Abstract
Background: The prognosis of children with diffuse intrinsic pontine glioma (DIPG) remains dismal despite radio- and chemotherapy or molecular-targeted therapy. Immunotherapy is a powerful and promising approach for improving the overall survival (OS) of children with DIPG. Methods: A retrospective analysis for feasibility, immune responsiveness, and OS was performed on 41 children treated in compassionate use with multimodal therapy consisting of Newcastle disease virus, hyperthermia, and autologous dendritic cell vaccines as part of an individualized combinatorial treatment approach for DIPG patients. Results: Patients were treated at diagnosis (n = 28) or at the time of progression (n = 13). In the case of 16 patients, histone H3K27M mutation was confirmed by analysis of biopsy (n = 9) or liquid biopsy (n = 9) specimens. PDL1 mRNA expression was detected in circulating tumor cells of ten patients at diagnosis. Multimodal immunotherapy was feasible as scheduled, until progression, in all patients without major toxicity. When immunotherapy was part of primary treatment, median PFS and OS were 8.4 m and 14.4 m from the time of diagnosis, respectively, with a 2-year OS of 10.7%. When immunotherapy was given at the time of progression, median PFS and OS were 6.5 m and 9.1 m, respectively. A longer OS was associated with a Th1 shift and rise in PanTum Detect test scores. Conclusions: Multimodal immunotherapy is feasible without major toxicity, and warrants further investigation as part of a combinatorial treatment approach for children diagnosed with DIPG.
Highlights
Diffuse intrinsic pontine glioma (DIPG) is a rare brainstem tumor that typically occurs in children.The overall incidence rate of all primary brain tumors ranges between 3–6 per 100,000 children and Medicines 2020, 7, 29; doi:10.3390/medicines7050029 www.mdpi.com/journal/medicinesMedicines 2020, 7, 29 adolescents between 0 and 19 years of age [1,2]
Forty-one children (n = 10 male, 31 female) from 16 countries were effectively treated with multimodal immunotherapy at the Immun-Onkologisches Zentrum Köln (IOZK), following an in-depth explanation of the treatment strategy and written informed consent from the patient or patient’s guardian
The treated children were subdivided into three groups: Group 1, children receiving immunotherapy before radio- and chemotherapy (n = 6); Group 2, children receiving immunotherapy in conjunction with the first line of treatment provided by the local oncology center (n = 22 total; radiotherapy only = 13, radiotherapy and chemotherapy = 9); and Group 3, children treated with immunotherapy upon disease progression following the first line of standard treatment, which consisted of radiotherapy for all patients, and a combination of radio/chemotherapy in the case of nine patients (n = 13 total)
Summary
Diffuse intrinsic pontine glioma (DIPG) is a rare brainstem tumor that typically occurs in children.The overall incidence rate of all primary brain tumors ranges between 3–6 per 100,000 children and Medicines 2020, 7, 29; doi:10.3390/medicines7050029 www.mdpi.com/journal/medicinesMedicines 2020, 7, 29 adolescents between 0 and 19 years of age [1,2]. Diffuse intrinsic pontine glioma (DIPG) is a rare brainstem tumor that typically occurs in children. The overall incidence rate of all primary brain tumors ranges between 3–6 per 100,000 children and Medicines 2020, 7, 29; doi:10.3390/medicines7050029 www.mdpi.com/journal/medicines. About 10–15% of these tumors are located in the brain stem [2,3] and 75–80% of pediatric brainstem tumors are DIPG [3], making its incidence less than one per 100,000 children each year. But not all, of these lesions are driven by histone mutations [5], classifying them as diffuse midline gliomas (DMG), according to the current. About 85% of DIPGs harbor histone mutations [7]. The prognosis of children with diffuse intrinsic pontine glioma (DIPG). Immunotherapy is a powerful and promising approach for improving the overall survival (OS) of children with DIPG
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