title: 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.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Seattle Genetics and Takeda Pharmaceuticals International.
authors: Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: moskowic@mskcc.org.
authors: Craig H
authors: CH
authors: Moskowitz
authors: City of Hope National Medical Center, Duarte, CA, USA.
authors: Auayporn
authors: A
authors: Nademanee
authors: Szent Istvan & Szent Laszlo Corporate Hospital Hematology & Stem Cell Dept, Budapest, Hungary.
authors: Tamas
authors: T
authors: Masszi
authors: Baylor University Medical Center, Dallas, TX, USA.
authors: Edward
authors: E
authors: Agura
authors: Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute of Oncology, Gliwice, Poland.
authors: Jerzy
authors: J
authors: Holowiecki
authors: Karmanos Cancer Institute, Detroit, MI, USA.
authors: Muneer H
authors: MH
authors: Abidi
authors: Oregon Health and Science University, Portland, OR, USA.
authors: Andy I
authors: AI
authors: Chen
authors: Loyola University Medical Center, Maywood, IL, USA.
authors: Patrick
authors: P
authors: Stiff
authors: Istituto Nazionale dei Tumori, Milano, Italy.
authors: Alessandro M
authors: AM
authors: Gianni
authors: IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy.
authors: Angelo
authors: A
authors: Carella
authors: Blokhin Cancer Research Center under the Russian Academy of Medical Sciences, Moscow, Russia.
authors: Dzhelil
authors: D
authors: Osmanov
authors: University of Minnesota, Minneapolis, MN, USA.
authors: Veronika
authors: V
authors: Bachanova
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
authors: John
authors: J
authors: Sweetenham
authors: Institut Catala d'Oncologia-Hospital Duran i Reynals, Barcelona, Spain.
authors: Anna
authors: A
authors: Sureda
authors: Takeda Pharmaceuticals International, Cambridge, MA, USA.
authors: Dirk
authors: D
authors: Huebner
authors: Seattle Genetics, Bothell, WA, USA.
authors: Eric L
authors: EL
authors: Sievers
authors: Takeda Pharmaceuticals International, Cambridge, MA, USA.
authors: Andy
authors: A
authors: Chi
authors: Seattle Genetics, Bothell, WA, USA.
authors: Emily K
authors: EK
authors: Larsen
authors: Seattle Genetics, Bothell, WA, USA.
authors: Naomi N
authors: NN
authors: Hunder
authors: Maria Sklodowska-Curie Institute and Oncology Center, Warszawa, Poland.
authors: Jan
authors: J
authors: Walewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000079963:Brentuximab Vedotin; D060830:Consolidation Chemotherapy / Q000379:methods; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018796:Immunoconjugates; D000079963:Brentuximab Vedotin