THE ECHELON-2 TRIAL: RESULTS OF A RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDY OF BRENTUXIMAB VEDOTIN AND CHP (A+CHP) VERSUS CHOP IN FRONTLINE TREATMENT OF PATIENTS WITH CD30+ PERIPHERAL T-CELL LYMPHOMAS
Author(s): ,
Tim Illidge
Affiliations:
Division 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
,
Barbara Pro
Affiliations:
Division of Hematology and Oncology, Department of Medicine,Northwestern University Feinberg School of Medicine,Chicago,United States
,
Lorenz Trümper
Affiliations:
Universitätsmedizin Göttingen,Göttingen,Germany
,
Owen A O’Connor
Affiliations:
Columbia University Medical Center,New York,United States
,
Ranjana Advani
Affiliations:
Stanford Cancer Center, Blood and Marrow Transplant Program,Stanford,United States
,
Swaminathan Iyer
Affiliations:
MD Anderson Cancer Center/University of Texas,Houston,United States
,
Nancy L Bartlett
Affiliations:
Washington University School of Medicine,St. Louis,United States
,
Jacob Haaber Christensen
Affiliations:
Odense University Hospital,Odense,Denmark
,
Frank Morschhauser
Affiliations:
CHRU de Lille, Lille cedex,Nord-Pas-de-Calais,France
,
Eva Domingo-Domenech
Affiliations:
Institut Catala D'oncologia, L'Hospitalet de Llobregat,Barcelona,Spain
,
Giuseppe Rossi
Affiliations:
Azienda Ospedaliera Spedali Civili di Brescia,Brescia,Italy
,
Won Seog Kim
Affiliations:
Samsung Medical Center,Seoul,Korea, Republic Of
,
Tatyana Feldman
Affiliations:
Hackensack University Medical Center,Hackensack,United States
,
Anne Lennard
Affiliations:
Freeman Hospital,Newcastle upon Tyne,United Kingdom
,
David Belada
Affiliations:
4th Department of Internal Medicine - Hematology,University Hospital Hradec Králové, Czech Republic and Charles University in Prague, Faculty of Medicine,Hradec Kralove,Czech Republic
,
Arpad Illes
Affiliations:
Debreceni Egyetem,Debrecen,Hungary
,
Kensei Tobinai
Affiliations:
National Cancer Center Hospital,Tokyo,Japan
,
Kunihiro Tsukasaki
Affiliations:
Saitama Medical University International Medical Center,Saitama,Japan
,
Su-Peng Yeh
Affiliations:
China Medical University Hospital,Taichung,Taiwan, Province of China
,
Andreas Hüttmann
Affiliations:
Universitatsklinikum Essen,Essen,Germany
,
Kerry J Savage
Affiliations:
University of British Columbia and the Department of Medical Oncology, British Columbia Cancer Centre for Lymphoid Cancer,Vancouver,Canada
,
Andrei Shustov
Affiliations:
University of Washington Medical Center,Seattle,United States
,
Sam Yuen
Affiliations:
Calvary Mater Newcastle Hospital,Newcastle,Australia
,
Pier Luigi Zinzani
Affiliations:
Institute of Hematology “Seràgnoli” University of Bologna,Bologna,Italy
,
Meredith Little
Affiliations:
Takeda Pharmaceuticals International Company,Cambridge,United States
,
Thomas Manley
Affiliations:
Seattle Genetics, Inc.,Bothell,United States
,
Shangbang Rao
Affiliations:
Seattle Genetics, Inc.,Bothell,United States
,
Michelle Fanale
Affiliations:
Seattle Genetics, Inc.,Bothell,United States
Steven Horwitz
Affiliations:
Memorial Sloan Kettering Cancer Center,Basking Ridge,United States
EHA Library. Illidge T. Jun 15, 2019; 266687; PS1070
Tim Illidge
Tim Illidge
Contributions
Abstract

Abstract: PS1070

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background

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.

Aims

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).

Methods

ECHELON-2 (ClinicalTrials.gov 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.

Results

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.

Conclusion

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.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): CD30, Non-Hodgkin's lymphoma, Peripheral T-cell lymphoma, Phase III

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