Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti-B7H3 immunotherapy

AbstractOmburtamab is a B7H3-specific murine monoclonal antibody. B7H3 (CD 276) is a member of the B7 family of immune checkpoint co-inhibitory receptors overexpressed on many human malignancies. Radioimmunotherapy with124I- or131I-omburtamab administered in the cerebrospinal fluid (CSF), intraperitoneal or intratumoral cavity is currently under investigation for the treatment of CNS malignancies. The immunologic effects of anti-B7H3 therapy are not fully elucidated. A 6-year-old male was diagnosed with metastates of neuroblastoma to the received intraventricular131I-omburtamab on an IRB-approved protocol. A treatment cycle consisted of a 2  mCi dosimetry dose and a 50 mCi treatment dose. Dosimetry by serial imaging, pharmacokinetics and safety were investigated. Clinical status, magnetic resonance imaging, CSF cell count and cytology were evaluated pre- and post-131I-omburtamab at 5 and 26  weeks. The patient did well with cycle 1. Three hours after the dosimetry dose of cycle 2, he developed a fever (39 °C), chills and headache. Blood and CSF samples were sent for culture. CSF was notable for nucleated cell pleocytosis with profound mast cell proliferation consistent with chemical meningitis. He was treated with supportive care; symptoms resolved over 48 h. Further therapy with131I-omburtamab was electively discontinued. CSF cell count 5  weeks later demonstrated resolution of CSF pleocytosis. Local–regional administration of intraventricular131I-omburtamab targeti...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research