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Gallamini, A.1; Straus, D.2; Dlugosz-Danecka, M.3; Alekseev, S.4; Illes, A.5; Picardi, M.6; Lech-Maranda, E.7; Feldman, T.8; Smolewski, P.9; Savage, K.10; Bartlett, N.11; Walewski, J.12; Ramchandren, R.13; Zinzani, P.14; Connors, J.10; Jolin, H.15; Liu, R.15; Fenton, K.16; Josephson, N.16; Radford, J.17

doi: 10.1097/01.HS9.0000561560.35825.0d
Simultaneous Sessions II: Hodgkin lymphoma - Clinical

1Research, Innovation and Statistics, Antoine Lacassagne Cancer Center, Nice, France

2Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States

3Department of Hematology, Jagiellonian University, Krakow, Poland

4N.N. Petrov Scientific Research Institute of Oncology, St Petersburg, Russian Federation

5Department of Hematology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

6Department of Advanced Biomedical Science, Federico II University Hospital, Naples, Italy

7Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland

8John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, United States

9Department of Experimental Hematology, Medical University of Lodz, Lodz, Poland

10University of British Columbia and the Department of Medical Oncology, BC Cancer Centre for Lymphoid Cancer, Vancouver, Canada

11Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, United States

12Department of Lymphoid Malignancy, The Maria Sklodowska-Curie Institute and Oncology Center, Warsaw, Poland

13Department of Hematology-Oncology, Barbara Ann Karmanos Cancer Center, Detroit, United States

14Institute of Hematology Seragnoli, University of Bologna, Bologna, Italy

15Millennium Pharmaceuticals, Inc., Cambridge

16Seattle Genetics, Inc., Bothell, United States

17University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom

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The phase 3 ECHELON-1 study (NCT01712490) demonstrated that brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (A+AVD) was superior to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in terms of modified progression-free survival (PFS) per independent review and per investigator, for the frontline treatment of stage 3/4 classical Hodgkin lymphoma (cHL) (Connors JM, et al. N Engl J Med 2018;378: 331-344). The RATHL, and SWOG S0816 studies utilized positron-emission tomography (PET) scan-adapted strategies performed after cycle 2 (PET2), demonstrating short- and long-term toxicities in PET2-positive (PET2+) patients switched to bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), or escalated BEACOPP, and frequent relapses in PET2-negative (PET2-) patients. Long-term follow-up of patients with stage 3/4 disease who were aged ≤60 years in the RATHL and SWOG S0816 studies demonstrated 3-year PFS of 79.8% (PET2-, 82.1%), and 5-year PFS of 74% (PET2-, 76%), respectively.

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Here we present a 3-year update of the ECHELON-1 study to compare the effects of frontline A+AVD vs ABVD in patients with stage 3/4 cHL, including PFS per investigator and outcomes by PET status for the intention-to-treat (ITT) population.

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Patients with stage 3/4 cHL were randomized 1:1 to receive up to six cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was conducted, patients with Deauville score of 5 at PET2 were allowed to switch to an alternative therapy. All analyses of PFS are exploratory and per investigator assessment.

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At a median follow-up of 37 months, analysis of PFS in the ITT population favored the A+AVD treatment arm (Table), with a 3-year PFS of 83.1% for A+AVD vs 76.0% for ABVD; the 3-year PFS values for PET2- patients aged <60 years were 87.2% vs 81.0%, respectively. A trend toward benefit for PET2+ patients aged <60 years treated with A+AVD was also observed, with a 3-year PFS of 69.2% vs 54.7% with ABVD.

Data from subgroups, together with safety follow-up, including for peripheral neuropathy, will be presented.



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Follow-up at 3 years demonstrates that frontline treatment of stage 3/4 cHL with A+AVD provides a durable treatment benefit compared with ABVD that is independent of PET2 status. While direct comparisons cannot be made, efficacy with A+AVD appears favorable in the context of findings with PET-adapted strategies, without requiring interim PET assessment, escalation of therapy, or bleomycin.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.