Startseite Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis
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Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis

  • Sara Hanaei , Khashayar Afshari , Armin Hirbod-Mobarakeh , Bahram Mohajer , Delara Amir Dastmalchi und Nima Rezaei EMAIL logo
Veröffentlicht/Copyright: 10. Januar 2018
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Reviews in the Neurosciences
Aus der Zeitschrift Reviews in the Neurosciences Band 29 Heft 4

Abstract

Although different immunotherapeutic approaches have been developed for the treatment of glioma, there is a discrepancy between clinical trials limiting their approval as common treatment. So, the current systematic review and meta-analysis were conducted to assess survival and clinical response of specific immunotherapy in patients with glioma. Generally, seven databases were searched to find eligible studies. Controlled clinical trials investigating the efficacy of specific immunotherapy in glioma were found eligible. After data extraction and risk of bias assessment, the data were analyzed based on the level of heterogeneity. Overall, 25 articles with 2964 patients were included. Generally, mean overall survival did not statistically improve in immunotherapy [median difference=1.51; 95% confidence interval (CI)=−0.16–3.17; p=0.08]; however, it was 11.16 months higher in passive immunotherapy (95% CI=5.69–16.64; p<0.0001). One-year overall survival was significantly higher in immunotherapy groups [hazard ratio (HR)=0.69; 95% CI=0.52–0.92; p=0.01]. As the hazard rate in the immunotherapy approach was 0.83 of the control group, 2-year overall survival was significantly higher in immunotherapy (HR=0.83; 95% CI=0.69–0.99; p=0.04). Three-year overall survival was significantly higher in immunotherapy as well (HR=0.67; 95% CI=0.48–0.92; p=0.01). Overall, median progression-free survival was significantly higher in immunotherapy (standard median difference=0.323; 95% CI=0.110–0.536; p=0.003). However, 1-year progression-free survival was not remarkably different between immunotherapy and control groups (HR=0.94; 95% CI=0.74–1.18; p=0.59). Specific immunotherapy demonstrated remarkable improvement in survival of patients with glioma and could be a considerable choice of treatment in the future. Despite the current promising results, further high-quality randomized controlled trials are required to approve immunotherapeutic approaches as the standard of care and the front-line treatment for glioma.

Keywords: active immunotherapy; brain neoplasms; glial cell tumor; glioma; passive immunotherapy

Acknowledgments

The whole design of the systematic review was based on the BITERN and Cochrane protocol for conducting systematic reviews and meta-analysis. The manuscript structure and analyses were all applied according to the Cochrane protocol and Review Manager (RevMan) (Version 5.3. The Nordic Cochrane Centre, Copenhagen, Denmark). This study was not funded by any organization or institution.

  1. Conflict of interest statement: The authors have no conflicts of interest to declare. The authors alone are responsible for the content and writing of the paper.

References

Bloom, H., Peckham, M., Richardson, A., Alexander, P., and Payne, P. (1973). Glioblastoma multiforme: a controlled trial to assess the value of specific active immunotherapy in patients treated by radical surgery and radiotherapy. Br. J. Cancer 27, 253–267.10.1038/bjc.1973.30Suche in Google Scholar PubMed PubMed Central

Calinescu, A.-A., Kamran, N., Baker, G., Mineharu, Y., Lowenstein, P.R., and Castro, M.G. (2015). Overview of current immunotherapeutic strategies for glioma. Immunotherapy 7, 1073–1104.10.2217/imt.15.75Suche in Google Scholar PubMed PubMed Central

Chang, C.-N., Huang, Y.-C., Yang, D.-M., Kikuta, K., Wei, K.-J., Kubota, T., and Yang, W.-K. (2011). A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma. J. Clin. Neurosci. 18, 1048–1054.10.1016/j.jocn.2010.11.034Suche in Google Scholar PubMed

Cho, D.-Y., Yang, W.-K., Lee, H.-C., Hsu, D.-M., Lin, H.-L., Lin, S.-Z., Chen, C.-C., Harn, H.-J., Liu, C.-L., and Lee, W.-Y. (2012). Adjuvant immunotherapy with whole-cell lysate dendritic cells vaccine for glioblastoma multiforme: a phase II clinical trial. World Neurosurg. 77, 736–744.10.1016/j.wneu.2011.08.020Suche in Google Scholar PubMed

Cohen-Inbar, O. and Zaaroor, M. (2016). Immunological aspects of malignant gliomas. Can. J. Neurol. Sci. 43, 494–502.10.1017/cjn.2016.34Suche in Google Scholar PubMed

Deeks, J.J., Higgins, J.P., and Altman, D.G. (2008). Analysing Data and Undertaking Meta-Analyses. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series. J. P. Higgins and S. Green, eds. (Chichester, UK: John Wiley and Sons), pp. 243–296.10.1002/9780470712184.ch9Suche in Google Scholar

Delgado-Lopez, P. and Corrales-Garcia, E. (2016). Survival in glioblastoma: a review on the impact of treatment modalities. Clin. Transl. Oncol. 18, 1062–1071.10.1007/s12094-016-1497-xSuche in Google Scholar PubMed

Dillman, R.O., Duma, C.M., Schiltz, P.M., DePriest, C., Ellis, R.A., Okamoto, K., Beutel, L.D., de Leon, C., and Chico, S. (2004). Intracavitary placement of autologous lymphokine-activated killer (LAK) cells after resection of recurrent glioblastoma. J. Immunother. 27, 398–404.10.1097/00002371-200409000-00009Suche in Google Scholar PubMed

Elledge, R.M., Green, S., Howes, L., Clark, G.M., Berardo, M., Allred, D.C., Pugh, R., Ciocca, D., Ravdin, P., and O’Sullivan, J. (1997). bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study. J. Clin. Oncol. 15, 1916–1922.10.1200/JCO.1997.15.5.1916Suche in Google Scholar PubMed

Fong, B., Jin, R., Wang, X., Safaee, M., Lisiero, D.N., Yang, I., Li, G., Liau, L.M., and Prins, R.M. (2012). Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients. PLoS One 7, e32614.10.1371/journal.pone.0032614Suche in Google Scholar PubMed PubMed Central

Gilbert, M.R., Dignam, J.J., Armstrong, T.S., Wefel, J.S., Blumenthal, D.T., Vogelbaum, M.A., Colman, H., Chakravarti, A., Pugh, S., and Won, M. (2014). A randomized trial of bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 370, 699–708.10.1056/NEJMoa1308573Suche in Google Scholar PubMed PubMed Central

Han, S.J., Zygourakis, C., Lim, M., and Parsa, A.T. (2012). Immunotherapy for glioma: promises and challenges. Neurosurg. Clin. N. Am. 23, 357–370.10.1016/j.nec.2012.05.001Suche in Google Scholar PubMed

Hayes, R.L., Koslow, M., Hiesiger, E.M., Hymes, K.B., Moore, E.J., Pierz, D.M., Hochster, H.S., Chen, D.K., Budzilovich, G.N., and Ransohoff, J. (1995). Improved long term survival after intracavitary interleukin-2 and lymphokine-activated killer cells for adults with recurrent malignant glioma. Cancer 76, 840–852.10.1002/1097-0142(19950901)76:5<840::AID-CNCR2820760519>3.0.CO;2-RSuche in Google Scholar

Hayes, R.L., Arbit, E., Odaimi, M., Pannullo, S., Scheff, R., Kravchinskiy, D., and Zaroulis, C. (2001). Adoptive cellular immunotherapy for the treatment of malignant gliomas. Crit. Rev. Oncol. Hematol. 39, 31–42.10.1016/S1040-8428(01)00122-6Suche in Google Scholar

Higgins, J. and Altman, D. (2008). Assessing Risk of Bias in Included Studies. Cochrane Handbook for Systematic Reviews of Interventions, Version 50. J. Higgins and S. Green, eds. (Chichester, UK: John Wiley and Sons, Ltd).10.1002/9780470712184.ch8Suche in Google Scholar

Jie, X., Hua, L., Jiang, W., Feng, F., Feng, G., and Hua, Z. (2012). Clinical application of a dendritic cell vaccine raised against heat-shocked glioblastoma. Cell Biochem. Biophys. 62, 91–99.10.1007/s12013-011-9265-6Suche in Google Scholar

Kamran, N., Calinescu, A., Candolfi, M., Chandran, M., Mineharu, Y., Asad, A.S., Koschmann, C., Nunez, F.J., Lowenstein, P.R., and Castro, M.G. (2016). Recent advances and future of immunotherapy for glioblastoma. Expert Opin. Biol. Ther. 16, 1245–1264.10.1080/14712598.2016.1212012Suche in Google Scholar

Kong, D.-S., Nam, D.-H., Kang, S.-H., Lee, J.W., Chang, J.-H., Kim, J.-H., Lim, Y.-J., Koh, Y.-C., Chung, Y.-G., and Kim, J.-M. (2017). Phase III randomized trial of autologous cytokine-induced killer cell immunotherapy for newly diagnosed glioblastoma in Korea. Oncotarget 8, 7003–7013.10.18632/oncotarget.12273Suche in Google Scholar

Lemke, D.M. (2004). Epidemiology, diagnosis, and treatment of patients with metastatic cancer and high-grade gliomas of the central nervous system. J. Infus. Nurs. 27, 263–269.10.1097/00129804-200407000-00012Suche in Google Scholar

Leplina, O.Y., Stupak, V., Kozlov, Y.P., Pendyurin, I., Nikonov, S., Tikhonova, M., Sycheva, N., Ostanin, A., and Chernykh, E. (2007). Use of interferon-α-induced dendritic cells in the therapy of patients with malignant brain gliomas. Bull. Exp. Biol. Med. 143, 528–534.10.1007/s10517-007-0172-1Suche in Google Scholar

Li, L., Quang, T.S., Gracely, E.J., Kim, J.H., Emrich, J.G., Yaeger, T.E., Jenrette, J.M., Cohen, S.C., Black, P., and Brady, L.W. (2010). A Phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme. J. Neurosurg. 113, 192–198.10.3171/2010.2.JNS091211Suche in Google Scholar PubMed

Liau, L.M., Prins, R.M., Kiertscher, S.M., Odesa, S.K., Kremen, T.J., Giovannone, A.J., Lin, J.-W., Chute, D.J., Mischel, P.S., and Cloughesy, T.F. (2005). Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin. Cancer Res. 11, 5515–5525.10.1158/1078-0432.CCR-05-0464Suche in Google Scholar PubMed

McNeill, K.A. (2016). Epidemiology of brain tumors. Neurol Clin 34, 981–998.10.1016/j.ncl.2016.06.014Suche in Google Scholar PubMed

Nicholas, M.K. (2007). Glioblastoma multiforme: evidence-based approach to therapy. Expert Rev. Anticancer Ther. 7, S23–S27.10.1586/14737140.7.12s.S23Suche in Google Scholar PubMed

Okada, H., Kohanbash, G., Zhu, X., Kastenhuber, E.R., Hoji, A., Ueda, R., and Fujita, M. (2009). Immunotherapeutic approaches for glioma. Crit. Rev. Immunol. 29, 1–42.10.1615/CritRevImmunol.v29.i1.10Suche in Google Scholar PubMed PubMed Central

Ostrom, Q.T., Bauchet, L., Davis, F.G., Deltour, I., Fisher, J.L., Langer, C.E., Pekmezci, M., Schwartzbaum, J.A., Turner, M.C., and Walsh, K.M. (2014). The epidemiology of glioma in adults: a ‘state of the science’ review. Neuro Oncol 16, 896–913.10.1093/neuonc/nou087Suche in Google Scholar PubMed PubMed Central

Ostrom, Q.T., Gittleman, H., Xu, J., Kromer, C., Wolinsky, Y., Kruchko, C., and Barnholtz-Sloan, J.S. (2016). CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro Oncol 18, v1–v75.10.1093/neuonc/now207Suche in Google Scholar PubMed PubMed Central

Parney, I.F. (2012). Basic concepts in glioma immunology. Adv Exp Med Biol 746, 42–52.10.1007/978-1-4614-3146-6_4Suche in Google Scholar PubMed

Reardon, D.A., Herndon, J.E. II, Peters, K., Desjardins, A., Coan, A., Lou, E., Sumrall, A., Turner, S., Sathornsumetee, S., and Rich, J.N. (2012). Outcome after bevacizumab clinical trial therapy among recurrent grade III malignant glioma patients. J. Neurooncol. 107, 213–221.10.1007/s11060-011-0740-0Suche in Google Scholar PubMed PubMed Central

Sampson, J.H., Heimberger, A.B., Archer, G.E., Aldape, K.D., Friedman, A.H., Friedman, H.S., Gilbert, M.R., Herndon, J.E., McLendon, R.E., and Mitchell, D.A. (2010). Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 28, 4722–4729.10.1200/JCO.2010.28.6963Suche in Google Scholar PubMed PubMed Central

Schneider, T., Gerhards, R., Kirches, E., and Firsching, R. (2001). Preliminary results of active specific immunization with modified tumor cell vaccine in glioblastoma multiforme. J. Neurooncol. 53, 39–46.10.1023/A:1011856406683Suche in Google Scholar

Solomón, M.T., Selva, J.C., Figueredo, J., Vaquer, J., Toledo, C., Quintanal, N., Salva, S., Domíngez, R., Alert, J., and Marinello, J.J. (2013). Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial. BMC Cancer 13, 299.10.1186/1471-2407-13-299Suche in Google Scholar PubMed PubMed Central

Vaquero, J., Martinez, R., Ramiro, J., Salazar, F.G., Barbolla, L., and Regidor, C. (1991). Immunotherapy of glioblastoma with intratumoural administration of autologous lymphocytes and human lymphoblastoid interferon. A further clinical study. Acta Neurochir. 109, 42–45.10.1007/BF01405696Suche in Google Scholar PubMed

Vik-Mo, E.O., Nyakas, M., Mikkelsen, B.V., Moe, M.C., Due-Tønnesen, P., Suso, E.M.I., Sæbøe-Larssen, S., Sandberg, C., Brinchmann, J.E., and Helseth, E. (2013). Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol. Immunother. 62, 1499–1509.10.1007/s00262-013-1453-3Suche in Google Scholar PubMed PubMed Central

Weller, M., Butowski, N., Tran, D.D., Recht, L.D., Lim, M., Hirte, H., Ashby, L., Mechtler, L., Goldlust, S.A., and Iwamoto, F. (2017). Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 18, 1373–1385.10.1093/neuonc/now212.068Suche in Google Scholar

Westphal, M., Heese, O., Steinbach, J.P., Schnell, O., Schackert, G., Mehdorn, M., Schulz, D., Simon, M., Schlegel, U., and Senft, C. (2015). A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur. J. Cancer 51, 522–532.10.1016/j.ejca.2014.12.019Suche in Google Scholar PubMed

Wygoda, Z., Kula, D., Bierzynska-Macyszynz, G., Larysz, D., Jarzab, M., Wlaszcz, P., Owski, P.B., Wojtacha, M., Rudnik, A., and Stepien, T. (2006). Use of monoclonal anti-EGFR antibody in the radioimmunotherapy of malignant gliomas in the context of EGFR expression in grade III and IV tumors. Hybridoma 25, 125–132.10.1089/hyb.2006.25.125Suche in Google Scholar PubMed

Yamanaka, R., Yajima, N., Abe, T., Tsuchiya, N., Homma, J., Narita, M., Takahashi, M., and Tanaka, R. (2003). Dendritic cell-based glioma immunotherapy (Review). Int. J. Oncol. 23, 5–15.10.3892/ijo.23.1.5Suche in Google Scholar

Yamanaka, R., Homma, J., Yajima, N., Tsuchiya, N., Sano, M., Kobayashi, T., Yoshida, S., Abe, T., Narita, M., and Takahashi, M. (2005). Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin. Cancer Res. 11, 4160–4167.10.1158/1078-0432.CCR-05-0120Suche in Google Scholar PubMed

Yang, M.-Y., Zetler, P.M., Prins, R.M., Khan-Farooqi, H., and Liau, L.M. (2006). Immunotherapy for patients with malignant glioma: from theoretical principles to clinical applications. Expert Rev. Neurother. 6, 1481–1494.10.1586/14737175.6.10.1481Suche in Google Scholar PubMed

Yu, J.S., Wheeler, C.J., Zeltzer, P.M., Ying, H., Finger, D.N., Lee, P.K., Yong, W.H., Incardona, F., Thompson, R.C., and Riedinger, M.S. (2001). Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res. 61, 842–847.Suche in Google Scholar

Yu, J.S., Liu, G., Ying, H., Yong, W.H., Black, K.L., and Wheeler, C.J. (2004). Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res. 64, 4973–4979.10.1158/0008-5472.CAN-03-3505Suche in Google Scholar PubMed

Supplemental Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/revneuro-2017-0057).

Received: 2017-07-21
Accepted: 2017-10-02
Published Online: 2018-01-10
Published in Print: 2018-06-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Neuroanatomy of conversion disorder: towards a network approach
  3. Calcitonin gene-related peptide (CGRP): role in peripheral nerve regeneration
  4. Role of central oxytocin and dopamine systems in nociception and their possible interactions: suggested hypotheses
  5. Mechanisms of disordered neurodegenerative function: concepts and facts about the different roles of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)
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  7. Cracking novel shared targets between epilepsy and Alzheimer’s disease: need of the hour
  8. Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis
  9. Crossover design in transcranial direct current stimulation studies on motor learning: potential pitfalls and difficulties in interpretation of findings
https://doi.org/10.1515/revneuro-2017-0057
Schlagwörter für diesen Artikel
active immunotherapy; brain neoplasms; glial cell tumor; glioma; passive immunotherapy

Artikel in diesem Heft

  1. Frontmatter
  2. Neuroanatomy of conversion disorder: towards a network approach
  3. Calcitonin gene-related peptide (CGRP): role in peripheral nerve regeneration
  4. Role of central oxytocin and dopamine systems in nociception and their possible interactions: suggested hypotheses
  5. Mechanisms of disordered neurodegenerative function: concepts and facts about the different roles of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)
  6. Mechanisms of action of intravenous immunoglobulin in septic encephalopathy
  7. Cracking novel shared targets between epilepsy and Alzheimer’s disease: need of the hour
  8. Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis
  9. Crossover design in transcranial direct current stimulation studies on motor learning: potential pitfalls and difficulties in interpretation of findings
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