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Panobinostat in adults with H3 K27M-mutant diffuse midline glioma: a single-center experience
Bryan J Neth1, Samantha N Balakrishnan2, Ivan D Carabenciov3,2
1Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Neth.Bryan@mayo.edu.
Introduction:
Diffuse midline gliomas (DMG) with the H3 K27M-mutation are a well-described entity with most DMG harboring this mutation, with notable heterogeneity in adults. No therapy has been proven to improve survival in this tumor type. Panobinostat is a histone deacetylase inhibitor that may have therapeutic benefit.
Methods:
We report our retrospective experience with use of panobinostat in adults (> 18 years) with H3 K27M-mutant DMG treated at Mayo Clinic (Rochester) from January 2016 to August 2020, with follow-up until October 2021. Survival was calculated using the Kaplan-Meier method.
Results:
4 patients with H3 K27M-mutant glioma were treated with panobinostat as compassionate use. Patients had a median age of 40 years (range 22-62 years) and 2 were female. Tumor location was midline for all patients, spinal cord (n = 2), brainstem (n = 1), and thalamus (n = 1). All tumors were IDH1/IDH2 wildtype. 3 patients received radiotherapy followed by adjuvant panobinostat. All patients had no other pharmacologic therapy utilized prior to or during panobinostat therapy aside from concurrent dexamethasone utilized in 3 patients. No patient experienced a grade 2 or higher (per CTCAE grade) adverse effect. The median overall survival was 42 months, median progression free survival of 19 months, 2 patients were alive at last follow up (both with spinal cord tumors and received radiation). The best response was stable disease in 2 patients and a partial response in 1 patient.
Conclusions:
This is the first report of clinical outcomes of panobinostat in adults with H3 K27M-mutant DMG. We showed that it is well-tolerated at the dosage schedule that we describe, with no serious adverse effects throughout the study period.
Insights
Panobinostat, a histone deacetylase inhibitor, showed promising results in treating diffuse midline gliomas (DMG) with the H3 K27M-mutation in adults. This study found the treatment well-tolerated with no serious adverse effects, suggesting potential therapeutic benefit for this rare tumor type.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Pharmacology
Background:
- Diffuse midline gliomas (DMG) with H3 K27M-mutation are aggressive brain tumors with limited treatment options.
- No current therapy has demonstrated improved survival for patients with DMG.
- Panobinostat, a histone deacetylase inhibitor, presents a potential therapeutic avenue due to its mechanism of action.
Purpose of the Study:
- To evaluate the clinical outcomes and safety of panobinostat in adult patients with H3 K27M-mutant DMG.
- To assess the tolerability and efficacy of panobinostat in this patient population.
Main Methods:
- Retrospective case series of 4 adult patients with H3 K27M-mutant DMG treated with panobinostat at Mayo Clinic (2016-2020).
- Patients received panobinostat as compassionate use, with some undergoing prior radiotherapy.
- Survival outcomes were analyzed using the Kaplan-Meier method.
Main Results:
- The median overall survival was 42 months, and median progression-free survival was 19 months.
- Two patients remained alive at last follow-up, both with spinal cord tumors who received radiation.
- The treatment was well-tolerated, with no grade 2 or higher adverse events reported.
Conclusions:
- This is the first report on the clinical outcomes of panobinostat in adult H3 K27M-mutant DMG.
- Panobinostat demonstrated good tolerability at the described dosage schedule in this patient cohort.
- The findings suggest panobinostat as a potentially safe treatment option for H3 K27M-mutant DMG.
