Artikel
Fractionated intracavitary radioimmunotherapy with Lu-177 labeled 6A10 Fab fragments in patients with glioblastoma – first patient experience
Fraktionierte intrakavitäre Radioimmuntherapie mit Lu-177-markierten 6A10-Fab-Fragmenten bei Patienten mit Glioblastom: erste klinische Erfahrungen
Suche in Medline nach
Autoren
Veröffentlicht: | 25. Mai 2022 |
---|
Gliederung
Text
Objective: After surgical cytoreduction and standard radiochemotherapy of glioblastoma, approved maintenance therapies are lacking. In line with the infiltrative biology of this tumor type, most recurrences are seen around the resection cavity. Adjuvant radio-immunotherapy (RIT) with Lu-177 labeled 6A10-Fab fragments, targeting tumor-associated carbonicanhydrase XII (CA12), applied into the resection cavity, offers a promising strategy to address this hibernating tumor burden. We report on the first in human application.
Methods: A 41-year-old patient had undergone microsurgical resection for an IDH-1-mutated glioblastoma. After completion of standard radiochemotherapy the patient showed stable disease with minimal FET-uptake and contrast enhancement on follow-up FET-PET/MRI, i.e. no visible residual tumor. Based on an interdisciplinary tumor board decision fractionated intracavitary radioimmunotherapy with Lu-177 labeled 6A10 Fab fragments was offered as compassionate use. After implantation of an injection reservoir into the tumor cavity, three consecutive doses of Lu-177 labeled 6A10 Fab fragments were administered over three months, corresponding to 25% - 50% - 25% of a total activity of 592 MBq. Injected dose was adapted according to the size of the resection cavity. A dosimetry protocol was performed with planar whole-body scintigraphy and SPECT/CT of the abdomen, approx. 2h, 24h, 48h, 72h and 7-10 days after injection.
Results: No toxicity according to CTCAE version 6.0 or other adverse events were observed. Dosimetry did not reveal absorbed doses above the upper dose limit for organs at risk. For the kidneys, the estimated absorbed dose was approximately 3.7 mGy/MBq and for the hematopoietic bone marrow 0.04 mGy/MBq. The tumor remains stable at 6 months after RIT and 20 months after initial diagnosis.
Conclusion: Intracavitary radioimmunotherapy with Lu-177 labeled 6A10-Fab fragments appears to be a safe maintenance therapy for glioblastoma patients, albeit only assessed in a single patient so far. A multicenter confirmatory phase-I-trial will be initiated soon to determine the maximum tolerated dose and safety of adjuvant radio-immunotherapy with Lu-177 labeled 6A10-Fab fragments.