Immunotherapy Options for Primary Central Nervous System Tumors

tibbionko-17-1-kapak

Serhat SEKMEKa , Didem ŞENER DEDEb
aAnkara Bilkent City Hospital, Clinic of Medical Oncology, Ankara, Türkiye
bAnkara Yıldırım Beyazıt University Faculty of Medicine, Ankara Bilkent City Hospital, Department of Medical Oncology, Ankara, Türkiye

Sekmek S, Şener Dede D. Immunotherapy options for primary central nervous system tumors. In: Şendur MAN, ed. Current Immunotherapy Landscape for Solid Tumors. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.18-23.

ABSTRACT
Primary brain tumors (PBTs) occur at a frequency of 2% among all cancers. The most common and most lethal primary brain tumor in adulthood is glioblastoma (GB). In the treatment of PBTs and especially GB, surgery following concomitant radiotherapy given together with temozolomide (TMZ) and maintenance TMZ is still the gold standard. Immunotherapy options such as immune checkpoint inhibitors, oncolytic viruses, vaccines, and CAR-T cell therapies have been tried in this field, and despite partial positive results, they have not yet reached the level that changes clinical practice. However, many ongoing studies will show the place of immunotherapies in the treatment of primary brain tumors.

Keywords: Central nervous system tumor; immunotherapy

Referanslar

  1. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol. 2019;21(Suppl 5):v1-v100. [Crossref]  [PubMed]  [PMC]
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. [Crossref]  [PubMed]
  3. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al.; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-96. [Crossref]  [PubMed]
  4. Fecci PE, Heimberger AB, Sampson JH. Immunotherapy for primary brain tumors: no longer a matter of privilege. Clin Cancer Res. 2014;20(22):5620-9. [Crossref]  [PubMed]  [PMC]
  5. Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992;13(12):507-12. [Crossref]  [PubMed]
  6. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337-41. Erratum in: Nature. 2016;533(7602):278. [Crossref]  [PubMed]  [PMC]
  7. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015;212(7):991-9. [Crossref]  [PubMed]  [PMC]
  8. Reardon DA, Gokhale PC, Klein SR, Ligon KL, Rodig SJ, Ramkissoon SH, et al. Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model. Cancer Immunol Res. 2016;4(2):124-35. [Crossref]  [PubMed]
  9. Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013;86(2):343-9. [Crossref]  [PubMed]  [PMC]
  10. Jacobs JF, Idema AJ, Bol KF, Nierkens S, Grauer OM, Wesseling P, et al. Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. Neuro Oncol. 2009;11(4):394-402. [Crossref]  [PubMed]  [PMC]
  11. Blumenthal DT, Yalon M, Vainer GW, Lossos A, Yust S, Tzach L, et al. Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors. J Neurooncol. 2016;129(3):453-460. [Crossref]  [PubMed]
  12. Roth P, Valavanis A, Weller M. Long-term control and partial remission after initial pseudoprogression of glioblastoma by anti-PD-1 treatment with nivolumab. Neuro Oncol. 2017;19(3):454-6. [Crossref]  [PubMed]  [PMC]
  13. Reardon DA, Kim TM, Frenel JS, Simonelli M, Lopez J, Subramaniam DS, et al. Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Cancer. 2021;127(10):1620-9. [Crossref]  [PubMed]
  14. Nayak L, Molinaro AM, Peters K, Clarke JL, Jordan JT, de Groot J, et al. Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res. 2021;27(4):1048-57. [Crossref]  [PubMed]  [PMC]
  15. Chamberlain MC, Kim BT. Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: a retrospective case series. J Neurooncol. 2017;133(3):561-9. [Crossref]  [PubMed]
  16. Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro Oncol. 2018;20(5):674-86. [Crossref]  [PubMed]  [PMC]
  17. Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, et al. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(7):1003-10. [Crossref]  [PubMed]  [PMC]
  18. Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, et al. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 2022;24(11):1935-49. [Crossref]  [PubMed]  [PMC]
  19. Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, et al. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 2023;25(1):123-34. [Crossref]  [PubMed]  [PMC]
  20. Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019;25(3):477-86. [Crossref]  [PubMed]  [PMC]
  21. Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, López-Janeiro A, Porciuncula A, Idoate MA, et al. Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat Med. 2019;25(3):470-6. [Crossref]  [PubMed]
  22. Sahebjam S, Forsyth PA, Tran ND, Arrington JA, Macaulay R, Etame AB, et al. Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study. Neuro Oncol. 2021;23(4):677-86. [Crossref]  [PubMed]  [PMC]
  23. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015;372(26):2509-20. [Crossref]  [PubMed]  [PMC]
  24. Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, et al. Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. J Clin Oncol. 2016;34(19):2206-11. [Crossref]  [PubMed]
  25. Touat M, Li YY, Boynton AN, Spurr LF, Iorgulescu JB, Bohrson CL, et al. Mechanisms and therapeutic implications of hypermutation in gliomas. Nature. 2020;580(7804):517-23. [Crossref]  [PubMed]  [PMC]
  26. Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, et al. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat Med. 2019;25(3):462-9. Erratum in: Nat Med. 2019. [Crossref]  [PubMed]  [PMC]
  27. Rong L, Li N, Zhang Z. Emerging therapies for glioblastoma: current state and future directions. J Exp Clin Cancer Res. 2022;41(1):142. [Crossref]  [PubMed]  [PMC]
  28. Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, et al. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016;375(26):2561-9. [Crossref]  [PubMed]  [PMC]
  29. Albinger N, Hartmann J, Ullrich E. Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Gene Ther. 2021;28(9):513-27. [Crossref]  [PubMed]  [PMC]
  30. Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science. 1991;252(5007):854-6. [Crossref]  [PubMed]
  31. Westphal M, Ylä-Herttuala S, Martin J, Warnke P, Menei P, Eckland D, et al.; ASPECT Study Group. Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(9):823-33. [Crossref]  [PubMed]
  32. Twumasi-Boateng K, Pettigrew JL, Kwok YYE, Bell JC, Nelson BH. Oncolytic viruses as engineering platforms for combination immunotherapy. Nat Rev Cancer. 2018;18(7):419-32. Erratum in: Nat Rev Cancer. 2018. [Crossref]  [PubMed]
  33. Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al.; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):1373-85. [Crossref]  [PubMed]
  34. Migliorini D, Dutoit V, Allard M, Grandjean Hallez N, Marinari E, Widmer V, et al. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Neuro Oncol. 2019;21(7):923-33. [Crossref]  [PubMed]  [PMC]
  35. Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565(7738):234-9. [Crossref]  [PubMed]  [PMC]
  36. Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanović S, Gouttefangeas C, et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 2019;565(7738):240-5. Erratum in: Nature. 2019;566(7745):E13. [Crossref]  [PubMed]
  37. Liau LM, Ashkan K, Tran DD, Campian JL, Trusheim JE, Cobbs CS, et al. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018;16(1):142. Erratum in: J Transl Med. 2018;16(1):179. [Crossref]  [PubMed]  [PMC]
  38. Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, Yong WH, et al. Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res. 2011;17(6):1603-15. [Crossref]  [PubMed]  [PMC]