Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma

Stephen M Ansell, John Radford, Joseph M Connors, Monika Długosz-Danecka, Won-Seog Kim, Andrea Gallamini, Radhakrishnan Ramchandren, Jonathan W Friedberg, Ranjana Advani, Andrew M Evens, Piotr Smolewski, Kerry J Savage, Nancy L Bartlett, Hyeon-Seok Eom, Jeremy S Abramson, Cassie Dong, Frank Campana, Keenan Fenton, Markus Puhlmann, David J StrausECHELON-1 Study Group, Martin Hutchings

106 Citations (Scopus)

Abstract

BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.

METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.

RESULTS: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.

CONCLUSIONS: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).

Original languageEnglish
JournalThe New England journal of medicine
Volume387
Issue number4
Pages (from-to)310-320
Number of pages11
ISSN0028-4793
DOIs
Publication statusPublished - 28 Jul 2022

Keywords

  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Bleomycin/adverse effects
  • Brentuximab Vedotin/adverse effects
  • Dacarbazine/adverse effects
  • Disease-Free Survival
  • Doxorubicin/adverse effects
  • Hodgkin Disease/drug therapy
  • Humans
  • Male
  • Neoplasm Staging
  • Testicular Neoplasms
  • Treatment Outcome
  • Vinblastine/adverse effects

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