Pre-radiation Nivolumab plus ipilimumab in patients with newly diagnosed high-grade gliomas.

Publication Title

Oncoimmunology

Authors

Santosh Kesari, Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute/Pacific Neuroscience Institute, 2200 Santa Monica Boulevard, Santa Monica, CA, 90404, USAFollow
Alexandre Wojcinski, Department of Translational Neurosciences and Neurotherapeutics, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United StateFollow
Sarabjot Pabla
R J Seager
Jaya Mini Gill, Pacific Neuroscience Institute, Neuro-Oncology, Santa Monica, CA, USA.Follow
Jose Carrillo, Pacific Neuroscience Institute, Santa Monica, California, USA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USAFollow
Naveed Wagle, Pacific Neuroscience Institute, Santa Monica, California, USA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USAFollow
David J. Park, Providence St. Jude Medical Center, Department of Hematology and Oncology, Fullerton, CA, USA.Follow
Minhdan Nguyen, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Judy D Truong, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Yuki Takasumi, Department of Pathology, Providence Saint John's Health Center, Santa Monica, CaliforniaFollow
Lisa Chaiken, Pacific Neuroscience Institute, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CaliforniaFollow
Shu-Ching Chang, Providence St. Vincent Medical Center, Clinical Research Program Services, Portland, OR, USA.Follow
Garni Barkhoudarian, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, California, USA.Follow
Daniel F Kelly, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, California, USA.Follow
Tiffany Juarez, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow

Document Type

Article

Publication Date

12-31-2024

Keywords

california; fullerton; sjmc; santa monica; psjhc; oregon; psvmc; Humans; Male; Female; Ipilimumab; Nivolumab; Middle Aged; Aged; Adult; Glioma; Brain Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Neoplasm Grading; Immune Checkpoint Inhibitors

Abstract

The limited success of immune checkpoint inhibitors (ICIs) in the adjuvant setting for glioblastoma highlights the need to explore administering ICIs prior to immunosuppressive radiation. To address the feasibility and safety of this approach, we conducted a phase I study in patients with newly diagnosed Grade 3 and Grade 4 gliomas. Patients received nivolumab 300 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity. Fifteen patients were treated, with four patients on dexamethasone at treatment initiation and five tumors having MGMT promoter methylated. Treatment began a median of 38 days post-surgery. The most common treatment-related adverse events (AEs) were rash, pruritus, fatigue, nausea, and anorexia. Grade 3 AEs were lipase increased (n = 2), anorexia (n = 1), pruritus (n = 1), and rash (n = 3), and one Grade 4 cerebral edema occurred. Median progression-free survival (mPFS) was 1.3 months and median overall survival (mOS) was 19.3 months (95% CI, 12.9-NA). Three patients deferred conventional radiochemotherapy for over seven months while ten eventually received it. Progressing tumors tended to exhibit higher LAG-3 levels at baseline compared to shrinking tumors. Analysis of paired pre-treatment and post-progression tissue (n = 5) showed trends of up-regulated TGF-β, ERBB2, ERBB3, and ERBB4 signaling pathways, downregulated PPAR signaling, decreased B cell proportions, and increased monocytes proportions in tumors post-treatment. We show nivolumab plus ipilimumab can be safely administered prior to standard radiotherapy for newly diagnosed gliomas and is operationally feasible. Clinicaltrials.gov NCT03425292 registered February 7, 2018.

Area of Special Interest

Neurosciences (Brain & Spine)

Area of Special Interest

Cancer

Specialty/Research Institute

Neurosciences

Specialty/Research Institute

Oncology

Specialty/Research Institute

Pharmacy

DOI

10.1080/2162402X.2024.2432728