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

List of authors.
  • Stephen M. Ansell, M.D., Ph.D.,
  • John Radford, M.D.,
  • Joseph M. Connors, M.D.,
  • Monika Długosz-Danecka, M.D., Ph.D.,
  • Won-Seog Kim, M.D.,
  • Andrea Gallamini, M.D.,
  • Radhakrishnan Ramchandren, M.D.,
  • Jonathan W. Friedberg, M.D.,
  • Ranjana Advani, M.D.,
  • Martin Hutchings, Ph.D.,
  • Andrew M. Evens, D.O.,
  • Piotr Smolewski, M.D., Ph.D.,
  • Kerry J. Savage, M.D.,
  • Nancy L. Bartlett, M.D.,
  • Hyeon-Seok Eom, M.D., Ph.D.,
  • Jeremy S. Abramson, M.D.,
  • Cassie Dong, Ph.D.,
  • Frank Campana, M.D.,
  • Keenan Fenton, M.D.,
  • Markus Puhlmann, M.D.,
  • and David J. Straus, M.D.
  • for the ECHELON-1 Study Group*

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

Download a PDF of the Research Summary.

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.)

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Brentuximab Vedotin in Advanced Hodgkin’s Lymphoma
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Funding and Disclosures

Supported by Takeda Development Center Americas and Seagen.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Drs. Ansell and Radford contributed equally to this article.

This article was published on July 13, 2022, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank the patients who participated in this trial and their families; the staff at all the trial clinical sites; the members of the independent data and safety monitoring committee and the independent review committee; Michael Harrison, Pharm.D., for assistance with data review and interpretation; and Hedley Coppock, Ph.D., and Clair Clowes, M.Phil., both of Ashfield MedComms, an Ashfield Health company, for providing medical writing assistance with an earlier version of the manuscript.

Author Affiliations

From the Division of Hematology, Mayo Clinic, Rochester, MN (S.M.A.); the University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom (J.R.); BC Cancer Centre for Lymphoid Cancer, Vancouver (J.M.C., K.J.S.); Maria Sklodowska-Curie National Research Institute of Oncology, Krakow (M.D.-D.), and the Department of Experimental Hematology, Medical University of Lodz, Lodz (P.S.) — both in Poland; the Division of Hematology–Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (W.-S.K.), and the Department of Hematology–Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang (H.-S.E.) — both in South Korea; Research and Innovation Department, Antoine-Lacassagne Cancer Center, Nice, France (A.G.); the University of Tennessee Graduate School of Medicine, Knoxville (R.R.); Wilmot Cancer Institute, University of Rochester, Rochester (J.W.F.), and the Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York (D.J.S.) — both in New York; the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA (R.A.); the Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen (M.H.); the Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick (A.M.E.); Washington University School of Medicine Siteman Cancer Center, St. Louis (N.L.B.); Massachusetts General Hospital, Boston (J.S.A.), and Takeda Development Center Americas, Lexington (C.D., F.C.) — both in Massachusetts; and Seagen, Bothell, WA (K.F., M.P.).

Dr. Ansell can be contacted at or at the Division of Hematology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55902.

The full list of the investigators in the ECHELON-1 Study Group was included with an earlier published trial; see the Supplementary Appendix, available at NEJM.org, for detailed information.