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!