Abstract
PURPOSE: We explored the use of intraventricular (131)I-Omburtamab targeting B7-H3 in patients with ETMR. METHODS: Patients were enrolled in an IRB approved, phase 1, 3 + 3 dose escalation trial. Patients with CNS disease expressing the antibody target antigen B7-H3 were eligible. We report on a cohort of three patients with ETMR who were enrolled on the study. Three symptomatic children (ages 14 months, 3 and 3.5 years) had large parietal masses confirmed to be B7-H3-reactive ETMR. Patients received 2 mCi (131)I-Omburtamab as a tracer followed by one or two therapeutic (131)I-Omburtamab injections. Dosimetry was based on serial CSF, blood samplings and region of interest (ROI) on nuclear scans. Brain and spine MRIs and CSF cytology were done at baseline, 5 weeks after (131)I-Omburtamab, and approximately every 3 months thereafter. Acute toxicities and survival were noted. RESULTS: Patients received surgery, focal radiation, and high dose chemotherapy. Patients 1 and 2 received (131)I-Omburtamab (80 and 53 mCi, respectively). Patient 3 had a local recurrence prior to (131)I-Omburtamab treated with surgery, external beam radiation, chemotherapy, then (131)I-Omburtamab (36 mCi). (131)I-Omburtamab was well-tolerated. Mean dose delivered by (131)I-Omburtamab was 68.4 cGy/mCi to CSF and 1.95 cGy/mCi to blood. Mean ROI doses were 230.4 (ventricular) and 58.2 (spinal) cGy/mCi. Patients 1 and 2 remain in remission 6.8 years and 2.3 years after diagnosis, respectively; patient 3 died of progressive disease 7 months after therapy (2 years after diagnosis). CONCLUSIONS: (131)I-Omburtamab appears safe with favorable dosimetry therapeutic index. When used as consolidation following surgery and chemoradiation therapy, (131)I-Omburtamab may have therapeutic benefit for patients with ETMR.