NIMG-28. VALIDATION OF MODIFIED RESPONSE ASSESSMENT IN NEURO ONCOLOGY (mRANO) DETERMINED PFS AS A STRONG PREDICTOR OF OVERALL SURVIVAL IN RECURRENT GLIOBLASTOMA TREATED WITH A TARGETED IMMUNOTOXIN

INTRODUCTION The current study compared the modified response assessment in neuro-oncology (mRANO)(1), iRANO (2), and standard RANO criteria (3) as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). METHODS A total of 47 patients with rGBM were enrolled in a phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and an independent radiologic faculty (IRF), then standard RANO, iRANO, and mRANO criteria were applied. Differences of PFS and the association between PFS and OS were evaluated. RESULTS 41 of 47 patients were evaluable for response. Both local site and IRF-determined PFS was significantly shorter using standard RANO compared to iRANO (log-rank, P< 0.0001; HR=0.3) and mRANO (P< 0.0001; HR=0.3). No difference in PFS was observed between iRANO and mRANO (Local, P=0.67; IRF, P=0.59). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (Local, P=0.47; IRF, P=0.34). Using the iRANO, a weak association driven by a few outliers was observed between confirmed PFS and OS via local site measurements (P=0.017), but not central IRF measurements (P=0.18). Importantly, 24 of 41 patients (59%) were censored using iRANO and not included because they did not have confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2=0.66, P< 0.0001) and IRF-determined reads (R2=0.57, P=0.0007). CONCLUSION No correlation between PFS and OS was observed for standard RANO or iRANO, but a strong correlation was identified between both locally-determined and centrally-determined PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.