ESMO 2019 — Germline hypermutator glioblastomas could benefit from immuno-oncology

  • Daniela Ovadia — Agenzia Zoe
  • Oncology Conference reports
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  • Germline hypermutator glioblastomas (HmGB) may have a durable response to immune-oncology (IO).

Why this matters

  • Glioblastoma is a cold tumour, only 11% have detected lymphocytes.
  • Phase 3 trial on recurrent glioblastomas with nivolumab failed to extend survival.

Study design

  • Independent, retrospective analysis of patients between 2012 through 2018 at a single centre (MD Anderson).
  • 312 gliomas analysed with next-generation sequencing were identified.
  • HmGB was defined as tumour mutational burden of 30 or more mutations per megabase, or mutations in mismatch repair (MMR) or DNA-polymerase genes.

Key results

  • IO seems to be ineffective in HmGB with somatic mutations regardless of the onset of diagnosis or phenotype. However, germline HmGB may have durable responses to IO.
  • 30 (9.6%) patients had HmGB. Of those, 9 (30%) received IO.
  • HmGB was found as initial diagnosis in 5 (56%) cases, the rest after temozolomide (TMZ) treatment.
  • Only 1 patient had germline MMR mutation (Lynch Syndrome).
  • 8 HmGB patients received either checkpoint inhibitors (CPI) or cellular therapy (T-cells or NK cells) after TMZ, only 1 patient received CPI at initial diagnosis.
  • In HmGB with somatic mutations, OS from initial diagnosis was 39 months. PFS was 72 days.
  • PFS after TMZ, CPI, and cell therapies was 51, 41, and 175 days, respectively, whereas the PFS in newly diagnosed HmGB was 96 days.
  • Median cumulative dose of pembrolizumab: 720 mg per patient.
  • The patient with germline HmGB is still on pembrolizumab and is the only one with stable disease for more than 16 months.
  • Funding: none.


  • Single centre study; small sample.

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