Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study
Andrew M. Evens,
Joseph M. Connors,
Anas Younes,
Stephen M. Ansell,
Won Seog Kim,
John Radford,
Tatyana Feldman,
Joseph Tuscano,
Kerry J. Savage,
Yasuhiro Oki,
Andrew Grigg,
Christopher Pocock,
Monika Dlugosz-Danecka,
Keenan Fenton,
Andres Forero-Torres,
Rachael Liu,
Hina Jolin,
Ashish Gautam,
Andrea Gallamini
Affiliations
Andrew M. Evens
Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
Joseph M. Connors
BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology, Vancouver
Anas Younes
Memorial Sloan Kettering Cancer Center, NY
Stephen M. Ansell
Mayo Clinic, Rochester, NY
Won Seog Kim
Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul
John Radford
University of Manchester and the Christie NHS Foundation Trust Manchester Academic Health Science Centre, Manchester
Tatyana Feldman
John Theurer Cancer Center, NJ
Joseph Tuscano
UC Davis Cancer Center, Sacramento, CA
Kerry J. Savage
BC Cancer Centre for Lymphoid Cancer and Department of Medical Oncology, Vancouver
Yasuhiro Oki
Genentech, South San Francisco, CA
Andrew Grigg
Olivia Newton-John Cancer Wellness and Research Centre, Austin Health and Department of Clinical Haemotology, Austin Hospital, Heidelberg
Christopher Pocock
Haematology, East Kent Hospitals, Canterbury
Monika Dlugosz-Danecka
Maria Sklodowska-Curie National Research Institute of Oncology, Krakow
Keenan Fenton
Seagen Inc., Bothell, WA
Andres Forero-Torres
Seagen Inc., Bothell, WA
Rachael Liu
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
Hina Jolin
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
Ashish Gautam
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
Andrea Gallamini
Research and Innovation Department, A Lacassagne Cancer Centre, Nice
Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs. <60 years) was a pre-specified subgroup analysis; as the ECHELON- 1 study was not powered for these analyses, reported P-values are descriptive. Of 1,334 enrolled patients, 186 (14%) were aged ≥60 years (A+AVD: n=84, ABVD: n=102); results below refer to this age group. Modified progression-free survival per independent review facility was similar in the two arms at 24 months (A+AVD: 70.3% [95% confidence interval (CI): 58.4–79.4], ABVD: 71.4% [95% CI: 60.5–79.8], hazard ratio (HR)=1.00 [95% CI: 0.58–1.72], P=0.993). After a median follow-up of 60.9 months, 5-year progression-free survival per investigator was 67.1% with A+AVD versus 61.6% with ABVD (HR=0.820 [95% CI: 0.494–1.362], P=0.443). Comparing A+AVD versus ABVD, grade 3/4 peripheral neuropathy occurred in 18% versus 3%; any-grade febrile neutropenia in 37% versus 17%; and any-grade pulmonary toxicity in 2% versus 13%, respectively, with three (3%) pulmonary toxicity-related deaths in patients receiving ABVD (none in those receiving A+AVD). Altogether, A+AVD showed overall similar efficacy to ABVD with survival rates in both arms comparing favorably to those of prior series in older patients with advanced-stage classical Hodgkin lymphoma. Compared to ABVD, A+AVD was associated with higher rates of neuropathy and neutropenia, but lower rates of pulmonary-related toxicity. Trials registered at ClinicalTrials.gov identifiers: NCT01712490; EudraCT number: 2011-005450-60.
