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Illidge, T.1; Pro, B.2; Trümper, L.3; O'Connor, O. A.4; Advani, R.5; Iyer, S.6; Bartlett, N. L.7; Christensen, J. H.8; Morschhauser, F.9; Domingo-Domenech, E.10; Rossi, G.11; Kim, Seog W.12; Feldman, T.13; Lennard, A.14; Belada, D.15; Illes, A.16; Tobinai, K.17; Tsukasaki, K.18; Yeh, S.-P.19; Hüttmann, A.20; Savage, K. J.21; Shustov, A.22; Yuen, S.23; Zinzani, P. L.24; Little, M.25; Manley, T.26; Rao, S.26; Fanale, M.26; Horwitz, S.27

doi: 10.1097/01.HS9.0000562572.63485.4f
Poster Session II: Aggressive non-Hodgkin lymphoma - Clinical

1Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, NIHR Biomedical Research Centre, Manchester Academic Health Sciences Centre, Christie Hospital NHS Foundation Trust, Manchester, United Kingdom

2Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States

3Universitätsmedizin Göttingen, Göttingen, Germany

4Columbia University Medical Center, New York

5Stanford Cancer Center, Blood and Marrow Transplant Program, Stanford

6MD Anderson Cancer Center/University of Texas, Houston

7Washington University School of Medicine, St. Louis, United States

8Odense University Hospital, Odense, Denmark

9CHRU de Lille, Lille cedex, Nord-Pas-de-Calais, France

10Institut Catala D'oncologia, L'Hospitalet de Llobregat, Barcelona, Spain

11Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy

12Samsung Medical Center, Seoul, Korea, Republic Of

13Hackensack University Medical Center, Hackensack, United States

14Freeman Hospital, Newcastle upon Tyne, United Kingdom

154th Department of Internal Medicine - Hematology, University Hospital Hradec Králové, Czech Republic and Charles University in Prague, Faculty of Medicine, Hradec Kralove, Czech Republic

16Debreceni Egyetem, Debrecen, Hungary

17National Cancer Center Hospital, Tokyo

18Saitama Medical University International Medical Center, Saitama, Japan

19China Medical University Hospital, Taichung, Taiwan, Republic of China

20Universitatsklinikum Essen, Essen, Germany

21University of British Columbia and the Department of Medical Oncology, British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, Canada

22University of Washington Medical Center, Seattle, United States

23Calvary Mater Newcastle Hospital, Newcastle, Australia

24Institute of Hematology “Seràgnoli” University of Bologna, Bologna, Italy

25Takeda Pharmaceuticals International Company, Cambridge

26Seattle Genetics, Inc., Bothell

27Memorial Sloan Kettering Cancer Center, Basking Ridge, United States

Please indicate where the abstract has been published before: The data in this abstract have been published in the Lancet (Horwitz 2019).

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Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphoma (NHL) accounting for approximately 10% of all NHL cases worldwide, with a higher incidence reported in certain Asian countries. The most common frontline regimen for PTCL is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens; however, anthracycline-containing regimens result in a low rate of complete remission (CR) (Savage K, et al. Ann Oncol 2004). Based on the encouraging activity and manageable safety profile observed in a phase 1 study (Fanale M, et al. Blood 2018), the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP for the treatment of CD30-positive PTCL.

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To compare the effects of frontline brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP as frontline therapy in patients with CD30-positive peripheral T-cell lymphoma (PTCL).

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ECHELON-2 ( No. NCT01777152) is a phase 3, randomized, double blind, double-dummy, placebo controlled, active-comparator, multicenter study. Eligible adults with previously-untreated CD30-positive PTCL (targeting 75% ± 5% with systemic anaplastic large cell lymphoma [sALCL]) were randomized 1:1 to receive either A+CHP or CHOP for 6 or 8 21-day cycles. Randomization was stratified by histological subtype as per local pathology assessment and by international prognostic index (IPI) score. The primary endpoint, progression free survival (PFS) per blinded independent central review (BICR), was analyzed for the intent-to-treat population. Key secondary endpoints were overall survival (OS), PFS in sALCL, CR rate, and objective response rate (ORR). Consolidative stem cell transplantation or radiotherapy was permitted at the investigator's discretion after end of treatment.

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A total of 452 patients were enrolled between January 2013 and November 2016 and 226 patients were randomly assigned to each arm. Overall, the median age was 58 years (range, 18 to 85). The study enrolled patients with advanced disease (Stage III [27%] and Stage IV [53%]; IPI ≥2 [78%]) and most patients (316 patients [70%]) had sALCL (218 patients [48%] anaplastic lymphoma kinase [ALK]-negative and 98 patients [22%] ALK-positive). The hazard ratios of both PFS (0.71 [95% confidence interval {CI}: 0.54, 0.93], P = 0.01) and the OS (0.66 [95% CI: 0.46, 0.95], P = 0.02) favored A+CHP over CHOP. The median PFS was 48.2 months (95% CI: 35.2, not evaluable) versus 20.8 months (95% CI: 12.7, 47.6) for A+CHP and CHOP, respectively. The 3-year PFS was 57.1% (95% CI: 49.9, 63.7) for A+CHP compared with 44.4% (95% CI: 37.6, 50.9) for CHOP. Median OS was not reached for either arm. Adverse events (AEs), including incidence and severity of neutropenia and peripheral neuropathy, were similar between arms. AEs leading to death occurred in 7 patients (3%) in the A+CHP arm and 9 patients (4%) in the CHOP arm.



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Frontline treatment with A+CHP is superior to CHOP for patients with CD30-positive PTCL as demonstrated by a statistically significant improvement in PFS and OS, with a manageable safety profile.

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