Clinical and Biological Features of Response in Resistant Neuroblastoma to 131I-Metaiodobenzylguanidine Radiotherapy in the Anti-GD2 Immunotherapy Era.
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BACKGROUND: 131I-metaiodobenzylguanidine (131I-MIBG) radiotherapy is a key treatment for relapsed and refractory (R/R) neuroblastoma (NB). Patients with R/R disease treated in the modern era are increasingly exposed to anti-GD2 immunotherapy, which exerts selective pressure and may modify both tumor cell state and microenvironment. However, response rates to 131I-MIBG in the anti-GD2 era are unknown, and the factors associated with response are poorly defined. PROCEDURE: We retrospectively quantified objective response rates (ORR) to 131I-MIBG and evaluated the association between clinical and molecular features-including receipt of anti-GD2 immunotherapy-and ORR among participants with R/R NB from 2011 to 2023. Variables with an unadjusted odds ratio [uOR] p < 0.2 in a univariable screen were included in multivariable analysis. RESULTS: A total of 125 participants with relapsed (60.8%) or refractory (39.2%) NB were included. Fifty-eight (46.4%) previously received anti-GD2 antibody therapy. Forty-seven (37.6%) achieved an objective response to 131I-MIBG therapy, 56 had stable disease (SD; 44.8%), and 22 had progressive disease (17.6%). Compared to immunotherapy-naïve participants (ORR 35.8%), participants who previously received anti-GD2 therapy (39.7%, uOR 1.18 [0.57-2.4]) and specifically chemoimmunotherapy (37.5%, 0.99 [0.42-2.26]) had similar rates of response to 131I-MIBG. Asians compared to Whites (adjusted OR 0.21 [0.05-0.95]), no bone marrow disease (0.17 [0.06-0.50]), and higher Curie score (0.90 [0.83-0.98]) were significantly associated with lower odds of response. CONCLUSION: Prior exposure to anti-GD2 therapy was not associated with differential response to 131I-MIBG. ORR in this modern cohort was comparable to that reported in previous studies. Participants with bone marrow disease and a lower Curie score have a significantly higher ORR to 131I-MIBG therapy.