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Clinical Trial
. 2021 May 7:12:632547.
doi: 10.3389/fimmu.2021.632547. eCollection 2021.

Combination of Immunotherapy and Radiotherapy for Recurrent Malignant Gliomas: Results From a Prospective Study

Haihui Jiang  1   2 , Kefu Yu  3 , Yong Cui  1   2 , Xiaohui Ren  1   2 , Mingxiao Li  1   2 , Chuanwei Yang  1   2 , Xuzhe Zhao  1   2 , Qinghui Zhu  1   2 , Song Lin  1   2   4
Affiliations
Clinical Trial

Combination of Immunotherapy and Radiotherapy for Recurrent Malignant Gliomas: Results From a Prospective Study

Haihui Jiang et al. Front Immunol. .

Abstract

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.

Keywords: immuno-oncology; immunoadjuvant; immunotherapy; malignant gliomas; reirradiation.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Treatment scheme for patients enrolled in the present study.
Figure 2
Figure 2
The clinical efficacy of immunoadjuvant treatment and reirradiation in patients with recurrent WHO grade IV gliomas. (A) Waterfall plot showing the best tumor response in patients treated with immunoadjuvant therapy and reirradiation. (B) Swimmer plot showing disease status and survival time in 30 patients treated with immunoadjuvant therapy and reirradiation. (C) The median progression-free survival and overall survival of patients treated with immunoadjuvant therapy and reirradiation.
Figure 3
Figure 3
(A) Representative MR images of patients with different treatment responses. (B, C) Comparisons of survival rates between responders and non-responders. Responders showed a significantly longer progression-free survival (P < 0.0001) and overall survival (P=0.008) than non-responders.
Figure 4
Figure 4
Comparisons of immunological response between responders and non-responders. (A) In the subgroup of responders, the counts of CD8+ T cells and NK cells were significantly increased after receiving immunoadjuvant infusion (P < 0.05). (B) In the subgroup of non-responders, the counts of CD8+ T cells and NK cells were markedly decreased after receiving immunoadjuvant infusion (P < 0.05). *p < 0.05; ns, not significant.
Figure 5
Figure 5
(A) Oncoplot of significantly different mutations, CNVs and cytobands between the responder and non-responder subgroups. (B) Heatmap showing the z-scored mean marker expression of the panel markers for each PhenoGraph cluster. Clusters and markers are grouped by expression profiles. (C) t-SNE plots of 43071 subsampled single cells from each PhenoGraph cluster identified in the heatmap image. Cells are colored by samples and clusters. (D) Heatmap showing the z-score of the mean percentage of single-cell clusters in each sample. Clusters and patients are grouped by the densities of single-cell clusters. (E) Imaging mass cytometry analysis of the tumor immune microenvironment between responders and non-responders. The non-responders showed higher percentages of CD15+ (green) and CD68+ (red) cells than the responders (P < 0.001). ***p value < 0.001.
See this image and copyright information in PMC

References

    1. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. . CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol (2019) 21:v1–v100. 10.1093/neuonc/noz150 - DOI - PMC - PubMed
    1. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. . Effects of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy Alone on Survival in Glioblastoma in a Randomised Phase III Study: 5-Year Analysis of the EORTC-NCIC Trial. Lancet Oncol (2009) 10:459–66. 10.1016/S1470-2045(09)70025-7 - DOI - PubMed
    1. Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, et al. . Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA (2017) 318:2306–16. 10.1001/jama.2017.18718 - DOI - PMC - PubMed
    1. Jiang H, Zeng W, Ren X, Cui Y, Li M, Yang K, et al. . Super-Early Initiation of Temozolomide Prolongs the Survival of Glioblastoma Patients Without Gross-Total Resection: A Retrospective Cohort Study. J Neurooncol (2019) 144:127–35. 10.1007/s11060-019-03211-1 - DOI - PubMed
    1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. . Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med (2005) 352:987–96. 10.1056/NEJMoa043330 - DOI - PubMed

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