Response‐adapted consolidation therapy strategy for patients with metastatic high‐risk neuroblastoma: Results of the SMC NB‐2014 study

Background Tandem high‐dose chemotherapy and autologous stem cell transplantation (HDCT/auto‐SCT) and incorporation of 131 I‐metaiodobenzylguanidine ( 131 I‐MIBG) treatment have shown positive outcomes in high‐risk neuroblastoma. However, more optimized treatment strategies are still needed. Procedure The NB‐2014 study was a nonrandomized, prospective trial that examined survival outcomes in metastatic high‐risk neuroblastoma patients using response‐adapted consolidation therapy. We used post‐induction residual 123 I‐MIBG status at metastatic sites as a treatment response marker. Patients achieving complete resolution of MIBG uptake at metastatic sites underwent a reduced first HDCT/auto‐SCT with a 20% dose reduction in HDCT. After the first HDCT/auto‐SCT, patients with remaining MIBG uptake received dose‐escalated (18 mCi/kg) 131 I‐MIBG treatment. In contrast, those with complete resolution of MIBG at metastatic sites received a standard dose (12 mCi/kg) of 131 I‐MIBG. We compared survival and toxicity outcomes with a historical control group from the NB‐2009. Results Of 65 patients treated, 63% achieved complete resolution of MIBG uptake at metastatic sites following induction chemotherapy, while 29% of patients still had MIBG uptake at metastatic sites after the first HDCT/auto‐SCT. The 3‐year event‐free survival (EFS) and overall survival (OS) rates were 68.2% ± 6.0% and 86.5% ± 4.5%, respectively. Compared to NB‐2009, EFS was similar ( p = .855); however, NB‐2014 had a higher OS ( p = .031), a lower cumulative incidence of treatment‐related mortality ( p = .036), and fewer acute and late toxicities. Conclusions Our results suggest that response‐adaptive consolidation therapy based on chemotherapy response at metastatic sites facilitates better treatment tailoring, and appears promising for patients with metastatic high‐risk neuroblastoma.