Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study

David J. Straus, Monika Długosz-Danecka, Sergey Alekseev, Árpád Illés, Marco Picardi, Ewa Lech-Maranda, Tatyana Feldman, Piotr Smolewski, Kerry J. Savage, Nancy L. Bartlett, Jan Walewski, Radhakrishnan Ramchandren, Pier Luigi Zinzani, Martin Hutchings, Joseph M. Connors, John Radford, Javier Munoz, Won Seog Kim, Ranjana Advani, Stephen M. AnsellAnas Younes, Harry Miao, Rachael Liu, Keenan Fenton, Andres Forero-Torres, Andrea Gallamini

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) exhibited superior modified progression-free survival Skip (PFS) tovs Main doxorubicin, Content bleomycin, vinblastine, and dacarbazine (ABVD) for frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL). Maturing positron emission tomography (PET)-adapted trial data highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET scan after cycle 2 (PET2)-negative (PET2) patients. We present an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. A total of 1334 patients with stage III or IV cHL were randomized 1:1 to receive 6 cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was required. At median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2 patients aged <60 years were 87.2% vs 81.0%, respectively. A beneficial trend in PET2+ patients aged <60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% vs 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL, consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or bleomycin exposure. This trial was registered at www.clinicaltrials.gov as #NCT01712490 (EudraCT no. 2011-005450-60).

Original languageEnglish (US)
Pages (from-to)735-742
Number of pages8
JournalBlood
Volume135
Issue number10
DOIs
StatePublished - Mar 5 2020

Keywords

  • Clinical Trials and Observations
  • Lymphoid Neoplasia

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Straus, D. J., Długosz-Danecka, M., Alekseev, S., Illés, Á., Picardi, M., Lech-Maranda, E., Feldman, T., Smolewski, P., Savage, K. J., Bartlett, N. L., Walewski, J., Ramchandren, R., Zinzani, P. L., Hutchings, M., Connors, J. M., Radford, J., Munoz, J., Kim, W. S., Advani, R., ... Gallamini, A. (2020). Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study. Blood, 135(10), 735-742. https://doi.org/10.1182/BLOOD.2019003127