Abstract
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.
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References
Niguez BF, Martínez-Lage JF, Almagro MJ et al (2010) Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update. Childs Nerv Syst 26:1003–1008
Spence T, Sin-Chan P, Picard D et al (2014) CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity. Acta Neuropathol 128:291–303
Mozes P, Hauser P, Hortobágyi T et al (2016) Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR). J Neurooncol 126:99–105
Eberhart CG, Brat DJ, Cohen KJ, Burger PC (2000) Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes. Pediatr Dev Pathol 3:346–352
Manjila S, Ray A, Hu Y, Cai DX, Cohen ML, Cohen AR (2011) Embryonal tumors with abundant neuropil and true rosettes: 2 illustrative cases and a review of the literature. Neurosurg Focus 30:E2
Horwitz M, Dufour C, Leblond P et al (2016) Embryonal tumors with multilayered rosettes in children: the SFCE experience. Childs Nerv Syst 32:299–305
Jaramillo S, Grosshans DR, Philip N et al (2019) Radiation for ETMR: literature review and case series of patients treated with proton therapy. Clin Transl Radiat Oncol 15:31–37
Padovani L, André N, Constine LS, Muracciole X (2012) Neurocognitive function after radiotherapy for paediatric brain tumours. Nat Rev Neurol 8:578–588
Modak S, Kramer K, Gultekin SH, Guo HF, Cheung NK (2001) Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. Cancer Res 61:4048–4054
Ahmed M, Cheng M, Zhao Q et al (2015) Humanized affinity-matured monoclonal antibody 8H9 has potent antitumor activity and binds to FG loop of tumor antigen B7-H3. J Biol Chem 290:30018–30029
Souweidane MM, Kramer K, Pandit-Taskar N et al (2018) Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial. Lancet Oncol 19:1040–1050
Miraldi FD, Nelson AD, Kraly C et al (1986) Diagnostic imaging of human neuroblastoma with radiolabeled antibody. Radiology 161:413–418
Kramer K, Humm JL, Souweidane MM et al (2007) Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. J Clin Oncol 25:5465–5470
Chi SN, Zimmerman MA, Yao X et al (2009) Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27:385–389
Kramer K, Pandit-Taskar N, Zanzonico P et al (2015) Low incidence of radionecrosis in children treated with conventional radiation therapy and intrathecal radioimmunotherapy. J Neurooncol 123:245–249
Acknowledgements
We thank Mr. Joseph Olechnowicz for editorial assistance, Dr Serge Lyashchenko, HiJin Park, Jiong Wu for radiochemistry assistance. We are grateful to our patients and families for allowing us to participate in their clinical care. The authors acknowledge support from the NIH Cancer Center Support Grant P30 CA008748.
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Dr. N.K. Cheung reports: receiving commercial research grants from Y-mabs Therapeutics and Abpro-Labs Inc., holding ownership interest/equity in Y-Mabs Therapeutics Inc., holding ownership interest/equity in Abpro-Labs, and owning stock options in Eureka Therapeutics. NKC is the inventor and owner of issued patents licensed by MSK to Ymabs Therapeutics, Biotec pharmacon, and Abpro-labs. NKC is a consultant/advisory board member for Abpro-Labs and Eureka Therapeutics. Dr. Pat Zanzonico is the inventor on a patent pending for systems and methods for determining optimum patient-specific antibody dose for tumor targeting. Dr. Kim Kramer is a consultant to Ymabs Therapeutics Inc. 8H9 is currently licensed to Ymabs Therapeutics. Data in this report was acquired prior to their sponsorship of this study.
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Bailey, K., Pandit-Taskar, N., Humm, J.L. et al. Targeted radioimmunotherapy for embryonal tumor with multilayered rosettes. J Neurooncol 143, 101–106 (2019). https://doi.org/10.1007/s11060-019-03139-6
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DOI: https://doi.org/10.1007/s11060-019-03139-6