Brentuximab vedotin as consolidation therapy after autologous stem-cell
transplantation in patients with Hodgkin's lymphoma at risk of relapse or
progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3
trial.
Author(s): Moskowitz CH(1), Nademanee A(2), Masszi T(3), Agura E(4), Holowiecki J(5), Abidi
MH(6), Chen AI(7), Stiff P(8), Gianni AM(9), Carella A(10), Osmanov D(11),
Bachanova V(12), Sweetenham J(13), Sureda A(14), Huebner D(15), Sievers EL(16),
Chi A(15), Larsen EK(16), Hunder NN(16), Walewski J(17); AETHERA Study Group.
Affiliation(s): Author information:
(1)Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:
moskowic@mskcc.org. (2)City of Hope National Medical Center, Duarte, CA, USA.
(3)Szent Istvan & Szent Laszlo Corporate Hospital Hematology & Stem Cell Dept,
Budapest, Hungary. (4)Baylor University Medical Center, Dallas, TX, USA.
(5)Department of Bone Marrow Transplantation and Oncohematology, Maria
Sklodowska-Curie Institute of Oncology, Gliwice, Poland. (6)Karmanos Cancer
Institute, Detroit, MI, USA. (7)Oregon Health and Science University, Portland,
OR, USA. (8)Loyola University Medical Center, Maywood, IL, USA. (9)Istituto
Nazionale dei Tumori, Milano, Italy. (10)IRCCS Azienda Ospedaliera Universitaria
San Martino-IST, Genova, Italy. (11)Blokhin Cancer Research Center under the
Russian Academy of Medical Sciences, Moscow, Russia. (12)University of Minnesota,
Minneapolis, MN, USA. (13)Huntsman Cancer Institute, University of Utah, Salt
Lake City, UT, USA. (14)Institut Catala d'Oncologia-Hospital Duran i Reynals,
Barcelona, Spain. (15)Takeda Pharmaceuticals International, Cambridge, MA, USA.
(16)Seattle Genetics, Bothell, WA, USA. (17)Maria Sklodowska-Curie Institute and
Oncology Center, Warszawa, Poland.
Publication date & source: 2015, Lancet. , 385(9980):1853-62
BACKGROUND: High-dose therapy followed by autologous stem-cell transplantation is
standard of care for patients with relapsed or primary refractory Hodgkin's
lymphoma. Roughly 50% of patients might be cured after autologous stem-cell
transplantation; however, most patients with unfavourable risk factors progress
after transplantation. We aimed to assess whether brentuximab vedotin improves
progression-free survival when given as early consolidation after autologous
stem-cell transplantation.
METHODS: We did this randomised, double-blind, placebo-controlled, phase 3 trial
at 78 sites in North America and Europe. Patients with unfavourable-risk relapsed
or primary refractory classic Hodgkin's lymphoma who had undergone autologous
stem-cell transplantation were randomly assigned, by fixed-block randomisation
with a computer-generated random number sequence, to receive 16 cycles of 1·8
mg/kg brentuximab vedotin or placebo intravenously every 3 weeks, starting 30-45
days after transplantation. Randomisation was stratified by best clinical
response after completion of salvage chemotherapy (complete response vs partial
response vs stable disease) and primary refractory Hodgkin's lymphoma versus
relapsed disease less than 12 months after completion of frontline therapy versus
relapse 12 months or more after treatment completion. Patients and study
investigators were masked to treatment assignment. The primary endpoint was
progression-free survival by independent review, defined as the time from
randomisation to the first documentation of tumour progression or death. Analysis
was by intention to treat. This trial is registered with ClinicalTrials.gov,
number NCT01100502.
FINDINGS: Between April 6, 2010, and Sept 21, 2012, we randomly assigned 329
patients to the brentuximab vedotin group (n=165) or the placebo group (n=164).
Progression-free survival by independent review was significantly improved in
patients in the brentuximab vedotin group compared with those in the placebo
group (hazard ratio [HR] 0·57, 95% CI 0·40-0·81; p=0·0013). Median
progression-free survival by independent review was 42·9 months (95% CI
30·4-42·9) for patients in the brentuximab vedotin group compared with 24·1
months (11·5-not estimable) for those in the placebo group. We recorded
consistent benefit (HR <1) of brentuximab vedotin consolidation across subgroups.
The most frequent adverse events in the brentuximab vedotin group were peripheral
sensory neuropathy (94 [56%] of 167 patients vs 25 [16%] of 160 patients in the
placebo group) and neutropenia (58 [35%] vs 19 [12%] patients). At time of
analysis, 28 (17%) of 167 patients had died in the brentuximab vedotin group
compared with 25 (16%) of 160 patients in the placebo group.
INTERPRETATION: Early consolidation with brentuximab vedotin after autologous
stem-cell transplantation improved progression-free survival in patients with
Hodgkin's lymphoma with risk factors for relapse or progression after
transplantation. This treatment provides an important therapeutic option for
patients undergoing autologous stem-cell transplantation.
FUNDING: Seattle Genetics and Takeda Pharmaceuticals International.
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