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Poster Display session 1

1469 - Pembrolizumab (Pem) in recurrent high-grade glioma (HGG) patients with mismatch repair deficiency (MMRd): an observational study

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Tumour Site

Central Nervous System Malignancies

Presenters

Mario Caccese

Citation

Annals of Oncology (2019) 30 (suppl_5): v143-v158. 10.1093/annonc/mdz243

Authors

M. Caccese1, M. Simonelli2, M. Fassan3, M. Padovan1, P. Persico2, L. Bellu4, A. Dipasquale2, M.P. Gardiman3, S. Indraccolo5, V. Zagonel1, G. Lombardi1

Author affiliations

  • 1 Oncology 1, Department of Oncology, Veneto Institute of Oncology, IOV – IRCCS, 35128 - Padova/IT
  • 2 Department Of Biomedical Sciences, Humanitas University, Humanitas Clinical and Research Hospital - IRCCS, 20089 - Milan/IT
  • 3 Department Of Medicine And Surgical Pathology And Cytopathology Unit, University Hospital of Padua, 35128 - Padua/IT
  • 4 Radioteraphy Unit, Department of Oncology, Veneto Institute of Oncology, IOV – IRCCS, 35128 - Padova/IT
  • 5 Immunology And Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, 35128 - Padua/IT

Resources

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Abstract 1469

Background

Pem, an immune checkpoint inhibitor, has been demonstrated to be active in various neoplasms with MMRd. No data exist about its efficacy in MMRd glioma patients.

Methods

MMRd HGG patients relapsed after receiving RT and CT were treated with Pem. MMR status was analyzed by immunohistochemistry, including the MLH1, MSH2, MSH6, and PMS2 markers. MMR deficiency was defined as presence of a weak (wMMRd) or absent (aMMRd) signal on immunohistochemistry for at least one MMR protein. Other inclusion criteria were: ECOG PS 0-2, histologically confirmed gliomas, dexamethasone ≤4 mg. Pem was administered at 200 mg every 3 weeks until disease progression or unacceptable toxicity. Tumor response was evaluated by brain MRI every 10 weeks according to the RANO criteria. OS and PFS were evaluated by Kaplan-Meier curves. CTCAE v4.0 was used for toxicity assessment.

Results

Among 167 glioma patients, we found 22 MMRd gliomas. 12 PTS were treated with Pem: 8 wMMRd and 4 aMMRd. According to Bethesda criteria, all PTS had microsatellite stability. Tumor histologies included 5 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, 6 glioblastoma (GBM). MSH2 deficiency was found in 6 cases, MSH6 deficiency in 9 cases, PMS2 and MLH1 deficiency in 2 cases. Median number of prior lines of chemotherapy was 1 (range 1-5). Stable disease (SD) was reported in 4 PTS (33%); 8 PTS showed progressive disease (PD). PTS with anaplastic gliomas showed a statistically significant association with SD (p = 0.03, OR = 3); all GBM PTS reported PD; status of MMRd (weak/absent), IDH (mutated/wild-type), MSH2 and MLH6 (deficient/proficient) were not associated with SD. Median follow up was 14.7 ms. OS was 5.6 ms (95% CI 0.1-13.8), PFS 2.4 ms (95% CI 1.8-2.9). OS was 2.8 ms and 5.6 ms (p = 0.9), PFS was 1.8 ms and 3.1 ms (p = 0.5) in PTS with wMMRd and aMMRd. PTS reporting SD and PD had PFS of 7.4 ms (95% CI 4.6-10.2) and 1.8 ms (95% CI 0.2-3.4), p = 0.002; OS was “not reached” and 2.8 ms in PTS having SD vs PD (p = 0.04). Grade ≥3 adverse events were reported in 8% of PTS.

Conclusions

A subgroup of recurrent MMRd HGG patients might benefit from Pem, especially those with anaplastic gliomas. There was a trend for a longer PFS and OS in PTS with aMMRd. Analyses for identifying additional molecular predictive factors is ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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