Retrospective review of safety and efficacy of programmed cell death-1 inhibitors in refractory high grade gliomas

Abstract

BackgroundProgrammed cell death ligand-1 (PD-L1) expression has been reported in up to 61% of high grade gliomas (HGG). The purpose of this study was to describe safety and efficacy of PD-1 inhibition in patients with refractory HGGs.MethodsThis Institutional Review Board approved single center retrospective study included adult patients with pathologically confirmed HGG who received a PD-1 inhibitor from 9/2014–10/2016 outside of a clinical trial at Memorial Sloan Kettering Cancer Center.ResultsTwenty five HGG patients received pembrolizumab as part of a compassionate use program. Median age was 50 years (range 30–72); 44% were men; 13 had glioblastoma (52%), 7 anaplastic astrocytoma (28%), 2 anaplastic oligodendroglioma (8%), 2 unspecified HGG (8%), and 1 gliosarcoma (4%). Median prior lines of treatments were 4 (range 1–9). Nineteen (76%) previously failed bevacizumab. Median KPS was 80 (range 50–100). Concurrent treatment included bevacizumab in 17 (68%) or bevacizumab and temozolomide in 2 (8%) patients. Median number of doses administered was 3 (range 1–14). Outcomes were assessed in 24 patients. PD-1 inhibitor related adverse events included LFT elevations, hypothyroidism, diarrhea, myalgias/arthralgias, and rash. Best radiographic response was partial response (n = 2), stable disease (n = 5), and progressive disease (n = 17). Median progression free survival (PFS) was 1.4 months (range 0.2–9.4) and median overall survival (OS) was 4 months (range 0.5–13.8). Three-month PFS was 12% and 6-month OS was 28%.ConclusionWhile response rates are low, a few patients had a prolonged PFS. Pembrolizumab was tolerated with few serious toxicities, even in patients receiving concomitant therapy.

The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas

“…Recently, the discovery of immune checkpoint molecules, such as programmed death-1 (PD-1) protein and its ligand, namely, programmed death-ligand 1 (PD-L1), has provided novel therapeutic targets. Considering the lack of effective treatments for gliomas, immunotherapy, especially anti-PD-1/PD-L1 antibodies, has brought hope for brain malignances (11,12). In fact, PD-L1 expression on the surface of tumor cells, one of the potential indicators for checkpoint inhibitor use (13), was found to be detectable in a portion of glioma patients (14,15).…”

Long noncoding RNA CASC9/miR‐519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis

“…Glioma, accounting for 70% of brain tumours, causes thousands of cancer‐related death worldwide. Despite the combination therapy, eg, surgical excision, chemotherapy, and radiotherapy, have significantly improved the long‐term curative effect and prognosis, the survival rate and curative ratio is still pessimistic . Glioma is characterized by high invasive and diffusion, yet the potential mechanisms remain far from understanding .…”

Applied Precision Cancer Medicine in Neuro-Oncology

“…Pembrolizumab has been suggested in patients with tumour expression of PD-L1 or with a hypermutability. In a small study of 25 patients with refractory high-grade glioma, pembrolizumab was administered as salvage treatment and achieved a median overall survival of four months 25 . In May 2017, the FDA granted accelerated approval to pembrolizumab for the first tissue-agnostic indication in patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumours that have progressed following prior treatment and which have no satisfactory alternative treatment options 26 .…”