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Targeted radioimmunotherapy for embryonal tumor with multilayered rosettes

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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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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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Authors and Affiliations

  1. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA

    Kayleen Bailey, Stephen Gilheeney, Nai-Kong V. Cheung & Kim Kramer

  2. Department of Radiology (Molecular Imaging and Therapy Service), Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Neeta Pandit-Taskar

  3. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    John L. Humm & Pat Zanzonico

Authors
  1. Kayleen Bailey
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  2. Neeta Pandit-Taskar
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  3. John L. Humm
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  4. Pat Zanzonico
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  5. Stephen Gilheeney
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  6. Nai-Kong V. Cheung
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  7. Kim Kramer
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Corresponding author

Correspondence to Kim Kramer.

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Conflict of interest

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.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Research involving animal rights

There were no animals involved.

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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

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