213 A Positive Impact on Patterns of Relapse in Diffuse Intrinsic Pontine Glioma after Convection-Enhanced Delivery of Omburtamab

Abstract

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) carries a high mortality rate secondary to its aggressive molecular characteristics, infiltrative nature, and lack of effective treatment options. Overall survival is only 9-11 months and median time to progression after radiotherapy is 5-6 months. Convection-enhanced delivery (CED) has demonstrated safety in phase-1 trials, but efficacy is indeterminate. METHODS: Sixty-three children with DIPG treated between 2010-2022 were retrospectively reviewed for first radiographic progression. All were treated using conventional external beam radiation (EBRT) and 31 (49%) were treated with CED of radiolabeled 124-Iodine-Omburtamab following EBRT (NCT01502917). Progression was codified by independent neuroradiologists according to anatomic location (local, contiguous, medulla, midbrain, middle cerebellar peduncle (MCP), and/or distant). Overall survival (OS) was assessed with Kaplan-Meier methodology and cumulative incidence of progression at each anatomic site was assessed in a cause-specific competing risk analysis with death as a competing event and were stratified based on CED treatment. RESULTS: Mean age at diagnosis was 7.1 (+/-3.4 years) with a median OS of 1.22 years for the cohort. Patients receiving CED demonstrated higher rates of progression in general, when considering progression at all anatomical sites (HR 1.79, p = 0.047) and no statistically significant difference was found in OS when stratified by CED treatment (p = 0.22). However, CED treatment was associated with significantly lower cumulative incidence of pontine and medullary progression (HR 0.43, p = 0.03; HR 0.15, p = 0.01, respectively) relative to non-CED treated patients. No statistically significant differences in progression were identified at other sites (contiguous, midbrain, MCP, or distant). CONCLUSIONS: MR-defined patterns of relapse provide evidence for locoregional control in children with DIPG treated with radioimmunotherapy administered by CED. These results prompt a consideration for modifying the design of future clinical trials by supplementing brain stem CED with whole neuroaxis treatment.