Extended Data Fig. 10: Extended outcome data.
From: Mechanisms and therapeutic implications of hypermutation in gliomas
a–c, Survival of patients with recurrent high-grade glioma (WHO grade III or IV) from the time of initial diagnosis according to TMB status (solid curves, TMBlow; dotted curves, TMBhigh). The curves include 240 recurrent samples from DFCI-Profile with available survival data from initial diagnosis. Two-sided log-rank test. a, Survival of patients with recurrent high-grade 1p/19q co-deleted oligodendroglioma from the time of initial diagnosis. b, Survival of patients with recurrent high-grade IDH1/2-mutant astrocytoma from the time of initial diagnosis. c, Survival of patients with recurrent IDH1/2 wild-type glioblastoma from the time of initial diagnosis. d, PFS of 11 patients with hypermutated and MMR-deficient glioma who were treated with PD-1 blockade (single-agent or in combination with bevacizumab, red curve). A cohort of patients with non-hypermutated glioma who were treated with PD-1 blockade is depicted as control (n = 10, best matches according to diagnosis, primary versus recurrent status, and prior treatments, blue curve). A two-sided log-rank test is used. e, f, PFS (e) and OS (f) of 11 patients with hypermutated and MMR-deficient glioma who were treated with PD-1 blockade (red curves). A cohort of hypermutated patients treated with other systemic agents is depicted as control (best matches according to diagnosis, primary vs recurrent status, and prior treatments were selected from the cohort of sequenced gliomas, purple curves). Two-sided log-rank test. Clinical and histomolecular characteristics of patients from both cohorts are provided in Supplementary Table 7. g, Lack of immune response following PD1 blockade (pembrolizumab) in a patient with post-treatment hypermutated MMR-deficient glioblastoma. Top, timeline; middle, MRI images; bottom, H&E images and IHC for PMS2 expression and tumour infiltration with CD3-positive T cells and IBA1-positive macrophages in the primary (S1), recurrent pre-pembrolizumab (S3) and recurrent post-pembrolizumab (S4) tumours. The tumour acquired a focal PMS2 two-copy deletion, protein loss, and hypermutation in the post-temozolomide recurrent tumour (S3). Scale bar, 50 µm.
