INNV-20. RADIOGRAPHIC RESPONSE AND SEIZURE CONTROL IN IDH1 MUTANT GLIOMA PATIENTS USING IVOSIDENIB
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2021-11-12
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<jats:title>Abstract</jats:title> <jats:p>Isocitrate dehydrogenase 1 (IDH1) is commonly mutated in grade II-III gliomas, and the mutant enzyme leads to the production of the oncometabolite 2-hydroxyglutarate (2-HG). 2-HG is responsible for the gliomagenesis associated with these tumors and the promotion of seizures via glutamate receptors. Ivosidenib, a small molecule oral mIDH1 inhibitor, has shown promise in clinical trials to treat IDH1 mutant gliomas, and providers can utilize this agent in IDH1 mutant glioma patients. We evaluated our IDH1 mutant glioma patients treated off-label with ivosidenib and described the radiographic response and seizure control in this cohort when ivosidenib was initiated between October 2020 to February 2021. Radiographic response was determined using RANO criteria, and seizure control was determined by comparing seizures per month before and after initiation of ivosidenib. All patients represented received single-agent ivosidenib dosed at 500 mg orally once a day. One patient required a dose reduction to 250 mg orally once a day because of drug-induced diarrhea. In our cohort of six patients, patient age range was 31 to 74 years with four female patients and two male patients. Diagnoses represented were astrocytoma, IDH1 mutant (n=3) oligodendroglioma (WHO), IDH1 mutant, 1p19q co-deleted (n=2), and anaplastic astrocytoma IDH1 mutant (n=1). Three patients experienced a reduction of seizure frequency, two patients did not have seizures before or after therapy, and one patient remained with the same level of seizures (1 seizure/month). Radiographic responses recorded included three patients with stable disease, two patients with minor responses, and one patient with a partial response. Treatment with ivosidenib is ongoing for this cohort of mIDH1 glioma patients. Updated information on prolonged disease control and seizure control in this cohort of IDH1 mutant glioma patients will be presented. Therapeutics, such as ivosidenib, can lead to improved seizure control and radiographic outcomes in IDH1 mutant glioma patients.</jats:p>
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Peters, Katherine, Mallika Patel, Candice Alford, Gerardo Chavez, Jung-Young Kim, Jennifer Durling, Tracy Novack, Kristen Batich, et al. (2021). INNV-20. RADIOGRAPHIC RESPONSE AND SEIZURE CONTROL IN IDH1 MUTANT GLIOMA PATIENTS USING IVOSIDENIB. Neuro-Oncology, 23(Supplement_6). pp. vi109–vi109. 10.1093/neuonc/noab196.431 Retrieved from https://hdl.handle.net/10161/24050.
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Margaret Johnson
I am a neuro-oncologist, neurologist, and palliative care physician at the Preston Robert Tisch Brain Tumor Center. I also provide neuro-oncology expertise for the National Tele-Oncology Program and National Precision Oncology Program at the Veteran's Health Administration. My clinical and research interests encompass supportive care and palliative care with a special interest in older adults with brain tumors. The incidence of malignant brain tumors like glioblastoma and non-malignant tumors like meningioma affect aging populations and it is crucial to be able to provide better care for these patients.
Daniel Bryce Landi
Mustafa Khasraw
I am a physician-scientist with a background in medical oncology and neuro-oncology, with affiliations to multiple departments, research, and training programs at Duke.
I lead a Tumor Immunobiology Laboratory where we use various wet and dry lab techniques to understand the interactions between tumors and the immune system. Our goal is to identify vulnerabilities that can be targeted for novel therapies.
I serve as the Deputy Director of the Center for Cancer Immunotherapy at the Duke Cancer Institute where we are tasked to facilitate clinical research and translate promising discoveries made by scientists across various departments and cancer types at Duke, particularly in the field of immune and T cell-based therapies.
My team and our laboratory operate in an environment that enables the transition from bench-side basic scientific discoveries to clinical trials, and back to the bench ensuring the evaluation of new treatments for cancer patients.
David Michael Ashley
My career in cancer research dates more than two decades. I am credentialed in both pediatric and adult neuro-oncology practice and this has been the focus of my efforts in translational research and leadership. As evident from my publication and grant support record, my primary academic focus has been on neurologic tumors, the development of innovative therapies and approaches to care. These efforts have included basic and translational laboratory research. My experience includes moving laboratory findings in brain tumor immunology and epigenetics into early phase clinical trials. I have expertise in immuno-oncology, having developed and clinically tested dendritic cell vaccines and other immuno-therapeutics. My achievements in research have led to change in practice in the care of children and adults with brain tumors, including the introduction of new standards of practice for the delivery of systemic therapy. I am highly regarded for this work, as evidenced by numerous invitations to plenary sessions and symposia of international standing. I have been the principal investigator of a number of important national and international studies, both clinical and pre-clinical. I am recognized as a senior figure and opinion leader in neuro-oncology nationally and internationally. I have held several significant leadership roles, including Director of two major cancer centers, I served as the Chair of Medicine at Deakin University, the Program Director of Cancer Services at University Hospital Barwon Health, and Executive Director of the Western Alliance Academic Health Science Centre (Australia). I began my current position as Director of The Preston Robert Tisch Brain Tumor Center, Head, Preuss Laboratory, in March 2018. In this role, I am responsible for the clinical care, research, and educational program related to Brain Tumor Center. I am also a senior investigational neuro-oncologist within the adult brain tumor program at Duke.
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