BRENTUXIMAB VEDOTIN WITH CHEMOTHERAPY FOR STAGE III/IV CLASSICAL HODGKIN LYMPHOMA: 4-YEAR UPDATE OF THE ECHELON-1 STUDY
Author(s): ,
Marco Picardi
Affiliations:
Hematology Unit,University Federico II,Naples,Italy
,
David J. Straus
Affiliations:
Department of Medicine, Lymphoma Service,Memorial Sloan Kettering Cancer Center,New York, NY,United States
,
Monika Długosz-Danecka
Affiliations:
Department of Clinical Oncology,Malopolskie Centrum Medyczne S.C,Krakow,Poland
,
Sergey Alekseev
Affiliations:
Petrov Research Institute of Oncology,St. Petersburg,Russian Federation
,
Arpad Illes
Affiliations:
University of Debrecen,Debrecen,Hungary
,
Ewa Lech-Maranda
Affiliations:
Department of Hematology,Institute of Hematology and Transfusion Medicine,Warsaw,Poland
,
Tatyana A. Feldman
Affiliations:
Hackensack University Medical Center,Hackensack, NJ ,United States
,
Piotr Smolewski
Affiliations:
Medical University of Lodz,Lodz,Poland
,
Kerry J. Savage
Affiliations:
BC Cancer Centre for Lymphoid Cancer,Vancouver, BC,Canada
,
Jan Walewski
Affiliations:
Maria Sklodowska-Curie Institute and Oncology Centre,Warsaw,Poland
,
Radhakrsihnan Ramchandren
Affiliations:
The University of Tennessee Graduate School of Medicine,Knoxville, TN,United States
,
Pier Luigi Zinzani
Affiliations:
Institute of Hematology 'Seragnoli',Bologna University,Bologna,Italy
,
Martin Hutchings
Affiliations:
Department of Haematology and Phase 1 Unit,Rigshospitalet,Copenhagen,Denmark
,
Joseph M. Connors
Affiliations:
BC Cancer Centre for Lymphoid Cancer,Vancouver, BC,Canada
,
John Radford
Affiliations:
Department of Medical Oncology, University of Manchester and the Christie NHS Foundation Trust,Manchester Academic Health Science Centre,Manchester,United Kingdom
,
Javier Munoz
Affiliations:
Banner MD Anderson Cancer Center,Gilbert, AZ,United States
,
Won-Seong Kim
Affiliations:
Division of Hematology-Oncology, Department of Internal Medicine,Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Korea, Republic Of
,
Ranjana Advani
Affiliations:
Department of Medicine, Division of Oncology,Stanford University,Stanford, CA,United States
,
Stephen M. Ansell
Affiliations:
Division of Hematology,Mayo Clinic,Rochester, MN,United States
,
Anas Younes
Affiliations:
Department of Medicine, Lymphoma Service,Memorial Sloan Kettering Cancer Center,New York, NY,United States
,
Andrea Gallamini
Affiliations:
Research Innovation and Statistics,Antoine-Lacassagne Cancer Centre,Nice,France
,
Harry Miao
Affiliations:
Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge, MA,United States
,
Rachel Liu
Affiliations:
Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge, MA,United States
,
Keenan Fenton
Affiliations:
Seattle Genetics, Inc.,Bothell, WA,United States
,
Andres Forero-Torres
Affiliations:
Seattle Genetics, Inc.,Bothell, WA,United States
Nancy L. Bartlett
Affiliations:
Washington University School of Medicine Siteman Cancer Center,St. Louis, MO,United States
(Abstract release date: 05/14/20) EHA Library. Picardi M. 06/12/20; 293624; EP1135
Marco Picardi
Marco Picardi
Contributions
Abstract

Abstract: EP1135

Type: e-Poster

Background
In the primary analysis of the international, phase 3 ECHELON-1 trial, the combination of brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (A+AVD) demonstrated a statistically significant improvement in modified progression-free survival (PFS) compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients (pts) with newly diagnosed Stage III or IV classical HL (cHL) (NCT01712490; Connors JM, et al. N Engl J Med 2018;378:331–44). The benefit of A+AVD in the ITT population observed in the primary analysis was maintained at a 3-year median follow-up [3-year PFS: A+AVD: 83.1% (95% CI: 79.9, 85.9), ABVD: 76% (95% CI: 72.4, 79.2)] and appears independent of interim PET status, disease stage, and prognostic risk factors. 

Aims
To present the results of the ECHELON-1 study at a median follow-up of 48.4 months. 

Methods
Newly diagnosed pts with Stage III or IV cHL were randomized 1:1 to receive A+AVD (n=664) or ABVD (n=670) intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. The primary endpoint of the study was modified PFS per independent central review. The extended follow-up PFS analysis is exploratory and per investigator assessment. Pts with ongoing peripheral neuropathy (PN) at end of treatment were followed for resolution or improvement (defined as improved by ≥1 grade from worst grade as of the latest assessment) during the post-treatment follow-up period.

Results
At this extended follow-up, treatment with A+AVD versus ABVD was associated with a 31% reduction in the risk of progression or death per investigator (HR 0.691, P=0.003; Table). Four-year PFS rates were 81.7% with A+AVD versus 75.1% with ABVD. A consistent improvement in PFS was observed for pts treated with A+AVD versus ABVD across subgroups, including Stage III and Stage IV disease, age (<60 and ≥60 years) extranodal sites (0,1, and >1), and International Prognostic Scores (IPS) (0–1, 2–3, and 4–7). Exploratory subgroup analyses of PFS in PET2(+) and PET2(-) pts showed a treatment effect in favor of A+AVD that was independent of PET2 status (Table). A total of 83% (365/442) of pts with PN in the A+AVD arm had either complete resolution (68%, 300/442) or improvement (15%, 65/442) compared with 84% (240/286) with either complete resolution (76%, 217/286) or improvement (8%, 23/286) in the ABVD arm. Among pts with ongoing PN after continued follow-up, the majority were Grade 1/2 events, with 88% (125/142; 59% Grade 1) and 94% (65/69; 65% Grade 1) in the A+AVD and ABVD arms, respectively. Overall survival data are not yet mature; per protocol, the final analysis will be performed after 112 deaths have occurred.

Conclusion
With a median follow-up of 48.4 months, A+AVD continues to provide a robust and durable benefit over ABVD for pts with previously untreated Stage III or IV cHL. The PFS benefit in favor of A+AVD is evident regardless of PET2 status, disease stage, age, and IPS. PN continued to completely resolve or improve in pts on the A+AVD and ABVD arms, with most pts achieving complete resolution of their symptoms. Together, these data further support the clinical advantages of A+AVD over ABVD as treatment for pts with previously untreated Stage III or IV cHL.

Session topic: 17. Hodgkin lymphoma - Clinical

Keyword(s): Hodgkin's lymphoma

Abstract: EP1135

Type: e-Poster

Background
In the primary analysis of the international, phase 3 ECHELON-1 trial, the combination of brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (A+AVD) demonstrated a statistically significant improvement in modified progression-free survival (PFS) compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients (pts) with newly diagnosed Stage III or IV classical HL (cHL) (NCT01712490; Connors JM, et al. N Engl J Med 2018;378:331–44). The benefit of A+AVD in the ITT population observed in the primary analysis was maintained at a 3-year median follow-up [3-year PFS: A+AVD: 83.1% (95% CI: 79.9, 85.9), ABVD: 76% (95% CI: 72.4, 79.2)] and appears independent of interim PET status, disease stage, and prognostic risk factors. 

Aims
To present the results of the ECHELON-1 study at a median follow-up of 48.4 months. 

Methods
Newly diagnosed pts with Stage III or IV cHL were randomized 1:1 to receive A+AVD (n=664) or ABVD (n=670) intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. The primary endpoint of the study was modified PFS per independent central review. The extended follow-up PFS analysis is exploratory and per investigator assessment. Pts with ongoing peripheral neuropathy (PN) at end of treatment were followed for resolution or improvement (defined as improved by ≥1 grade from worst grade as of the latest assessment) during the post-treatment follow-up period.

Results
At this extended follow-up, treatment with A+AVD versus ABVD was associated with a 31% reduction in the risk of progression or death per investigator (HR 0.691, P=0.003; Table). Four-year PFS rates were 81.7% with A+AVD versus 75.1% with ABVD. A consistent improvement in PFS was observed for pts treated with A+AVD versus ABVD across subgroups, including Stage III and Stage IV disease, age (<60 and ≥60 years) extranodal sites (0,1, and >1), and International Prognostic Scores (IPS) (0–1, 2–3, and 4–7). Exploratory subgroup analyses of PFS in PET2(+) and PET2(-) pts showed a treatment effect in favor of A+AVD that was independent of PET2 status (Table). A total of 83% (365/442) of pts with PN in the A+AVD arm had either complete resolution (68%, 300/442) or improvement (15%, 65/442) compared with 84% (240/286) with either complete resolution (76%, 217/286) or improvement (8%, 23/286) in the ABVD arm. Among pts with ongoing PN after continued follow-up, the majority were Grade 1/2 events, with 88% (125/142; 59% Grade 1) and 94% (65/69; 65% Grade 1) in the A+AVD and ABVD arms, respectively. Overall survival data are not yet mature; per protocol, the final analysis will be performed after 112 deaths have occurred.

Conclusion
With a median follow-up of 48.4 months, A+AVD continues to provide a robust and durable benefit over ABVD for pts with previously untreated Stage III or IV cHL. The PFS benefit in favor of A+AVD is evident regardless of PET2 status, disease stage, age, and IPS. PN continued to completely resolve or improve in pts on the A+AVD and ABVD arms, with most pts achieving complete resolution of their symptoms. Together, these data further support the clinical advantages of A+AVD over ABVD as treatment for pts with previously untreated Stage III or IV cHL.

Session topic: 17. Hodgkin lymphoma - Clinical

Keyword(s): Hodgkin's lymphoma

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