Targeted radioimmunotherapy for embryonal tumor with multilayered rosettes.
PURPOSE
We explored the use of intraventricular 131I-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 131I-Omburtamab as a tracer followed by one or two therapeutic 131I-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 131I-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 131I-Omburtamab (80 and 53 mCi, respectively). Patient 3 had a local recurrence prior to 131I-Omburtamab treated with surgery, external beam radiation, chemotherapy, then 131I-Omburtamab (36 mCi). 131I-Omburtamab was well-tolerated. Mean dose delivered by 131I-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
131I-Omburtamab appears safe with favorable dosimetry therapeutic index. When used as consolidation following surgery and chemoradiation therapy, 131I-Omburtamab may have therapeutic benefit for patients with ETMR.
['Bailey|Kayleen|K|http://orcid.org/0000-0002-8193-642X', 'Pandit-Taskar|Neeta|N|', 'Humm|John L|JL|', 'Zanzonico|Pat|P|', 'Gilheeney|Stephen|S|', 'Cheung|Nai-Kong V|NV|', 'Kramer|Kim|K|http://orcid.org/0000-0002-3803-878X']
D000911:Antibodies, Monoclonal D058846:Antibodies, Monoclonal, Murine-Derived D001921:Brain D016543:Central Nervous System Neoplasms D002675:Child, Preschool D017809:Fatal Outcome D005260:Female D006801:Humans D007223:Infant D007276:Injections, Intraventricular D007457:Iodine Radioisotopes D008297:Male D009373:Neoplasms, Germ Cell and Embryonal D016499:Radioimmunotherapy D011874:Radiometry D013116:Spinal Cord
Radioimmunotherapy Embryonal tumor with multilayered rosettes 131I-Omburtamab ETMR 131I-8H9