ID #1200 Ribociclib and Temozolomide Is Feasible and Safe in a Young Adult with Diffuse Hemispheric Glioma, H3 G34-mutant

Background

Diffuse hemispheric glioma H3 G34-mutant(DHG), is an infiltrative glioma involving the cerebral hemispheres, characterized by a missense mutation of the H3-3A gene. DHG has a median progression-free survival of 9 months and median overall survival of 18-22 months. Standard treatment remains maximal safe resection followed by chemoradiotherapy, and subsequent chemotherapy. Liu et al.[1] described CDK6 as a promising target leading to development of a clinical trial. We describe a young adult with DHG and rapid progression after chemoradiation treated with ribociclib and temozolomide.

Methods

Case Report

Results

Patient presented at 33 years old with left sided weakness and was found to have multifocal FLAIR hyperintense lesions in the right cerebral hemisphere. Patient underwent biopsy and subtotal resection with histopathology most consistent with a high-grade glioma. Next Generation Sequencing revealed H3F3A p.G35R and TP53 mutations with an integrated molecular diagnosis of diffuse hemispheric glioma H3 G34-mutant. Patient received post-operative focal proton beam radiation 59.4 Gy with concurrent temozolomide(75 mg/m^2). Patient then began adjuvant temozolomide (150 mg/m^2) and Boswellia. After 1 cycle, patient developed new seizures, and imaging demonstrated significantly increased FLAIR hyperintensity concerning for worsening tumor, although concurrent posttreatment changes couldn’t be excluded. Patient then began 4 week cycles of combination treatment with ribociclib(days 1-21, 600 mg) and temozolomide(days 1-5, 150 mg/m^2 cycle 1, 200 mg/m^2 cycles 2-5, 150 mg/m^2 cycles 6-10) along with Boswellia. At the time of submission, patient has received 10 cycles and remains with stable disease both clinically and radiographically. Adverse events attributed to therapy include nausea and 1 cycle delayed due to uncomplicated neutropenia that resolved with dose reduction of temozolomide dosing from 200 mg/m^2 to 150 mg/m^2.

Conclusion

This is the first detailed report of combination ribociclib with temozolomide in DHG and builds upon prior literature supporting ribociclib as a potential treatment for DHG.

1. Liu I, Alencastro Veiga Cruzeiro G, Bjerke L, Rogers RF, Grabovska Y, Beck A, Mackay A, Barron T, Hack OA, Quezada MA, Molinari V, Shaw ML, Perez-Somarriba M, Temelso S, Raynaud F, Ruddle R, Panditharatna E, Englinger B, Mire HM, Jiang L, Nascimento A, LaBelle J, Haase R, Rozowsky J, Neyazi S, Baumgartner AC, Castellani S, Hoffman SE, Cameron A, Morrow M, Nguyen QD, Pericoli G, Madlener S, Mayr L, Dorfer C, Geyeregger R, Rota C, Ricken G, Ligon KL, Alexandrescu S, Cartaxo RT, Lau B, Uphadhyaya S, Koschmann C, Braun E, Danan-Gotthold M, Hu L, Siletti K, Sundström E, Hodge R, Lein E, Agnihotri S, Eisenstat DD, Stapleton S, King A, Bleil C, Mastronuzzi A, Cole KA, Waanders AJ, Montero Carcaboso A, Schüller U, Hargrave D, Vinci M, Carceller F, Haberler C, Slavc I, Linnarsson S, Gojo J, Monje M, Jones C, Filbin MG. GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant. Cancer Cell. 2024 Aug 27:S1535-6108(24)00305-2. doi: 10.1016/j.ccell.2024.08.006. Epub ahead of print. PMID: 39232581; PMCID: PMC11865364.