A phase II study of radioimmunotherapy with intraventricular I-3F8 for medulloblastoma.

TitleA phase II study of radioimmunotherapy with intraventricular I-3F8 for medulloblastoma.
Publication TypeJournal Article
Year of Publication2018
AuthorsKramer K, Pandit-Taskar N, Humm JL, Zanzonico PB, Haque S, Dunkel IJ, Wolden SL, Donzelli M, Goldman DA, Lewis JS, Lyashchenko SK, Khakoo Y, Carrasquillo JA, Souweidane MM, Greenfield JP, Lyden D, De Braganca KD, Gilheeney SW, Larson SM, Cheung N-KV
JournalPediatr Blood Cancer
Date Published2018 Jan
KeywordsAdolescent, Adult, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Agents, Immunological, Cerebellar Neoplasms, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Injections, Intraventricular, Iodine Radioisotopes, Male, Medulloblastoma, Radioimmunotherapy, Survival Rate

BACKGROUND: High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular I-labeled 3F8 in patients with MB on a phase II clinical trial.

METHODS: Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) I-3F8 or I-3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) I-3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region-of-interest analyses on serial imaging scans. Disease evaluation included pre- and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6-12 months thereafter.

RESULTS: Forty-three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment-related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0-2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3-55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18-0.88, P = 0.024).

CONCLUSIONS: cRIT with I-3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high-risk or recurrent MB.

Alternate JournalPediatr Blood Cancer
PubMed ID28940863
PubMed Central IDPMC6692907
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States