Background: Randomized trials on the first-line treatment of high-risk neuroblastoma are limited. Therefore, we analyzed the national data base on the impact of I-131-meta-iodobenzylguanidine (mIBG) therapy, local radiotherapy, and single agent ch14.18 immunotherapy in the first-line therapy of high-risk neuroblastoma.
Methods: Patients of two consecutive national neuroblastoma trials were included if they met all key criteria: (1) stage 4 neuroblastoma, (2) age at diagnosis 18 months or older, (3) N5/N6 induction chemotherapy, (4) non-progressing residual mIBG positive metastatic disease after induction chemotherapy prior to myeloablative chemotherapy and autologous stem cell transplantation, (5) diagnosis between 1997 and 2012. mIBG therapy was scheduled for non-progressing MIBG positive lesions. Local radiotherapy 36-40 Gy was scheduled for mIBG positive residual at the primary site. Single agent ch14.18 was stratified according to open trials.
Results: A total of 232 patients were analyzed. The median observation time was 8.8 years. mIBG positive residual metastases were present prior to MAT in 92 patients. The median interval between mIBG therapy and stem cell transplantation was 21 days. The median mIBG activity applied was 7.4 GBq. The event-free survival was very similar between patients who underwent mIBG therapy (5yEFS 32.2+/-7.1%) compared to no mIBG therapy (5yEFS 27.9+/-6.9%, p=0.553). In contrast, a trend for better overall survival was found after mIBG therapy compared to no mIBG therapy (5yOS 58.1+/-7.6% vs. 38.9+/-7.5%, p=0.086). Multivariable analysis including MYCN, mIBG therapy, local radiotherapy, and immunotherapy with ch14.18 revealed an independent impact of MYCN amplification (p=0.028, hr 1.987) and ch14.18 treatment (p=0.004, hr 0.441) on EFS, and MYCN amplification (p<0.001, hr 3.476), ch14.18 treatment (p=0.008, hr 0.560), and mIBG therapy (p=0.047, hr 0.426) on OS.
Conclusions: mIBG therapy can improve survival in patients with incomplete metastatic response to induction chemotherapy. These results warrant a prospective multicenter trial on mIBG therapy. Moreover, this analysis confirmed the efficacy of immunotherapy with ch14.18.