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


  • Daniela Ovadia — Agenzia Zoe
  • Oncology Conference reports
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • 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.

Limitations

  • Single centre study; small sample.

Please confirm your acceptance

To gain full access to GPnotebook please confirm:

By submitting here you confirm that you have accepted Terms of Use and Privacy Policy of GPnotebook.

Submit