Predictors of response, progression‐free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high‐risk neuroblastoma

Purpose The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. Methods A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). Results Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five‐year progression‐free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG‐avid lesions (100% MIBG trials; 84% non‐MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 ( P  < 0.001), lower Curie score ( P  = 0.003), no measurable CT/MRI lesions ( P  = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials ( P  = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS ( P  < 0.001). In multivariable analysis, MYCN amplification ( P  = 0.037) was associated with worse PFS; measurable CT/MRI lesions ( P  = 0.041) were associated with worse OS; prior progressive disease (PD; P  < 0.001/ P  < 0.001), Curie score ≥ 1 ( P  < 0.001; P  = 0.001), higher Curie score ( P  = 0.048/0.037), and treatment on non‐PBSC trials ( P  = < 0.001/0.003) were associated with worse PFS and OS. Conclusions NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.