PMID- 29843811
OWN - NLM
STAT- MEDLINE
DCOM- 20190614
LR  - 20220409
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 16
IP  - 1
DP  - 2018 May 29
TI  - First results on survival from a large Phase 3 clinical trial of an autologous 
      dendritic cell vaccine in newly diagnosed glioblastoma.
PG  - 142
LID - 10.1186/s12967-018-1507-6 [doi]
LID - 142
AB  - BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and 
      temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor 
      lysate-pulsed dendritic cell vaccine (DCVax((R))-L) to standard therapy for newly 
      diagnosed glioblastoma. METHODS: After surgery and chemoradiotherapy, patients 
      were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or 
      temozolomide and placebo (n = 99). Following recurrence, all patients were 
      allowed to receive DCVax-L, without unblinding. The primary endpoint was 
      progression free survival (PFS); the secondary endpoint was overall survival 
      (OS). RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS 
      (mOS) was 23.1 months from surgery. Because of the cross-over trial design, 
      nearly 90% of the ITT population received DCVax-L. For patients with methylated 
      MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 
      46.4%. As of this analysis, 223 patients are >/= 30 months past their surgery date; 
      67 of these (30.0%) have lived >/= 30 months and have a Kaplan-Meier 
      (KM)-derived mOS of 46.5 months. 182 patients are >/= 36 months past surgery; 44 of 
      these (24.2%) have lived >/= 36 months and have a KM-derived mOS of 88.2 months. A 
      population of extended survivors (n = 100) with mOS of 40.5 months, not explained 
      by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients 
      (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly 
      related to the vaccine. Overall adverse events with DCVax were comparable to 
      standard therapy alone. CONCLUSIONS: Addition of DCVax-L to standard therapy is 
      feasible and safe in glioblastoma patients, and may extend survival. Trial 
      registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: 
      NCT00045968; 
      https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; 
      initially registered 19 September 2002.
FAU - Liau, Linda M
AU  - Liau LM
AD  - University of California Los Angeles (UCLA) David Geffen School of Medicine & 
      Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. lliau@mednet.ucla.edu.
FAU - Ashkan, Keyoumars
AU  - Ashkan K
AD  - King's College London School of Medical Education, London, UK.
FAU - Tran, David D
AU  - Tran DD
AD  - University of Florida, Gainesville, FL, USA.
FAU - Campian, Jian L
AU  - Campian JL
AD  - Washington University, St. Louis, MO, USA.
FAU - Trusheim, John E
AU  - Trusheim JE
AD  - Abbott Northwestern Hospital, Minneapolis, MN, USA.
FAU - Cobbs, Charles S
AU  - Cobbs CS
AD  - Swedish Medical Center, Swedish Neuroscience Institute, Seattle, WA, USA.
FAU - Heth, Jason A
AU  - Heth JA
AD  - University of Michigan Medical School, Ann Arbor, MI, USA.
FAU - Salacz, Michael
AU  - Salacz M
AD  - University of Kansas Cancer Center, Kansas City, KS, USA.
FAU - Taylor, Sarah
AU  - Taylor S
AD  - University of Kansas Cancer Center, Kansas City, KS, USA.
FAU - D'Andre, Stacy D
AU  - D'Andre SD
AD  - Sutter Institute for Medical Research, Sacramento, CA, USA.
FAU - Iwamoto, Fabio M
AU  - Iwamoto FM
AD  - Columbia University Medical Center, New York, NY, USA.
FAU - Dropcho, Edward J
AU  - Dropcho EJ
AD  - Indiana University Simon Cancer Center, Indianapolis, IN, USA.
FAU - Moshel, Yaron A
AU  - Moshel YA
AD  - Overlook Medical Center, Summit, NJ, USA.
FAU - Walter, Kevin A
AU  - Walter KA
AD  - University of Rochester Medical Center, Rochester, NY, USA.
FAU - Pillainayagam, Clement P
AU  - Pillainayagam CP
AD  - Rush University Medical Center, Rochester, USA.
FAU - Aiken, Robert
AU  - Aiken R
AD  - Rutgers Cancer Institute, New Brunswick, NJ, USA.
FAU - Chaudhary, Rekha
AU  - Chaudhary R
AD  - University of Cincinnati Medical Center, Cincinnati, OH, USA.
FAU - Goldlust, Samuel A
AU  - Goldlust SA
AD  - Hackensack University Medical Center, Hackensack, NJ, USA.
FAU - Bota, Daniela A
AU  - Bota DA
AD  - UC Irvine Medical Center, Irvine, CA, USA.
FAU - Duic, Paul
AU  - Duic P
AD  - Winthrop-University Hospital, Mineola, NY, USA.
FAU - Grewal, Jai
AU  - Grewal J
AD  - NYU Winthrop Hospital, Mineola, NY, USA.
FAU - Elinzano, Heinrich
AU  - Elinzano H
AD  - Rhode Island Hospital, Providence, RI, USA.
FAU - Toms, Steven A
AU  - Toms SA
AD  - Rhode Island Hospital, Providence, RI, USA.
FAU - Lillehei, Kevin O
AU  - Lillehei KO
AD  - University of Colorado Hospital, Aurora, CO, USA.
FAU - Mikkelsen, Tom
AU  - Mikkelsen T
AD  - Henry Ford Health System, Detroit, MI, USA.
FAU - Walbert, Tobias
AU  - Walbert T
AD  - Henry Ford Health System, Detroit, MI, USA.
FAU - Abram, Steven R
AU  - Abram SR
AD  - St. Thomas Research Institute, Nashville, TN, USA.
FAU - Brenner, Andrew J
AU  - Brenner AJ
AD  - University of Texas Health Science Center, San Antonio, TX, USA.
FAU - Brem, Steven
AU  - Brem S
AD  - University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
FAU - Ewend, Matthew G
AU  - Ewend MG
AD  - University of North Carolina, Chapel Hill, NC, USA.
FAU - Khagi, Simon
AU  - Khagi S
AD  - University of North Carolina, Chapel Hill, NC, USA.
FAU - Portnow, Jana
AU  - Portnow J
AD  - City of Hope National Medical Center, Duarte, CA, USA.
FAU - Kim, Lyndon J
AU  - Kim LJ
AD  - Thomas Jefferson University, Philadelphia, PA, USA.
FAU - Loudon, William G
AU  - Loudon WG
AD  - St. Joseph Hospital, Newport Beach, CA, USA.
FAU - Thompson, Reid C
AU  - Thompson RC
AD  - Vanderbilt University, Nashville, TN, USA.
FAU - Avigan, David E
AU  - Avigan DE
AD  - Beth Israel Deaconess Medical Center, Boston, MA, USA.
FAU - Fink, Karen L
AU  - Fink KL
AD  - Baylor University Medical Center, Dallas, TX, USA.
FAU - Geoffroy, Francois J
AU  - Geoffroy FJ
AD  - Illinois CancerCare, Peoria, IL, USA.
FAU - Lindhorst, Scott
AU  - Lindhorst S
AD  - Medical University of South Carolina, Charleston, SC, USA.
FAU - Lutzky, Jose
AU  - Lutzky J
AD  - Mount Sinai Comprehensive Cancer Center, Miami, FL, USA.
FAU - Sloan, Andrew E
AU  - Sloan AE
AD  - University Hospitals Case Medical Center, Cleveland, OH, USA.
FAU - Schackert, Gabriele
AU  - Schackert G
AD  - University Hospital Carl-Gustav-Carus of Technical University, Dresden, Germany.
FAU - Krex, Dietmar
AU  - Krex D
AD  - University Hospital Carl-Gustav-Carus of Technical University, Dresden, Germany.
FAU - Meisel, Hans-Jorg
AU  - Meisel HJ
AD  - BG-Klinikum Bergmannstrost, Halle, Germany.
FAU - Wu, Julian
AU  - Wu J
AD  - Tufts University School of Medicine, Boston, MA, USA.
FAU - Davis, Raphael P
AU  - Davis RP
AD  - Stony Brook University, Stony Brook, NY, USA.
FAU - Duma, Christopher
AU  - Duma C
AD  - Hoag Cancer Center, Newport Beach, CA, USA.
FAU - Etame, Arnold B
AU  - Etame AB
AD  - H. Lee Moffit Cancer Center and Research Institute, Tampa, FL, USA.
FAU - Mathieu, David
AU  - Mathieu D
AD  - CHUS-Hopital Fleurimont, Sherbrooke University, Sherbrooke, QC, Canada.
FAU - Kesari, Santosh
AU  - Kesari S
AD  - UCSD Health System, UC San Diego, San Diego, CA, USA.
FAU - Piccioni, David
AU  - Piccioni D
AD  - UCSD Health System, UC San Diego, San Diego, CA, USA.
FAU - Westphal, Manfred
AU  - Westphal M
AD  - Neurochirurgische Klinik University Clinic Hamburg-Eppendorf, Hamburg, Germany.
FAU - Baskin, David S
AU  - Baskin DS
AD  - Houston Methodist, Houston, TX, USA.
FAU - New, Pamela Z
AU  - New PZ
AD  - Houston Methodist, Houston, TX, USA.
FAU - Lacroix, Michel
AU  - Lacroix M
AD  - Geisinger Health System, Danville, PA, USA.
FAU - May, Sven-Axel
AU  - May SA
AD  - Klinikum Chemnitz GGMBH, Chemnitz, Germany.
FAU - Pluard, Timothy J
AU  - Pluard TJ
AD  - Saint Luke's Cancer Institute, Kansas City, MO, USA.
FAU - Tse, Victor
AU  - Tse V
AD  - Kaiser Permanente Northern California, Redwood City, CA, USA.
FAU - Green, Richard M
AU  - Green RM
AD  - Kaiser Permanente Southern California, Los Angeles, CA, USA.
FAU - Villano, John L
AU  - Villano JL
AD  - University of Kentucky College of Medicine, Lexington, KY, USA.
FAU - Pearlman, Michael
AU  - Pearlman M
AD  - Colorado Neurological Institute, Englewood, CO, USA.
FAU - Petrecca, Kevin
AU  - Petrecca K
AD  - Montreal Neurological Institute and Hospital, McGill University, Montreal, 
      Canada.
FAU - Schulder, Michael
AU  - Schulder M
AD  - Northwell Hofstra School of Medicine, Lake Success, NY, USA.
FAU - Taylor, Lynne P
AU  - Taylor LP
AD  - Department of Neurology, Alvord Brain Tumor Center, University of Washington, 
      Seattle, WA, USA.
FAU - Maida, Anthony E
AU  - Maida AE
AD  - Northwest Biotherapeutics Inc., Bethesda, MD, USA.
FAU - Prins, Robert M
AU  - Prins RM
AD  - University of California Los Angeles (UCLA) David Geffen School of Medicine & 
      Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
FAU - Cloughesy, Timothy F
AU  - Cloughesy TF
AD  - University of California Los Angeles (UCLA) David Geffen School of Medicine & 
      Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
FAU - Mulholland, Paul
AU  - Mulholland P
AD  - University College Hospitals, London, UK.
FAU - Bosch, Marnix L
AU  - Bosch ML
AUID- ORCID: 0000-0002-8831-8456
AD  - Northwest Biotherapeutics Inc., Bethesda, MD, USA. marnix@nwbio.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT00045968
GR  - P50 CA211015/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180529
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Cancer Vaccines)
SB  - IM
EIN - J Transl Med. 2018 Jun 29;16(1):179. PMID: 29958537
MH  - Adult
MH  - Aged
MH  - Brain Neoplasms/diagnosis/*immunology/*therapy
MH  - Cancer Vaccines/adverse effects/*immunology
MH  - Dendritic Cells/*immunology
MH  - Endpoint Determination
MH  - Female
MH  - Glioblastoma/diagnosis/*immunology/*therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC5975654
OTO - NOTNLM
OT  - Dendritic cell
OT  - Glioblastoma
OT  - Immunotherapy
OT  - Vaccine
EDAT- 2018/05/31 06:00
MHDA- 2019/06/15 06:00
PMCR- 2018/05/29
CRDT- 2018/05/31 06:00
PHST- 2018/04/27 00:00 [received]
PHST- 2018/05/07 00:00 [accepted]
PHST- 2018/05/31 06:00 [entrez]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2019/06/15 06:00 [medline]
PHST- 2018/05/29 00:00 [pmc-release]
AID - 10.1186/s12967-018-1507-6 [pii]
AID - 1507 [pii]
AID - 10.1186/s12967-018-1507-6 [doi]
PST - epublish
SO  - J Transl Med. 2018 May 29;16(1):142. doi: 10.1186/s12967-018-1507-6.