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IMPROVED OVERALL SURVIVAL WITH FIRST-LINE BRENTUXIMAB VEDOTIN PLUS CHEMOTHERAPY IN PATIENTS WITH STAGE III/IV CLASSICAL HODGKIN LYMPHOMA: 6-YEAR ANALYSIS OF ECHELON-1
Author(s): ,
Martin Hutchings
Affiliations:
Department of Haematology,Rigshospitalet, Copenhagen University Hospital,Copenhagen,Danemark;Department of Haematology,Rigshospitalet, Copenhagen University Hospital,Copenhagen,Dänemark;Department of Haematology,Rigshospitalet, Copenhagen University Hospital,Copenhagen,Danimarca;Department of Haematology,Rigshospitalet, Copenhagen University Hospital,Copenhagen,Danemark;Department of Haematology,R
,
Stephen M. Ansell
Affiliations:
Division of Hematology,Mayo Clinic,Rochester, MN,États-unis;Division of Hematology,Mayo Clinic,Rochester, MN,Vereinigte Staaten;Division of Hematology,Mayo Clinic,Rochester, MN,Stati Uniti;Division of Hematology,Mayo Clinic,Rochester, MN,United States;Division of Hematology,Mayo Clinic,Rochester, MN,Estados Unidos;Division of Hematology,Mayo Clinic,Rochester, MN,Verenigde Staten;Division of Hemato
,
David J. Straus
Affiliations:
Department of Medicine, Lymphoma Service,Memorial Sloan Kettering Cancer Center,New York, NY,États-unis;Department of Medicine, Lymphoma Service,Memorial Sloan Kettering Cancer Center,New York, NY,Vereinigte Staaten;Department of Medicine, Lymphoma Service,Memorial Sloan Kettering Cancer Center,New York, NY,Stati Uniti;Department of Medicine, Lymphoma Service,Memorial Sloan Kettering Cancer Center
,
Joseph M. Connors
Affiliations:
BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Canada;BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Kanada;BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Canada;BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Canada;BC Cancer Centre for Lymphoid Cancer and Dep
,
Won Seog Kim
Affiliations:
Division of Hematology-Oncology, Department of Internal Medicine,Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Corée, République De;Division of Hematology-Oncology, Department of Internal Medicine,Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Corea del Sud;Division of Hematology-Oncology, Department of Internal Medicine,Samsung Medical Center,
,
Andrea Gallamini
Affiliations:
Research and Innovation,Antoine-Lacassagne Cancer Centre,Nice,France;Research and Innovation,Antoine-Lacassagne Cancer Centre,Nice,Frankreich;Research and Innovation,Antoine-Lacassagne Cancer Centre,Nice,Francia;Research and Innovation,Antoine-Lacassagne Cancer Centre,Nice,France;Research and Innovation,Antoine-Lacassagne Cancer Centre,Nice,Francia;Research and Innovation,Antoine-Lacassagne Cancer
,
Radhakrishnan Ramchandren
Affiliations:
The University of Tennessee Graduate School of Medicine,Knoxville, TN,États-unis;The University of Tennessee Graduate School of Medicine,Knoxville, TN,Vereinigte Staaten;The University of Tennessee Graduate School of Medicine,Knoxville, TN,Stati Uniti;The University of Tennessee Graduate School of Medicine,Knoxville, TN,United States;The University of Tennessee Graduate School of Medicine,Knoxvill
,
Jonathan W. Friedberg
Affiliations:
James P. Wilmot Cancer Institute, University of Rochester Medical Center,Rochester, NY,États-unis;James P. Wilmot Cancer Institute, University of Rochester Medical Center,Rochester, NY,Vereinigte Staaten;James P. Wilmot Cancer Institute, University of Rochester Medical Center,Rochester, NY,Stati Uniti;James P. Wilmot Cancer Institute, University of Rochester Medical Center,Rochester, NY,United Sta
,
Ranjana Advani
Affiliations:
Department of Medicine, Division of Oncology,Stanford University,Stanford, CA,États-unis;Department of Medicine, Division of Oncology,Stanford University,Stanford, CA,Vereinigte Staaten;Department of Medicine, Division of Oncology,Stanford University,Stanford, CA,Stati Uniti;Department of Medicine, Division of Oncology,Stanford University,Stanford, CA,United States;Department of Medicine, Division
,
Andrew M. Evens
Affiliations:
Division of Blood Disorders,Rutgers Cancer Institute of New Jersey,New Brunswick, NJ,États-unis;Division of Blood Disorders,Rutgers Cancer Institute of New Jersey,New Brunswick, NJ,Vereinigte Staaten;Division of Blood Disorders,Rutgers Cancer Institute of New Jersey,New Brunswick, NJ,Stati Uniti;Division of Blood Disorders,Rutgers Cancer Institute of New Jersey,New Brunswick, NJ,United States;Divi
,
Piotr Smolewski
Affiliations:
Department of Experimental Hematology,Medical University of Lodz,Lodz,Pologne;Department of Experimental Hematology,Medical University of Lodz,Lodz,Polen;Department of Experimental Hematology,Medical University of Lodz,Lodz,Polonia;Department of Experimental Hematology,Medical University of Lodz,Lodz,Poland;Department of Experimental Hematology,Medical University of Lodz,Lodz,Polonia;Department of
,
Kerry J. Savage
Affiliations:
BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Canada;BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Kanada;BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Canada;BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology,Vancouver,Canada;BC Cancer Centre for Lymphoid Cancer and Dep
,
Nancy L. Bartlett
Affiliations:
Washington University School of Medicine Siteman Cancer Center,St Louis, MO,États-unis;Washington University School of Medicine Siteman Cancer Center,St Louis, MO,Vereinigte Staaten;Washington University School of Medicine Siteman Cancer Center,St Louis, MO,Stati Uniti;Washington University School of Medicine Siteman Cancer Center,St Louis, MO,United States;Washington University School of Medicine
,
Hyeon-Seok Eom
Affiliations:
Center for Hematologic Malignancy, National Cancer Center,Goyang,Corée, République De;Center for Hematologic Malignancy, National Cancer Center,Goyang,Corea del Sud;Center for Hematologic Malignancy, National Cancer Center,Goyang,South Korea,Republic;Center for Hematologic Malignancy, National Cancer Center,Goyang,Zuid Korea;Center for Hematologic Malignancy, National Cancer Center,Goyang,Repúblic
,
Jeremy S. Abramson
Affiliations:
Massachusetts General Hospital,Boston, MA,États-unis;Massachusetts General Hospital,Boston, MA,Vereinigte Staaten;Massachusetts General Hospital,Boston, MA,Stati Uniti;Massachusetts General Hospital,Boston, MA,United States;Massachusetts General Hospital,Boston, MA,Estados Unidos;Massachusetts General Hospital,Boston, MA,Verenigde Staten;Massachusetts General Hospital,Boston, MA,Estados Unidos;Mas
,
Cassie Dong
Affiliations:
Takeda Development Center Americas, Inc. (TDCA),Lexington MA,États-unis;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,Vereinigte Staaten;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,Stati Uniti;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,United States;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,Estados Unidos;Takeda Development Cente
,
Frank Campana
Affiliations:
Takeda Development Center Americas, Inc. (TDCA),Lexington MA,États-unis;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,Vereinigte Staaten;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,Stati Uniti;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,United States;Takeda Development Center Americas, Inc. (TDCA),Lexington MA,Estados Unidos;Takeda Development Cente
,
Keenan Fenton
Affiliations:
Seagen Inc.,Bothell, WA,États-unis;Seagen Inc.,Bothell, WA,Vereinigte Staaten;Seagen Inc.,Bothell, WA,Stati Uniti;Seagen Inc.,Bothell, WA,United States;Seagen Inc.,Bothell, WA,Estados Unidos;Seagen Inc.,Bothell, WA,Verenigde Staten;Seagen Inc.,Bothell, WA,Estados Unidos;Seagen Inc.,Bothell, WA,United States;Seagen Inc.,Bothell, WA,USA
,
Markus Puhlmann
Affiliations:
Seagen Inc.,Bothell, WA,États-unis;Seagen Inc.,Bothell, WA,Vereinigte Staaten;Seagen Inc.,Bothell, WA,Stati Uniti;Seagen Inc.,Bothell, WA,United States;Seagen Inc.,Bothell, WA,Estados Unidos;Seagen Inc.,Bothell, WA,Verenigde Staten;Seagen Inc.,Bothell, WA,Estados Unidos;Seagen Inc.,Bothell, WA,United States;Seagen Inc.,Bothell, WA,USA
John Radford
Affiliations:
The University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre,Manchester,Royaume-uni;The University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre,Manchester,Vereinigtes Königreich;The University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre,Manchester,Re
(Abstract release date: 05/26/22) EHA Library. Hutchings M. 06/10/22; 357064; S200
Martin Hutchings
Martin Hutchings
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S200

Type: Oral Presentation

Session title: Hodgkin lymphoma - Clinical

Background
In classical Hodgkin lymphoma (cHL), improved overall survival (OS) with first-line treatment using new combinations has seldom been observed compared with existing approaches. Five-year data from the randomized phase 3 ECHELON-1 study (NCT01712490) supported long-term progression-free survival (PFS) with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in patients (pts) with previously untreated stage III/IV cHL, regardless of interim positron emission tomography (PET) status. The long-term safety profile of A+AVD was manageable, and numerically fewer secondary malignancies were reported versus ABVD, as well as a greater number of pregnancies (Straus et al, Lancet Haematol 2021).

Aims
To report the pre-specified OS analysis from ECHELON-1, as well as relevant long-term safety data, after approximately 6 years of follow-up (cut-off June 1, 2021).

Methods
Pts were randomized 1:1 to receive up to 6 cycles of A+AVD (n=664) or ABVD (n=670) on day 1 and 15, every 28 days. PFS per investigator was reported for long-term follow-up. The key secondary end point was OS, which was an event-driven, pre-specified, alpha-controlled analysis in the intention-to-treat population, with a prespecified interim analysis after 103 deaths. Analysis of OS in prespecified subgroups was exploratory and was not adjusted for multiplicity. Informed consent was obtained for all pts.

Results
In total, 39 OS events in the A+AVD arm and 64 in the ABVD arm had occurred at a median follow-up of 73 months, significantly favoring A+AVD (hazard ratio [HR] 0.590; 95% CI 0.396–0.879; p=0.009). There was a consistent OS benefit for A+AVD vs ABVD across prespecified subgroups, including: stage III (HR: 0.863; 95% CI 0.452–1.648) and stage IV disease (HR: 0.478; 95% CI 0.286–0.799) at diagnosis, pts who were PET-negative at cycle 2 (PET2)-negative (HR: 0.583; 95% CI 0.338–0.856) and PET2-positive (HR: 0.163; 95% CI 0.037–0.717), pts aged <60 years (HR: 0.509; 95% CI 0.291–0.890), pts aged ≥60 years (HR: 0.829; 95% CI 0.469–1.466), and across all geographies, including Europe (HR: 0.783; 95% CI 0.467–1.315) and North America (HR: 0.327; 95% CI 0.153–0.699). The 6-year PFS estimate was 82.3% (79.1–85.0) vs 74.5% (70.8–77.7) with A+AVD vs ABVD, respectively (HR: 0.678; 95% CI: 0.532–0.863). The long-term safety profile of A+AVD was comparable to that of ABVD. In both A+AVD and ABVD groups, treatment-emergent peripheral neuropathy continued to resolve or improve, with 86% (379/443) and 87% (249/286) of cases in the A+AVD and ABVD arms either completely resolving (72% vs 79%) or improving (14% vs 8%) by last follow-up. Overall, 23 secondary malignancies in the A+AVD arm and 32 in the ABVD arm were reported. Pregnancies and live births were reported by a greater number of female pts in the A+AVD group vs the ABVD group (49 vs 28 and 42 vs 19, respectively) and there were no stillbirths reported during the study. There were no new safety signals.

Conclusion
There was a statistically significant 41% reduction in the risk of death with A+AVD vs ABVD, with a consistent OS benefit across prespecified subgroups. The long-term safety profile was manageable, consistent with prior reports. These data support A+AVD as a preferred option for previously untreated stage III and IV cHL.

Keyword(s): CD30, Chemotherapy, Clinical trial, Hodgkin's lymphoma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S200

Type: Oral Presentation

Session title: Hodgkin lymphoma - Clinical

Background
In classical Hodgkin lymphoma (cHL), improved overall survival (OS) with first-line treatment using new combinations has seldom been observed compared with existing approaches. Five-year data from the randomized phase 3 ECHELON-1 study (NCT01712490) supported long-term progression-free survival (PFS) with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in patients (pts) with previously untreated stage III/IV cHL, regardless of interim positron emission tomography (PET) status. The long-term safety profile of A+AVD was manageable, and numerically fewer secondary malignancies were reported versus ABVD, as well as a greater number of pregnancies (Straus et al, Lancet Haematol 2021).

Aims
To report the pre-specified OS analysis from ECHELON-1, as well as relevant long-term safety data, after approximately 6 years of follow-up (cut-off June 1, 2021).

Methods
Pts were randomized 1:1 to receive up to 6 cycles of A+AVD (n=664) or ABVD (n=670) on day 1 and 15, every 28 days. PFS per investigator was reported for long-term follow-up. The key secondary end point was OS, which was an event-driven, pre-specified, alpha-controlled analysis in the intention-to-treat population, with a prespecified interim analysis after 103 deaths. Analysis of OS in prespecified subgroups was exploratory and was not adjusted for multiplicity. Informed consent was obtained for all pts.

Results
In total, 39 OS events in the A+AVD arm and 64 in the ABVD arm had occurred at a median follow-up of 73 months, significantly favoring A+AVD (hazard ratio [HR] 0.590; 95% CI 0.396–0.879; p=0.009). There was a consistent OS benefit for A+AVD vs ABVD across prespecified subgroups, including: stage III (HR: 0.863; 95% CI 0.452–1.648) and stage IV disease (HR: 0.478; 95% CI 0.286–0.799) at diagnosis, pts who were PET-negative at cycle 2 (PET2)-negative (HR: 0.583; 95% CI 0.338–0.856) and PET2-positive (HR: 0.163; 95% CI 0.037–0.717), pts aged <60 years (HR: 0.509; 95% CI 0.291–0.890), pts aged ≥60 years (HR: 0.829; 95% CI 0.469–1.466), and across all geographies, including Europe (HR: 0.783; 95% CI 0.467–1.315) and North America (HR: 0.327; 95% CI 0.153–0.699). The 6-year PFS estimate was 82.3% (79.1–85.0) vs 74.5% (70.8–77.7) with A+AVD vs ABVD, respectively (HR: 0.678; 95% CI: 0.532–0.863). The long-term safety profile of A+AVD was comparable to that of ABVD. In both A+AVD and ABVD groups, treatment-emergent peripheral neuropathy continued to resolve or improve, with 86% (379/443) and 87% (249/286) of cases in the A+AVD and ABVD arms either completely resolving (72% vs 79%) or improving (14% vs 8%) by last follow-up. Overall, 23 secondary malignancies in the A+AVD arm and 32 in the ABVD arm were reported. Pregnancies and live births were reported by a greater number of female pts in the A+AVD group vs the ABVD group (49 vs 28 and 42 vs 19, respectively) and there were no stillbirths reported during the study. There were no new safety signals.

Conclusion
There was a statistically significant 41% reduction in the risk of death with A+AVD vs ABVD, with a consistent OS benefit across prespecified subgroups. The long-term safety profile was manageable, consistent with prior reports. These data support A+AVD as a preferred option for previously untreated stage III and IV cHL.

Keyword(s): CD30, Chemotherapy, Clinical trial, Hodgkin's lymphoma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.

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