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Background Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO), a small molecule oral mIDH1 inhibitor, is FDA-approved for mIDH1 newly diagnosed and relapsed/refractory acute myeloid leukemia. Moreover, IVO has efficacy in clinical trials for recurrent mIDH1 gliomas. Given the lack of targeted treatments for gliomas, we initiated off-label IVO for mIDH glioma patients in October 2020. Methods Retrospectively, we sought to assess early outcomes in our patients and describe their experience on IVO from October 2020 through February 2022. Our objective was to report on the following variables of off-label use of IVO: radiographic response, seizure control, tolerability, and access to the medication. All patients initially received single-agent IVO dosed at 500 mg orally once daily. Results The cohort age range was 21–74 years. Tumor types included astrocytoma (n = 14) and oligodendroglioma (n = 16), with most being grade 2 (n = 21). The best radiographic response in nonenhancing disease (n = 22) was 12 stable diseases, 5 minor responses, 3 partial responses, and 2 progressive diseases. Seizure frequency was stable to improved for most patients (70%, n = 21). IVO was well-tolerated, with the most common toxicities being diarrhea, elevated creatine kinase, and QTc interval prolongation. Most patients (66.7%, n = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%. Conclusions Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a fatal brain tumor with limited treatment options. O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is the central molecular biomarker linked to both the response to temozolomide, the standard chemotherapy drug employed for GBM, and to patient survival. However, MGMT status is captured on tumor tissue which, given the difficulty in acquisition, limits the use of this molecular feature for treatment monitoring. MGMT protein expression levels may offer additional insights into the mechanistic understanding of MGMT but, currently, they correlate poorly to promoter methylation. The difficulty of acquiring tumor tissue for MGMT testing drives the need for non-invasive methods to predict MGMT status. Feature selection aims to identify the most informative features to build accurate and interpretable prediction models. This study explores the new application of a combined feature selection (i.e., LASSO and mRMR) and the rank-based weighting method (i.e., MGMT ProFWise) to non-invasively link MGMT promoter methylation status and serum protein expression in patients with GBM. Our method provides promising results, reducing dimensionality (by more than 95%) when employed on two large-scale proteomic datasets (7k SomaScan® panel and CPTAC) for all our analyses. The computational results indicate that the proposed approach provides 14 shared serum biomarkers that may be helpful for diagnostic, prognostic, and/or predictive operations for GBM-related processes, given further validation. [ABSTRACT FROM AUTHOR]

The lack of treatments with durable response in neuro-oncology highlights the critical need for clinical trials to advance patient care. The intersection of relatively low incidence, evolving classification schema, and entrenched community, healthcare provider, and organizational factors have been historic challenges against successful trial enrollment and implementation. The additional need for multidisciplinary, often tertiary-level care, further magnifies latent national and international health inequities with rural and under-served populations. The COVID-19 pandemic both unveiled fundamental weaknesses in historical approaches and prompted the necessity of new approaches and systems for conducting clinical trials. Here, we provide an overview of traditional barriers to clinical trial enrollment in neuro-oncology, the effect of COVID-19 on these barriers, and the discovery of additional systemic weaknesses. Finally, we discuss future directions by reflecting on lessons learned with strategies to broaden access of care and streamline clinical trial integration into clinical practice. [ABSTRACT FROM AUTHOR]