The combination of brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (A+AVD) may improve 3-year progression-free survival (PFS) in patients with stage III or IV classical Hodgkin lymphoma (cHL) compared with patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), according to updated results of the ECHELON-1 study (ClinicalTrials.gov Identifier: NCT01712490).1

ECHELON-1 is a multinational, open-label, randomized phase 3 trial comparing A+AVD with ABVD as frontline therapy for patients with stage III or IV cHL.2 In the original study, 1334 patients with stage III/IV cHL were randomly assigned to receive 6 cycles of A+AVD (664 patients) or ABVD (670 patients), as well as an interim positron emission tomography scan after cycle 2 (PET2).1,2 The updated results, which were published in Blood, included an exploratory analysis of 3-year PFS per investigator.1

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Most patients in both arms had a negative PET2 scan, including 89% of patients in the A+AVD arm and 86% of patients in the ABVD arm.1 Positive PET2 status was detected in 7% of patients in the A+AVD arm and 9% of patients in the ABVD arm; a small fraction of patients had unknown or unavailable status, including 4% of patients in the A+AVD arm and 5% of patients in the ABVD arm.1

After median follow-up of 37 months (range, 0.0-66.9), the 3-year PFS rate was higher in the A+AVD arm (83.1%; 95% CI, 79.9%-85.9%) compared with the ABVD arm (76.0%; 95% CI, 72.4%-79.2%), yielding a hazard ratio (HR) of 0.704 (95% CI, 0.55-0.90; P =.005).1

In patients younger than 60 years who had a negative PET2 scan, the 3-year PFS rate was 87.2% (95% CI, 83.9%-89.9%) in the A+AVD arm and 81.0% (95% CI, 77.1%-84.4%) in the ABVD arm (HR, 0.71; 95% CI, 0.51-0.98; P =.034).1 The investigators also noted a beneficial, but not statistically significant, trend in the PET2-positive patients within this subgroup; the 3-year PFS rate was 69.2% (95% CI, 54.1%-80.1%) in the A+AVD arm compared with 54.7% (95% CI, 40.0%-67.2%) in the ABVD arm (HR, 0.60; 95% CI, 0.32-1.15; P =.117).1

The A+AVD adverse events profile was previously reported to be consistent with that of the individual components of the regimen.1,2 In the updated report, the team noted more frequent complete resolution or improvement of symptoms in patients with peripheral neuropathy in the A+AVD arm compared with the ABVD arm (78% vs 83%).1

“These data further support the advantages of A+AVD [compared with] ABVD as frontline treatment of patients with advanced stage III or IV cHL,” the researchers concluded.

References

1. Straus DJ, Długosz-Danecka M, Alekseev S, et al. Brentuximab vedotin with chemotherapy for Stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study [published online January 16, 2020]. Blood. doi:10.1182/blood.2019003127

2. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:331-344. doi:10.1056/NEJMoa1708984