Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial

authors

• Mackay Alan
• Burford Anna
• Molinari Valeria
• Jones David T.W.
• Izquierdo Elisa
• Brouwer-Visser Jurriaan
• Giangaspero Felice
• Haberler Christine
• Pietsch Torsten
• Jacques Thomas
• Figarella-Branger Dominique
• Rodriguez Daniel
• Morgan Paul
• Raman Pichai
• Waanders Angela
• Resnick Adam
• Massimino Maura
• Garrè Maria Luisa
• Smith Helen
• Capper David
• Pfister Stefan
• Würdinger Thomas
• Tam Rachel
• Garcia Josep
• Thakur Meghna Das
• Vassal Gilles
• Grill Jacques
• Jaspan Tim
• Varlet Pascale
• Jones Chris

keywords

• Immune
• CD8
• MAPK
• Hypermutator
• H3F3A
• Pediatric high-grade glioma

document type

abstract

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term “HGG” in the pediatric population.

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