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J Transl Med. 2018 May 29;16(1):142. doi: 10.1186/s12967-018-1507-6.

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

Author information

1
University of California Los Angeles (UCLA) David Geffen School of Medicine & Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. lliau@mednet.ucla.edu.
2
King's College London School of Medical Education, London, UK.
3
University of Florida, Gainesville, FL, USA.
4
Washington University, St. Louis, MO, USA.
5
Abbott Northwestern Hospital, Minneapolis, MN, USA.
6
Swedish Medical Center, Swedish Neuroscience Institute, Seattle, WA, USA.
7
University of Michigan Medical School, Ann Arbor, MI, USA.
8
University of Kansas Cancer Center, Kansas City, KS, USA.
9
Sutter Institute for Medical Research, Sacramento, CA, USA.
10
Columbia University Medical Center, New York, NY, USA.
11
Indiana University Simon Cancer Center, Indianapolis, IN, USA.
12
Overlook Medical Center, Summit, NJ, USA.
13
University of Rochester Medical Center, Rochester, NY, USA.
14
Rush University Medical Center, Rochester, USA.
15
Rutgers Cancer Institute, New Brunswick, NJ, USA.
16
University of Cincinnati Medical Center, Cincinnati, OH, USA.
17
Hackensack University Medical Center, Hackensack, NJ, USA.
18
UC Irvine Medical Center, Irvine, CA, USA.
19
Winthrop-University Hospital, Mineola, NY, USA.
20
NYU Winthrop Hospital, Mineola, NY, USA.
21
Rhode Island Hospital, Providence, RI, USA.
22
University of Colorado Hospital, Aurora, CO, USA.
23
Henry Ford Health System, Detroit, MI, USA.
24
St. Thomas Research Institute, Nashville, TN, USA.
25
University of Texas Health Science Center, San Antonio, TX, USA.
26
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
27
University of North Carolina, Chapel Hill, NC, USA.
28
City of Hope National Medical Center, Duarte, CA, USA.
29
Thomas Jefferson University, Philadelphia, PA, USA.
30
St. Joseph Hospital, Newport Beach, CA, USA.
31
Vanderbilt University, Nashville, TN, USA.
32
Beth Israel Deaconess Medical Center, Boston, MA, USA.
33
Baylor University Medical Center, Dallas, TX, USA.
34
Illinois CancerCare, Peoria, IL, USA.
35
Medical University of South Carolina, Charleston, SC, USA.
36
Mount Sinai Comprehensive Cancer Center, Miami, FL, USA.
37
University Hospitals Case Medical Center, Cleveland, OH, USA.
38
University Hospital Carl-Gustav-Carus of Technical University, Dresden, Germany.
39
BG-Klinikum Bergmannstrost, Halle, Germany.
40
Tufts University School of Medicine, Boston, MA, USA.
41
Stony Brook University, Stony Brook, NY, USA.
42
Hoag Cancer Center, Newport Beach, CA, USA.
43
H. Lee Moffit Cancer Center and Research Institute, Tampa, FL, USA.
44
CHUS-Hopital Fleurimont, Sherbrooke University, Sherbrooke, QC, Canada.
45
UCSD Health System, UC San Diego, San Diego, CA, USA.
46
Neurochirurgische Klinik University Clinic Hamburg-Eppendorf, Hamburg, Germany.
47
Houston Methodist, Houston, TX, USA.
48
Geisinger Health System, Danville, PA, USA.
49
Klinikum Chemnitz GGMBH, Chemnitz, Germany.
50
Saint Luke's Cancer Institute, Kansas City, MO, USA.
51
Kaiser Permanente Northern California, Redwood City, CA, USA.
52
Kaiser Permanente Southern California, Los Angeles, CA, USA.
53
University of Kentucky College of Medicine, Lexington, KY, USA.
54
Colorado Neurological Institute, Englewood, CO, USA.
55
Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
56
Northwell Hofstra School of Medicine, Lake Success, NY, USA.
57
Department of Neurology, Alvord Brain Tumor Center, University of Washington, Seattle, WA, USA.
58
Northwest Biotherapeutics Inc., Bethesda, MD, USA.
59
University of California Los Angeles (UCLA) David Geffen School of Medicine & Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
60
University College Hospitals, London, UK.
61
Northwest Biotherapeutics Inc., Bethesda, MD, USA. marnix@nwbio.com.

Abstract

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®-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.

KEYWORDS:

Dendritic cell; Glioblastoma; Immunotherapy; Vaccine

PMID:
29843811
PMCID:
PMC5975654
DOI:
10.1186/s12967-018-1507-6
[Indexed for MEDLINE]
Free PMC Article

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