Highlights from

EHA 2019

European Hematology Association

Amsterdam 13-16 June 2019

Brentuximab vedotin continues to demonstrate superior clinical activity in classical Hodgkin lymphoma

Additional analysis and 3-year update of results from ECHELON-1, a frontline phase 3 trial evaluating brentuximab vedotin in combination with adriamycin, vinblastine, and dacarbazine (AVD) compared with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in stage III or IV frontline classical Hodgkin lymphoma (HL) patients, resulted in a statistically significant improvement in modified progression-free survival (PFS) for the brentuximab vedotin + AVD arm vs the control arm of ABVD, as assessed by independent review.

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, a defining marker of classical HL and expressed on the surface of several types of peripheral T-cell lymphomas. “Tumour expression of CD30 by IHC in B-cell and T-cell non-Hodgkin lymphomas can be quite variable between different patients with the same diagnosis and even between different biopsies within the same patient,” said Dr Steven Horwitz, (Memorial Sloan Kettering Cancer Center, USA). “Results of the analysis suggest that a lower limit or threshold of CD30 expression required for efficacy has not been identified and individual patients may experience clinical benefit from brentuximab vedotin regardless of the level of CD30 expression.”

The analysis examined PFS outcomes per investigator assessment in the intent-to-treat population of 1,334 patients at 3-years by cycle 2 positron-emission tomography (PET2) status in patients <60 years old. The ECHELON-1 trial achieved its primary endpoint with the combination of brentuximab vedotin plus AVD resulting in a statistically significant improvement in modified PFS vs the control arm of ABVD as assessed by independent review facility (HR 0.77; P=0.035). Modified PFS was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy per independent review facility followed by subsequent anticancer therapy. Key findings from this updated analysis include:

  • The 3-year PFS for all patients in the brentuximab vedotin + AVD arm was 83.1% compared with 76% in the ABVD arm (HR 0.70), a difference of 7.1%.
  • PFS benefit at 3-years for brentuximab vedotin + AVD was observed for all patients independent of PET2 status, including in patients <60 years old.
  • o PET2-negative result was 85.8% in the brentuximab vedotin + AVD arm compared with 79.5% in the ABVD arm (HR 0.69), a difference of 6.3%.
  • o PET2-positive result was 67.7% in the brentuximab vedotin + AVD arm compared with 51.5% in the ABVD arm (HR 0.59), a difference of 16.2%.
  • Consistent improvement in PFS was observed among patients treated with brentuximab vedotin + AVD compared with ABVD across the majority of pre-specified subgroups, including disease stage, age, and prognostic score.
  • In the brentuximab vedotin + AVD arm, peripheral neuropathy events were observed in 67% of patients compared with 43% in the ABVD arm. The 3-year analysis shows that among patients with peripheral neuropathy, 78% of in the brentuximab vedotin + AVD arm and 83% in the ABVD arm reported complete resolution or improvement at last follow-up.
  1. Harowitz S et al. Brentuximab vedotin with chemotherapy for stage 3/4 classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study. Abstract S820, 24th Congress of the European Hematology Association, 13-16 June 2019, Amsterdam, the Netherlands.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.