Background: The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is still dismal. The role of iodine-131 meta-iodobenzylguanidine (131I-mIBG) treatment as a tool to reduce tumour burden before novel immunotherapies is not defined. Patients and methods: Patients with R/R NB were included in a prospective observational study based on two infusions of 131I-mIBG plus melphalan (110 mg/m2), supported by autologous haematopoietic stem cell rescue. The activity of the first administration was 444 MBq (12 mCi/kg), while the second dose was modulated to reach a whole-body absorbed dose of 4 Gy. The International Neuroblastoma Response Criteria (INRC) were used for response. Results: Twenty-six patients with a median age of 5.9 years (range 2.5-17.2 years) were treated. Twenty-three patients presented a bone/bone marrow involvement, and 21 patients presented an uptake at primary site or at soft-tissue sites. The median International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) skeletal score was 10 (range 1-70). The main recorded toxicities were haematological, with no toxic deaths and only one grade 4 mucositis. Hypothyroidism was reported in 6 patients of the 14 alive patients. The overall response rate was 48% [95% confidence interval (CI) 28% to 69%] with only one progression; after treatment the median SIOPEN skeletal score was 6 (range 0-70) with a median reduction of 35% (range 4.3%-100%). Overall, 52% (95% CI 32% to 73%) of patients achieved/maintained a SIOPEN skeletal score <7 and a soft-tissue lesion <5 cm was seen in 67% (95% CI 43% to 91%). After this treatment, 65% of patients underwent GD2-targeting chimeric antigen receptor (CAR)-T-cell therapy and 50%, high-dose chemotherapy with busulfan and melphalan. The 3-year overall survival was 55% (95% CI 33% to 73%) and event-free survival was 42% (95% CI 23% to 60%). Conclusion: The 131I-mIBG therapy plus melphalan is confirmed to be effective to reduce/control tumour burden. Further studies are needed to clarify the role and timing of this treatment and to integrate its role in the strategy of CAR-T cells.
De Ioris, M. A., Villani, M. F., Fabozzi, F., Del Bufalo, F., Altini, C., Cefalo, M. G., Cannata, V., Del Baldo, G., Pizzoferro, M., Alessi, I., Lanzaro, F., Davide, C., Toma, P., D'Andrea, M. L., Di Giannatale, A., Serra, A., Mastronuzzi, A., Garganese, M. C., Locatelli, F., 131I-mIBG therapy in relapsed/refractory neuroblastoma: an old bridge to the future, <<ESMO OPEN>>, 2025; 10 (4): 1-7. [doi:10.1016/j.esmoop.2025.104541] [https://hdl.handle.net/10807/330059]
131I-mIBG therapy in relapsed/refractory neuroblastoma: an old bridge to the future
Mastronuzzi, Angela;Locatelli, Franco
2025
Abstract
Background: The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is still dismal. The role of iodine-131 meta-iodobenzylguanidine (131I-mIBG) treatment as a tool to reduce tumour burden before novel immunotherapies is not defined. Patients and methods: Patients with R/R NB were included in a prospective observational study based on two infusions of 131I-mIBG plus melphalan (110 mg/m2), supported by autologous haematopoietic stem cell rescue. The activity of the first administration was 444 MBq (12 mCi/kg), while the second dose was modulated to reach a whole-body absorbed dose of 4 Gy. The International Neuroblastoma Response Criteria (INRC) were used for response. Results: Twenty-six patients with a median age of 5.9 years (range 2.5-17.2 years) were treated. Twenty-three patients presented a bone/bone marrow involvement, and 21 patients presented an uptake at primary site or at soft-tissue sites. The median International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) skeletal score was 10 (range 1-70). The main recorded toxicities were haematological, with no toxic deaths and only one grade 4 mucositis. Hypothyroidism was reported in 6 patients of the 14 alive patients. The overall response rate was 48% [95% confidence interval (CI) 28% to 69%] with only one progression; after treatment the median SIOPEN skeletal score was 6 (range 0-70) with a median reduction of 35% (range 4.3%-100%). Overall, 52% (95% CI 32% to 73%) of patients achieved/maintained a SIOPEN skeletal score <7 and a soft-tissue lesion <5 cm was seen in 67% (95% CI 43% to 91%). After this treatment, 65% of patients underwent GD2-targeting chimeric antigen receptor (CAR)-T-cell therapy and 50%, high-dose chemotherapy with busulfan and melphalan. The 3-year overall survival was 55% (95% CI 33% to 73%) and event-free survival was 42% (95% CI 23% to 60%). Conclusion: The 131I-mIBG therapy plus melphalan is confirmed to be effective to reduce/control tumour burden. Further studies are needed to clarify the role and timing of this treatment and to integrate its role in the strategy of CAR-T cells.
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