanalysis assessed the efficacy and safety of brentuximab vedotin + AVD versus ABVD in patients with cHL and high-risk features, including ≥1 extranodal sites of involvement, or stage IV disease. The subgroup analyses were performed on the primary endpoint of mPFS, which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

In total, 664 and 670 patients were randomized to brentuximab vedotin + AVD and ABVD, respectively. High-risk features at baseline were well balanced between the treatment groups with 64% and 63% of the patients having stage IV disease in the brentuximab vedotin + AVD and ABVD arms, respectively. In addition, 62% of the patients in each arm had ≥1 extranodal sites at baseline. Most pre-specified subgroups demonstrated a consistent trend towards a mPFS benefit with brentuximab vedotin + AVD compared to ABVD. Among patients with stage IV disease the 2-year mPFS was 82.0% with the brentuximab combination vs. 75.3% with ABVD (HR:0.711; 95% CI: 0.53-0.96; p=0.023). In the cohort of patients with ≥1 extranodal sites the 2-year mPFS rates were 82.4% and 74.9% with brentuximab vedotin + AVD and ABVD, respectively (HR:0.699; 95% CI: 0.52-0.94; p=0.02). In addition, patients with high-risk features treated with brentuximab vedotin + AVD, trended to an overall survival benefit: stage IV disease (2-year OS 97.4% versus 93.4% [HR:0.507, 95% CI: 0.27-0.97; p=0.037]), ≥1 extranodal sites (2-year OS 97.5% versus 93.4% [HR:0.431, 95% CI: 0.22–0.85; p=0.01]). The safety profile of brentuximab vedotin + AVD was comparable across all high-risk patient subgroups.

In conclusion, compared to standard ABVD, brentuximab vedotin + AVD in frontline trends favorably for mPFS and OS outcomes for patients with high-risk cHL defined as stage IV disease, or ≥1 extranodal disease sites. This mPFS benefit for high-risk patients is more than the benefit in the ITT population. As such, these results suggest that patients with high-risk cHL might have a greater treatment benefit with brentuximab vedotin + AVD compared with ABVD.


Hutchings M, Radford J, Gallamini A, et al. Brentuximab vedotin plus chemotherapy in high risk advanced-stage classical Hodgkin lymphoma (cHL) patients: results of pre-specified sub-group analyses from the ECHELON-1 study. Presented during EHA 2018; Abstract S112.

Spreker Martin Hutchings


Martin Hutchings, MD, PhD, Rigshospitalet, Copenhagen, Denmark


Zie: Keyslides


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