Survival outcomes in patients with high-risk neuroblastoma (HRNB) in remission after relapsed or refractory treatment receiving eflornithine (DFMO) maintenance.

10060 Background: Five-year overall survival in newly diagnosed HRNB patients is around 50%, with relapse as the primary cause of mortality. While survival for newly diagnosed HRNB has improved with new treatment advances, relapsed or refractory (R/R) patients continue to have poor outcomes, with a high risk of subsequent relapse even among those who achieve remission, underscoring the need for treatments to improve EFS in this group. DFMO has been evaluated as a chemopreventative therapy in a single arm phase 2 study designed to compare Event Free Survival (EFS) and Overall Survival (OS) outcomes with published data for HRNB. The results of patients treated after standard therapy have been previously published. We now present an analysis of EFS/OS for patients with R/R disease, who historically have had a two-year EFS of approximately 10%. Methods: A total of 140 HRNB patients were enrolled, prospectively divided into two strata. S1 included patients in initial remission after upfront therapy, whereas S2 included patients who had either relapsed or had disease refractory to standard induction chemotherapy but achieved remission with additional therapy. Patients received 2 years of continuous treatment with oral DFMO 750 ±250 mg/m 2 BID and were followed for up to 7 years. Results: A total of 35 patients withR/R disease who had achieved remission after additional therapy were enrolled onto S2, including 28 patients in remission after one or more prior relapses and 7 refractory patients in remission after subsequent therapies. Of the relapsed patients, 23 had one prior relapse, while 5 patients had two or more relapses prior to enrollment; only one previously relapsed patient had received chemoimmunotherapy prior to enrollment in the study. For the entireS2 cohort, two-year EFS was 46% (95% CI 29%, 61%) with the lower confidence interval above the 10% historical control estimate. Four-year EFS was 46% (95% CI 29%, 61%) and OS 62% (95% CI 44%, 76%), with no relapses occurring after 18 months. For patients enrolled with refractory disease only (n=7) the four-year EFS was 85.7%. In the 28 relapsed patients, the four-year EFS was 35.7%, with single relapse patients (n=23) having an EFS rate of 39.1% and multiple relapsed patients (n=5) 20.0%. Conclusions: Patients in remission after chemotherapy for relapsed or refractory HRNB and treated with DFMO had improved EFS compared to the best historical estimate available at the time of the study. Although the number of patients is too small to support clear conclusions, the subgroup of refractory patients had outcomes that trended better than the relapsed subgroup with an EFS rate that was unexpectedly similar to prior reports of DFMO-treated S1 patients in remission after standard upfront therapy. Clinical trial information: NCT02395666 , NCT00026312 .