Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced-stage, classical Hodgkin lymphoma: A prespecified subgroup analysis of high-risk patients from the ECHELON-1 study

Hematol Oncol. 2021 Apr;39(2):185-195. doi: 10.1002/hon.2838. Epub 2021 Feb 16.

Abstract

Approximately one-third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high-risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON-1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first-line therapy after a median follow-up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD-treated versus ABVD-treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high-risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON-1 shows a favorable benefit-risk balance in high-risk patients.

Keywords: ECHELON-1; brentuximab vedotin; high risk Hodgkin lymphoma.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brentuximab Vedotin / pharmacology
  • Brentuximab Vedotin / therapeutic use*
  • Dacarbazine / pharmacology
  • Dacarbazine / therapeutic use*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Female
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging / methods*
  • Risk Factors
  • Vinblastine / pharmacology
  • Vinblastine / therapeutic use*

Substances

  • Vinblastine
  • Dacarbazine
  • Brentuximab Vedotin
  • Doxorubicin