NorthWest Biotherapeutics Inc (NWBO)

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https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.2043
2022 ASCO Annual Meeting I
CENTRAL NERVOUS SYSTEM TUMORS

DOI: 10.1200/JCO.2022.40.16_suppl.2043 Journal of Clinical Oncology - published online before print June 2, 2022

A single-institution, retrospective examination of new contrast enhancement, progression, and pseudoprogression in IDH mutant glioma.

Ethan Wetzel, Blaine S.C. Eldred, Vicki Liu, Serendipity Zapanta Rinonos, Negar Khanlou, Linda M. Liau, Phioanh Leia Nghiemphu, Timothy Francis Cloughesy, Benjamin M. Ellingson, Albert Lai

2043

Background:
IDH mutant glioma patients are followed by MRI, where new contrast enhancement (CEnew) is a hallmark of tumor progression. Interpretation of CEnew is confounded by pseudoprogression (PsP), the appearance of CEnew that spontaneously resolves on subsequent scans.
PsP has been characterized in IDH wildtype patients, but is poorly understood in the IDH mutant category. This study represents an examination of the characteristics and impacts on patient survival of CEnew in IDH mutant gliomas.
Methods: Of the 724 confirmed IDH mutant glioma patients treated at UCLA between 1998 and 2022, 587 were included (median follow-up = 5.23 years). Patients were excluded based on these criteria: <4 MRI scans, unknown IDH status, and unknown WHO 2016 diagnosis. CEnew was first identified by direct review of images and confirmed by the radiology report.
Any new enhancement appearing on the first post surgical MRI was not considered CEnew.
CEnew was interpreted as progression after surgical resection indicating tumor or the re-initiation of chemotherapy or radiation and was considered PsP after the resolution of enhancement without new treatment initiation.
Some PsP patients could have received bevacizumab.
Kaplan-Meier survival analyses were used to examine overall survival differences between groups.

Results: 327 of 587 patients developed CEnew. The incidence of CEnew was higher in Grade 4 Astrocytoma (G4 Astro) versus all other pathologies and lowest in LO (p < 0.05). The Enhancement Free Survival (EFS) was shortest for G4 Astro patients (p =.002); LO patients had the longest median EFS of 2602 days (p = 0.002).
The development of CEnew and presence of preoperative enhancement were both found to be negative survival prognosticators in all pathologies (p < 0.05).
From our analysis, 92 patients developed PsP and 177 developed progression. The median duration of a PsP spot was 244 days. PsP spots appeared earlier than progression spots (median 538 vs 1113 days, p =.001).
The incidence of PsP was highest in the G4 Astro group and lowest in LO patients.
Survival analysis of patients with progression versus those with PsP and progression shows PsP is associated with longer OS in the entire cohort and the LO, AO, AA, and G4 Astro groups (p < 0.05).
100% of PsP patients received radiation therapy (RT).
The median time from the end of RT to PsP was 209 days. Conclusions: While CEnew in IDH mutant gliomas is associated with reduced OS, poorer outcome is driven by progressors. PsP represents 28% of CEnew instances, typically occurs within 1 year of RT and have superior outcome to progressors and equivalent to of patients that do not display CEnew.