Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma.

Abstract

The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, <i>P</i> < 0.0001; <i>HR</i> = 0.3) and mRANO (<i>P</i> < 0.0001; <i>HR</i> = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, <i>P</i> = 0.47; central, <i>P</i> = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (<i>P</i> = 0.017), but not central measurements (<i>P</i> = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (<i>R²</i> = 0.66, <i>P</i> < 0.0001) and centrally determined reads (<i>R²</i> = 0.57, <i>P</i> = 0.0007). No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between 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.