Present developments with ICPIs:Glioblastoma
Matthias Preusser, MD
Department of Medicine I
Comprehensive Cancer Center Vienna
Medical University of Vienna
Glioblastoma
Axial postcontrast T1-weighted MRI Axial T2-weighted MRI
Abbreviations: AED anti-epileptic drugs, PcP pneuomocystis jirovicii pneumonia, TMZ, temozolomide, RT radiotherapy,
LMWH low molecular weight heparin
† if indicated
PcP prophylaxis: inhaled pentamidine or oral trimethoprim–sulfamethoxazole
Redrawn from: Preusser M et al. Ann Neurol 2011;70(1):9–21
Max.6 weeks
LMWH
Max
. saf
e tu
mo
ur
rese
ctio
n o
r b
iop
sy
AED†
Steroids†
1 6 11 15 19 23 Week
4weeks
4weeksTMZ daily x 40-49 d
PcP prophylaxis
5d 5d 5d x6 cycles
RT 30 x 2 Gy
Therapy of glioblastoma
IO with potential benefit in glioblastoma
• Checkpoint modulators
• Antibody-drug conjugates
• Vaccines
• CAR-T-Cells
Preusser et al. ESMO Open 2017
Preusser et al. ESMO Open 2017
Preusser et al. ESMO Open 2017
Preusser et al. ESMO Open 2017
Blood-brain-barrier
Preusser et al. ESMO Open 2017
Preusser et al. ESMO Open 2017
Blood-brain-barrier
Preusser et al. ESMO Open 2017
Preusser et al. ESMO Open 2017
Tumor-infiltrating lymphocytes in brain tumors
Gehirnmetastase Lungenkarzinom
Glioblastom
Berghoff A (...) Preusser M. Onco-Immunol 2016
Immunoscore in brain metastases
Berghoff A (...) Preusser M. Onco-Immunol 2016
Immune-checkpoint molecules in brain tumors
Glioblastoma
Cortex
White matter
PD-L1
Berghoff A (...) Preusser M. Neurooncol 2014Berghoff A (...) Preusser M. Histopathol 2015Berghoff A (...) Preusser M. J Neurooncl 2016Berghoff A (...) Preusser M. Neurooncol 2017
Primary tumor Brain metastasis
GlioblastomaMelanoma brain metastasis
NSCLC
Anecdotal evidence of anti-PD1 activity in glioblastoma
Roth, Neuro-Oncol 2017
Response to nivolumab in two brothers with biallelic mismatchrepair deficiency (bMMRD)
Bouffet, JCO 2016
Mutational load in glioma
Hodges, Neuro-Oncol 2016
Discovery of polymerase epsilon gene (POLE) mutated ultramutated gliomas
Erson-Omay, Neuro-Oncol, 2015
Response to pembrolizumab in hypermutant POLE deficient glioblastoma
Johans, Cancer Discovery 2016
WFNOS, Zurich, May 2017
Checkmate-498 and Checkmate-548 trialsNivolumab in newly diagnosed glioblastoma
Conclusions
• TILs, PD-L1, hypermutation present in (some) gliomas
• Anectodal evidence of succesful PD-1 inhibition in some cases
• Phase III PD-1 inhibitor trial negative in recurrent glioblastoma
• Clinical trials in newly diagnosed glioblastomaongoing
Thank you!
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