783 Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: a report from the International RRD consortium

BackgroundResponse to immune checkpoint inhibition (ICI) is encouraging for patients with progressive, DNA replication-repair deficient, high-grade glioma (RRD-HGG).1 However, the clinical outcomes and biological mechanisms for subsequent immune-directed salvage approaches after progression on anti-...

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Published in:Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 1), p.A880-A880
Main Authors: Das, Anirban, Fernandez, Nicholas, Levine, Adrian, Bianchi, Vanessa, Stengs, Lucie, Edwards, Melissa, Pugh, Trevor, Tsang, Derek, Ertl-Wagner, Birgit, Morgenstern, Daniel, Hawkins, Cynthia, Bouffet, Eric, Tabori, Uri
Format: Article
Language:English
Subjects:
Biomarkers
Colorectal cancer
Consortia
Genetic disorders
Glioma
Immunotherapy
Radiation
Regular and Young Investigator Award Abstracts
Toxicity
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Summary:BackgroundResponse to immune checkpoint inhibition (ICI) is encouraging for patients with progressive, DNA replication-repair deficient, high-grade glioma (RRD-HGG).1 However, the clinical outcomes and biological mechanisms for subsequent immune-directed salvage approaches after progression on anti-PD1 monotherapy remain unknown.MethodsThe International RRD Consortium performed a registry study of patients managed using central molecular, genomic, radiological review and treatment recommendations between 2015–2021. Treatment after progression on anti-PD1 monotherapy included re-irradiation where feasible, and continuation of anti-PD1 with either anti-CTLA4 (ipilimumab), or a MEK-inhibitor (trametinib). Outcomes included radiological response (iRANO), toxicity, second progression-free (PFS2) and overall survival (OS2). Companion biomarkers were analyzed centrally.ResultsAmong 75 patients with RRD-HGG receiving PD-1 blockade, 20 remain progression-free at a median follow-up of 44.6-months. For 55 patients with 2nd-relapse/progressive tumors, continuation of ICI (n=38) resulted in median OS2 of 11.6-months (51% alive) versus 1.2-months when ICI was discontinued (n=17; no survivors, p
ISSN:2051-1426
DOI:10.1136/jitc-2023-SITC2023.0783