Association of response with survival in patients with relapsed/refractory high-risk neuroblastoma: A report from NANT Consortium.

10033 Background: Patients with relapsed/refractory (RR) high-risk neuroblastoma (HR-NB) have poor survival. Tumor response may be an early predictive endpoint, though response may not reflect long term survival. We evaluated the association between NANT Response Criteria (NANTRC) v1.2/2.0 with event-free survival (EFS) and overall survival (OS) in patients with RR-NB treated on contemporary NANT Phase 1/2 trials. Methods: Patients enrolled on 8 NANT trials from 2013 to 2022 were included. For patients enrolled on more than one trial, the first trial data was included. NANTRC were utilized to grade individual response components (soft tissue [ST], bone/MIBG, bone marrow [BM]) and overall response (complete [CR], partial [PR], minor [MR] response, stable disease [SD], or progressive disease [PD]). Patient/tumor characteristics, prior therapy and relapse, and disease at enrollment were analyzed for association with best overall response (BOR). Component and BOR were analyzed for association with EFS and OS from trial treatment initiation. EFS and OS were compared with the log-rank test and estimated by the Kaplan-Meier methods. Results: Among 244 patients, 3-year OS was 52% (95% confidence interval [CI] 46-58%), and EFS was 22% (95% CI 14-32%). OS differed significantly by best overall response (p<0.001), driven primarily by inferior outcomes of patients with PD. The 3-year OS was 16% (95% CI 9-29%) for patients with PD. Patients achieving objective response (CR/PR/MR) had an OS of 63% (95% CI 55-74%) and EFS 25% (95% CI 15-43%), while those achieving disease control (CR/PR/MR/SD) had very similar OS of 63% (95% CI 57-71%) and EFS 29% (95% CI 20-43%). Among patients with response of CR, PR, MR, or SD, OS and EFS were not significantly different. For individual components, a similar impact on OS was seen for PD vs no PD (all p<0.001), with BOR of PD in MIBG/bone and ST having OS <10%. Patients lacking either BM or bone/MIBG involvement (but not ST) at baseline and remained not involved in those components demonstrated superior OS (both p<0.001). Patients with BOR of PD had shorter time from diagnosis to first progression (median of 1.4 vs 1.8 years, p=0.035), and higher incidence of MYCN -amplified disease (46% vs. 14%, p<0.001) and prior history of progression (95% vs 73%, p<0.001). Conclusions: In RR-HRNB treated on contemporary NANT trials, BOR of PD is associated with inferior OS. Patients achieving disease control (CR/PR/MR/SD) experienced comparable outcomes regardless of response achieved. These findings support disease-control as a clinically meaningful efficacy endpoint for early-phase neuroblastoma trials. 3-year survival by component response. Component Response N OS % (95% CI) EFS* % (95% CI) BM Non-PD 100 47 (38, 58) 17 (7, 38) PD 18 29 (14, 61) - Bone/MIBG Non-PD 180 59 (52, 66) 22 (13, 35) PD 30 7 (2, 26) - ST Non-PD 142 61 (53, 70) 28 (18, 44) PD 35 9 (3, 25) - *EFS censored at time of new therapy.