Brentuximab Vedotin plus Chemotherapy in High Risk Advanced-Stage Hodgkin Lymphoma (HL) Patients: Results of Pre-Specified Sub-group Analyses from the ECHELON-1 Study

Research output: Contribution to conferenceAbstract


Background: Primary results of the randomized, phase 3, ECHELON-1 study demonstrated a significant improvement in modified progression-free survival (mPFS), per independent review facility (IRF), in patients with advanced HL treated with frontline A+AVD vs doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD). At 2 years, the Hazard Ratio [HR] was 0.77 (95% CI: 0.60 to 0.98; p=0.04) and mPFS rates were 82.1% (95% CI, 78.8 to 85.0) vs 77.2% (95% CI, 73.7 to 80.4), respectively, a 4.9% point difference. We report data from pre-specified subgroups of the ECHELON-1 data.

Aims: This prespecified subanalysis assessed the efficacy and safety of A+AVD vs ABVD in patients with HL and high risk features including: ≥1 extranodal site of involvement, stage IV disease, and an International Prognostic Factor Project (IPFP) score of 4–7. 
Methods: Patients were randomized 1:1 to receive up to six 28-day cycles of A+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. Patients were analyzed by Stage at diagnosis (III vs IV), IPFP score (0–1 vs 2–3 vs 4–7), and number of extranodal disease sites (0 vs 1 vs ≥1). The primary endpoint of these subanalyses was mPFS (defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy).
Results: In total, 664 and 670 patients were randomized to A+AVD and ABVD, respectively. High risk features at baseline were well balanced between treatment group with 64% and 63% having stage IV disease, 25% and 27% having an IFPF Score of 4–7 in the A+AVD and ABVD arms respectively, 62% in each arm had ≥1 extranodal sites at baseline. A+AVD showed improved mPFS compared with ABVD in the following sub-groups (Table): stage IV disease (2-year PFS 82.0% vs 75.3% [HR=0.71, 95% CI: 0.53–0.96; p=0.023]), >1 extranodal sites (2-year PFS 80.2% vs 71.1% [HR=0.67, 95% CI: 0.44–1.00; p=0.049]) add ≥1 EN data. Patients with an IFPF score of 4–7 also had a favorable improvement in mPFS with A+AVD (77.0% vs 69.2% [HR=0.70, 95% CI: 0.46–1.07; p=0.097]). Efficacy and safety analyses for combinations of high risk sub-groups will be presented in full.
Conclusions: Compared with standard ABVD, A+AVD in frontline trends favorably for mPFS outcomes for patients with high risk HL (Stage IV disease, or ≥1 extranodal disease sites, or IFPF score of 4–7). These results suggest that patients with high risk HL might have a greater treatment benefit with A+AVD compared with ABVD.
Table. mPFS by patient sub-groups
Baseline characteristics                       A+AVD vs ABVD Hazard Ratio (95% CI)
Ann Arbor stage              Stage III            0.92 (0.60–1.42) p=0.712
                                       Stage IV            0.71 (0.53–0.96) p=0.023
IFPF score                        0–1                   0.84 (0.47–1.49) p=0.548
                                       2–3                   0.79 (0.55–1.12) p=0.183
                                       4–7                   0.70 (0.46–1.07) p=0.097
Extranodal sites               0                      1.04 (0.67–1.62) p=0.856
                                        1                      0.75 (0.48–1.16) p=0.191
                                        >1                    0.67 (0.44–1.00) p=0.049

Original languageEnglish
Publication statusUnpublished - 14 Feb 2018
EventEuropean Hematology Association - 23rd Congress - Stockholm, Sweden
Duration: 14 Jun 201817 Jun 2018


ConferenceEuropean Hematology Association - 23rd Congress


  • Hodgkin lymphoma
  • high risk
  • CD30
  • clinical trial


Dive into the research topics of 'Brentuximab Vedotin plus Chemotherapy in High Risk Advanced-Stage Hodgkin Lymphoma (HL) Patients: Results of Pre-Specified Sub-group Analyses from the ECHELON-1 Study'. Together they form a unique fingerprint.

Cite this