PMID- 34025640 OWN - NLM STAT- MEDLINE DCOM- 20210917 LR - 20210917 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Combination of Immunotherapy and Radiotherapy for Recurrent Malignant Gliomas: Results From a Prospective Study. PG - 632547 LID - 10.3389/fimmu.2021.632547 [doi] LID - 632547 AB - BACKGROUND: World Health Organization (WHO) grade IV glioma remains one of the most lethal tumors with a dismal prognosis and inevitable recurrence. We evaluated the safety and efficacy of immunotherapy with radiotherapy in this population of patients. METHODS: This study was a single-arm, open-label, phase I trial based on patients with recurrent WHO grade IV glioma. Patients were treated with intracranial and systemic immunoadjuvants in combination with low-dose reirradiation. The primary endpoint of the present trial was safety. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). This trial is registered at ClinicalTrials.gov, NCT03392545. RESULTS: Thirty patients were enrolled. The most common adverse events (AEs) were fever (66.7%), vomiting (33.3%), headache (30.0%), and fatigue (23.3%). Only a single patient experienced grade 3 fever, and no grade 4 AEs or deaths related to treatment were observed. Of the 30 patients, 1 (3.3%) had a complete response, 5 (16.7%) had a partial response, 9 (30.0%) had stable disease, and 15 (50.0%) had progressive disease, resulting in an objective response rate of 20.0%. The median PFS of the entire cohort was 88.0 (61.0-254.0) days, and the median OS was 362.0 (197.0-601.0) days. Patients could be divided into responders and non-responders, and these groups exhibited a significant difference in terms of survival time, T lymphocyte subsets, frequency of cell division cycle 27 (CDC27) mutation status, and CD15 and CD68 expression (P<0.05). CONCLUSION: The combination of immunotherapy and radiotherapy is well tolerated and may provide clinical benefit for patients with recurrent WHO grade IV glioma. A prospective phase II study is needed to further validate the efficacy of our therapeutic regimen. CI - Copyright (c) 2021 Jiang, Yu, Cui, Ren, Li, Yang, Zhao, Zhu and Lin. FAU - Jiang, Haihui AU - Jiang H AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. FAU - Yu, Kefu AU - Yu K AD - Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. FAU - Cui, Yong AU - Cui Y AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. FAU - Ren, Xiaohui AU - Ren X AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. FAU - Li, Mingxiao AU - Li M AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. FAU - Yang, Chuanwei AU - Yang C AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. FAU - Zhao, Xuzhe AU - Zhao X AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. FAU - Zhu, Qinghui AU - Zhu Q AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. FAU - Lin, Song AU - Lin S AD - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. AD - National Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, China. AD - Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. LA - eng SI - ClinicalTrials.gov/NCT03392545 PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210507 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Adjuvants, Immunologic) SB - IM MH - Adjuvants, Immunologic/administration & dosage MH - Adult MH - Brain Neoplasms/immunology/pathology/*therapy MH - CD8-Positive T-Lymphocytes/immunology MH - Female MH - Glioma/immunology/pathology/*therapy MH - Humans MH - *Immunotherapy/adverse effects MH - Killer Cells, Natural/immunology MH - Male MH - Middle Aged MH - Mutation MH - *Neoplasm Recurrence, Local MH - Prognosis MH - Prospective Studies MH - *Radiotherapy/adverse effects MH - Survival Analysis PMC - PMC8138184 OTO - NOTNLM OT - immuno-oncology OT - immunoadjuvant OT - immunotherapy OT - malignant gliomas OT - reirradiation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/05/25 06:00 MHDA- 2021/09/18 06:00 PMCR- 2021/01/01 CRDT- 2021/05/24 08:04 PHST- 2020/11/23 00:00 [received] PHST- 2021/04/22 00:00 [accepted] PHST- 2021/05/24 08:04 [entrez] PHST- 2021/05/25 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.632547 [doi] PST - epublish SO - Front Immunol. 2021 May 7;12:632547. doi: 10.3389/fimmu.2021.632547. eCollection 2021.