Neoadjuvant PD1 blockade with laser interstitial thermal therapy for recurrent high-grade glioma

While immune checkpoint inhibitors (ICI) induce potent responses against several systemic malignancies, clinical efficacy against high-grade glioma has been limited by immunosuppression, low mutational burden and limited lymphocyte infiltration into tumors. Laser interstitial thermal therapy (LITT) induces coagulative necrosis and disrupts the peritumoral blood-brain barrier (BBB), creating a potentially antigenic milieu. We hypothesized that neoadjuvant and adjuvant ICI would synergize with LITT to potentiate antitumor immune responses and enhance survival.

This retrospective study is an exploratory case series that includes 9 adult patients with recurrent IDH wild-type glioblastoma (GBM, n = 6), IDH mutant high-grade astrocytoma (n = 2) and H3K27M mutant diffuse midline glioma (n = 1). All patients received neoadjuvant anti-PD1 ICI prior to LITT and most received adjuvant ICI (8/9). Disease burden was followed through radiographic volume segmentation of gadolinium-enhancing disease. Patients were followed for progression-free (PFS) and overall survival (OS).

Patients (age 29-64 years; 7 male, 2 female) had pre-operative mean tumor volumes of 11.15 cm³ (range 2.93-26.09 cm³). Mean ablation volume was 12.08 cm³ (range 5.14-18.60 cm³). There were no perioperative complications. All patients showed an initial increase in gadolinium-enhancing volume after LITT. Seven of 9 (78 %) patients demonstrated subsequent regression in total gadolinium-enhancing volume. Three non-contiguous satellite lesions naïve to laser ablation exhibited complete or near-complete regression in 2 patients. Median PFS was 5.90 months (range 1.00-41.23), and median OS was 9.97 months (range 1.20-41.23).

Combination therapy with neoadjuvant and adjuvant pembrolizumab and LITT is feasible and safe in recurrent high-grade glioma. Responses may be more robust in certain molecular subtypes of glioma. Further studies are needed to investigate this potential synergy.