Vaccination In Situ Using Neoadjuvant PD-1 Blockade and Laser Interstitial Thermal Therapy in Recurrent High-Grade Glioma

Introduction: Immune checkpoint inhibitors induce potent responses against systemic cancer though clinical responses against primary malignant brain tumors have been disappointing, in part due to poor T-cell immunogenicity and infiltration behind the BBB. Laser interstitial thermal therapy (LITT) induces coagulative necrosis of tumor and disrupts the peritumoral BBB. When leveraged with immune checkpoint inhibition, combination therapy may potentiate the egress of tumor antigens for epitope spread with a concurrent increase in brain-infiltrating effector CD8+ T cells. We present a case series of seven patients with recurrent high-grade glioma treated with neoadjuvant anti-PD-1 and LITT.

Methods: We retrospectively reviewed seven patients treated at NYU Langone Health between 2019-2023 with GBM (n=5) and IDH mutant astrocytoma (n=2). Disease burden was followed radiographically through volume segmentation of treated and non-contiguous satellite lesions overtime. Patients were followed for progression-free survival (PFS) and overall survival (OS).

Results: Patients (n=7) were aged 34-64 (5 male, 2 female), and had biopsy-confirmed recurrent GBM (n=5) and IDH mutant astrocytoma (n=2). Of the 6 patients analyzed, mean tumor volume was 9.87 cm3 (range 2.95 – 24.40 cm3). All patients received neoadjuvant anti-PD-1, and 5 of them also received adjuvant pembrolizumab. At 5–7-month follow-up, 4/6 patients were identified as responders with a mean reduction in overall tumor burden of 70.65% (range 31.9 – 89.5%) compared to 2 non-responders whose disease burden increased by a mean of 614.5%. Two of the 4 responders showed regression of three non-contiguous, satellite lesions. At long-term follow-up, tumor burden of satellite lesions reduced by a mean of 90% (range 70-100%). Median PFS was 358 days (range 153-994 days) and median OS was 405 days (range 160-1227 days).

Conclusion : PD-1 blockade and LITT resulted in radiographic tumor regression in patients with recurrent high-grade glioma, including LITT-naïve satellite tumor deposits. This observation suggests that LITT-induced cell death may be antigenic and can be exploited to leverage immune checkpoint blockade against recurrent tumors. The underlying mechanisms and predictive biomarkers should be further investigated.