Phase III randomized trial of autologous cytokine-induced killer cell immunotherapy for newly diagnosed glioblastoma in Korea.
OBJECTIVE
Adoptive cell immunotherapy involves an ex vivo expansion of autologous cytokine-induced killer (CIK) cells before their reinfusion into the host. We evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy-temozolomide (TMZ) for the treatment of newly diagnosed glioblastomas.


METHODS
In this multi-center, open-label, phase 3 study, we randomly assigned patients with newly diagnosed glioblastoma to receive CIK cell immunotherapy combined with standard TMZ chemoradiotherapy (CIK immunotherapy group) or standard TMZ chemoradiotherapy alone (control group). The efficacy endpoints were analyzed in the intention-to-treat set and in the per protocol set.


RESULTS
Between December 2008 and October 2012, a total of 180 patients were randomly assigned to the CIK immunotherapy (n = 91) or control group (n = 89). In the intention-to-treat analysis set, median PFS was 8.1 months (95% confidence interval (CI), 5.8 to 8.5 months) in the CIK immunotherapy group, as compared to 5.4 months (95% CI, 3.3 to 7.9 months) in the control group (one-sided log-rank, p = 0.0401). Overall survival did not differ significantly between two groups. Grade 3 or higher adverse events, health-related quality of life and performance status between two groups did not show a significant difference.


CONCLUSIONS
The addition of CIK cells immunotherapy to standard chemoradiotherapy with TMZ improved PFS. However, the CIK immunotherapy group did not show evidence of a beneficial effect on overall survival.
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Doo-Sik
DS
Kong
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Do-Hyun
DH
Nam
Department of Neurosurgery, College of Medicine, Korea University, Seoul, Korea.
Shin-Hyuk
SH
Kang
Department of Statistics, Korea University, Seoul, Korea.
Jae Won
JW
Lee
Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea.
Jong-Hee
JH
Chang
Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jeong-Hoon
JH
Kim
Department of Neurosurgery, Kyunghee University Hospital, Seoul, Korea.
Young-Jin
YJ
Lim
Department of Neurosurgery, Konkuk University Medical Center, Seoul, Korea.
Young-Cho
YC
Koh
Department of Neurosurgery, College of Medicine, Korea University, Seoul, Korea.
Yong-Gu
YG
Chung
Department of Neurosurgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
Jae-Min
JM
Kim
Department of Neurosurgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
Choong-Hyun
CH
Kim
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000637:transplantation*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D000077204:Temozolomide; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
autologous cytokine-induced killer cell; glioblastoma; immunotherapy
N Engl J Med. 2014 Feb 20;370(8):699-708
24552317
Expert Opin Biol Ther. 2015 Apr;15(4):481-93
25435128
Lancet Oncol. 2014 Sep;15(10 ):1100-8
25163906
Expert Opin Biol Ther. 2012 Jun;12(6):673-84
22500889
Gastroenterology. 2015 Jun;148(7):1383-91.e6
25747273
Clin Dev Immunol. 2012;2012:473245
23193418
Neurochem Int. 2006 Jul;49(2):195-203
16730862
Exp Hematol Oncol. 2012 Apr 26;1(1):11
23210562
J Clin Oncol. 2013 Nov 10;31(32):4085-91
24101040
J Clin Oncol. 1990 Jul;8(7):1277-80
2358840
N Engl J Med. 2014 Feb 20;370(8):709-22
24552318
Lancet. 2000 Sep 2;356(9232):802-7
11022927
Immunotherapy. 2014;6(6):787-95
25186607
J Clin Oncol. 2010 Apr 10;28(11):1963-72
20231676
Int J Hematol. 2014 Aug;100(2):165-70
24929848
J Cancer Res Clin Oncol. 2011 Feb;137(2):305-10
20407789
Cytotherapy. 2012 Apr;14(4):483-93
22277010
PLoS One. 2014 Nov 20;9(11):e112662
25412106
Br J Cancer. 1999 Nov;81(6):1009-16
10576658
Anticancer Res. 2008 Nov-Dec;28(6B):3997-4002
19192663
Curr Neurol Neurosci Rep. 2005 May;5(3):198-206
15865885
Oncol Rep. 2011 Jan;25(1):33-9
21109954