Background: ASCT improves event-free survival (EFS) for HR-NB. Pilot studies suggest that intensification of myeloablative therapy using tandem ASCT further improves outcome for HR-NB. We conducted a multicenter RCT comparing tandem vs. single consolidation in patients with HR-NB. Methods: Between 11/2007 and 2/2012, 652 eligible patients (pts) with newly diagnosed HR-NB received induction therapy: 6 cycles of chemotherapy including initial 2 cycles of dose-intensive cyclophosphamide/topotecan followed by PBSC collection. Randomization occurred at end induction to single ASCT with carboplatin-etoposide-melphalan (CEM) or tandem ASCT with thiotepa–cyclophosphamide ASCT followed by a modified CEM (TC:CEM). HR pts with non-MYCN amplified Stage 3 (age>18mos) or Stage 4 (age 12-18 mos) tumors were non-randomly assigned to single ASCT (CEM). EFS and overall survival (OS) were analyzed as intent-to-treat. Results: Median age at study entry was 3.1 yrs, 88% (n=574 pts) had Stage 4 disease and 38.2% (n=249 tumors) had MYCN amplification. A total of 355 pts were randomized (CEM n=179 pts; TC:CEM n=176 pts) and 27 patients were non-randomly assigned to CEM. Of randomized pts, 249 patients received post-consolidation immunotherapy on COG trials. Treatment-related mortality was 2.6% (Induction n=7 [1%]; Consolidation n=10 [2.8%; n=8 CEM, n=2 TC:CEM]). Rates of severe mucosal, infectious or liver toxicities were similar between arms. 3-year EFS and OS from diagnosis were 51.1±2.0% and 68.2±1.9%, respectively. EFS and OS for randomized cohort are shown in the Table. Conclusions: Tandem myeloablative consolidation therapy improves survival probability in patients with high-risk neuroblastoma, especially in the setting in post-consolidative immunotherapy. Clinical trial information: NCT00567567.CohortsN3-yr EFS
+/- SE (%)2-sided
p-value3-yr OS
+/- SE (%)2-sided
p-valueCEM17948.8 ± 4.069.0 ± 3.6TC:CEM17661.8 ± 4.10.008273.8 ± 3.70.2563ImmunotherapyCEM12955.4 ± 4.675.7 ± 3.9TC:CEM12073.7 ± 4.40.000986.3 ± 3.40.0158