Academic Journal
Pre-radiation Nivolumab plus ipilimumab in patients with newly diagnosed high-grade gliomas
| العنوان: | Pre-radiation Nivolumab plus ipilimumab in patients with newly diagnosed high-grade gliomas |
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| المؤلفون: | Santosh Kesari, Alexandre Wojcinski, Sarabjot Pabla, R. J. Seager, Jaya M. Gill, Jose A. Carrillo, Naveed Wagle, David J. Park, Minhdan Nguyen, Judy Truong, Yuki Takasumi, Lisa Chaiken, Shu-Ching Chang, Garni Barkhoudarian, Daniel F. Kelly, Tiffany M. Juarez |
| المصدر: | OncoImmunology, Vol 13, Iss 1 (2024) |
| بيانات النشر: | Taylor & Francis Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Glioblastoma, glioma, immune checkpoint blockade, neoadjuvant, pre-radiation, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162402X 2162-402X 68770243 |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2024.2432728 |
| URL الوصول: | https://doaj.org/article/ae68770243fe4ed9a2afd9d7e559875b |
| رقم الانضمام: | edsdoj.68770243fe4ed9a2afd9d7e559875b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2162402X 68770243 |
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| DOI: | 10.1080/2162402X.2024.2432728 |