Combination Laser Therapy and Keytruda Significantly Increases Survival for Those with rHGA

Key Takeaways

• Laser interstitial thermal therapy (LITT) + Keytruda significantly improved median overall survival, progression-free survival, and 18-month survival compared with non-LITT surgery + Keytruda for people with recurrent high-grade astrocytoma.
• The findings support further study of the LITT + Keytruda combination as a potential immunotherapy-enhancing strategy in the salvage treatment of rHGA, where immune checkpoint inhibitors have historically shown limited efficacy.

A phase 1/randomized phase 2b trial (NCT02311582) published in Nature Communications found that laser interstitial thermal therapy (LITT)—performed with the NeuroBlate Laser Ablation System (Monteris Medical, Minnetonka, MN)—was associated with meaningful extensions in survival in participants with recurrent high-grade astrocytoma (rHGA) when used in combination with Keytruda (pembrolizumab; Merck, Rahway, NJ). The findings suggest that LITT may alter the tumor microenvironment in ways that enhance responsiveness to immune checkpoint inhibitors (ICIs) like Keytruda.

After the phase 1 dose-escalation lead-in study established a recommended dose of Keytruda (200 mg IV every 3 weeks), the randomized phase 2b study enrolled 45 participants with recurrent high-grade astrocytoma, including glioblastoma and World Health Organization (WHO) grade 3–4 astrocytoma. Participants were initially randomized 1:1 to receive LITT or non-LITT surgery (NLS) in addition to Keytruda. But after an interim review, the Data and Safety Monitoring Committee halted randomization, and all subsequent patients received LITT. The per-protocol cohort included 39 patients (LITT, n=33; NLS, n=6). The primary end point was progression-free survival (PFS), and the secondary end points included overall survival (OS), objective response rate, safety, and immune profiling via paired single-cell RNA sequencing and T-cell receptor sequencing of peripheral blood mononuclear cells.

Key outcomes from the per-protocol analysis included:​

• Median OS was 11.8 months with LITT + Keytruda vs 5.2 months with NLS + Keytruda (hazard ratio [HR], 0.17; 95% CI, 0.06 to 0.49; P=.0002).
• Median PFS was 4.5 months in LITT + Keytruda vs 1.6 months in NLS +Keytruda (HR, 0.21; 95% CI, 0.08 to 0.56; P=.0006).
• 18-month survival was 42% in the LITT arm vs 0% in the NLS arm.
• Disease control rate was 70% in the LITT arm, with 27% achieving partial response; all 6 NLS patients experienced disease progression.
• Treatment was well tolerated; grade 3-4 events were infrequent and resolved with intervention, and no grade 5 events occurred.
• LITT activated non-classical monocytes and, upon Keytruda initiation, prompted CD8⁺ T cell proliferation and clonal expansion; long-term survivors showed sustained central memory-to-effector CD8⁺ T cell transitions, while short-term survivors exhibited predominantly exhausted T cell phenotypes.

Source: Campian JL, Le SB, Ghiaseddin A, et al. Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a phase 1/randomized phase 2b trial. Nat Commun. 2026;17:1763. doi:10.1038/s41467-026-69522-w