Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab

Helen Hwang, Jiayi Huang, Karam Khaddour, Omar H Butt, George Ansstas, Jie Chen, Ruth Gn Katumba, Albert H Kim, Eric C Leuthardt, Jian L Campian, Helen Hwang, Jiayi Huang, Karam Khaddour, Omar H Butt, George Ansstas, Jie Chen, Ruth Gn Katumba, Albert H Kim, Eric C Leuthardt, Jian L Campian

Abstract

Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) and laser interstitial thermal therapy in a case series of patients with recurrent IDH-wild-type glioblastoma.

Trial registration: ClinicalTrials.gov NCT02311582.

Keywords: glioblastoma; immune checkpoint inhibitors; immunotherapy; laser interstitial thermal therapy; pembrolizumab.

Conflict of interest statement

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.. T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) (upper…
Figure 1.. T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) (upper panel) and T1 weighted contrast enhancement (lower panel) brain MRI images taken at different times before and after laser interstitial thermal therapy treatment for patient 1.
The patient's baseline scan showed tumor progression. He received LITT followed by pembrolizumab. Pseudoprogression was noted and tested by repeat LITT with biopsy. Partial response was seen in the subsequent scans. The patient's last MRI showed further progression of disease. LITT: Laser interstitial thermal therapy.
Figure 2.. A representative image of the…
Figure 2.. A representative image of the resection specimen at initial diagnosis of patient 1 showing pleomorphic glial cells with palisading necrosis consistent with glioblastoma.
(A) A biopsy taken after recurrence (22 months after the initial LITT treatment) shows large areas of geographic necrosis (red arrows) and many hyalinized vessels (black arrows) consistent with treatment effect. (B) Tumor cells are also present. LITT: Laser interstitial thermal therapy.
Figure 3.. Swimmer plots for recurrent glioblastoma…
Figure 3.. Swimmer plots for recurrent glioblastoma patients receiving laser interstitial thermal therapy and pembrolizumab.
Bar length indicates duration of response and survival since receiving treatment at recurrence. RT: Radiation therapy; TMZ: Temozolomide.

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Source: PubMed

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