Reinfusion of unprocessed, granulocyte colony-stimulating factor-stimulated whole blood allows dose escalation of ¹⁸⁶relabeled chimeric monoclonal antibody U36 radioimmunotherapy in a phase I dose escalation study

Purpose: In an earlier Phase I radioimmunotherapy (RIT) study with rhenium-186-labeled chimeric monoclonal antibody (cMAb) U36 in patients with refractory head and neck squamous cell carcinoma, the maximum tolerated activity was established at 1.0 GBq/m², at which bone marrow doses ranged from 0.7 to 1.1 Gy. In the present study, further dose escalation in RIT was evaluated using a facile method of reinfusion of granulocyte colony-stimulating factor (G-CSF)-stimulated unprocessed whole blood. Experimental Design: Nine patients with recurrent or metastatic head and neck squamous cell carcinoma were treated at radiation dose levels of 1.0, 1.5, and 2.0 GBq/m². Before RIT, G-CSF (10 μg/kg/day) was administered s.c. at home during 5 days. On day 6, just before administration of ¹⁸⁶Relabeled cMAb U36, 1 liter of whole blood was harvested and kept unprocessed at 4°C until reinfusion after 72 h. Blood samples were taken for analysis of pharmacokinetics and bone marrow dosimetry. Patients were evaluated for myelotoxicity and tumor response. Results: Blood harvesting, RIT, and reinfusion of whole blood were well tolerated by all patients. G-CSF stimulation resulted in a mean of 0.41 × 10⁶ CD34⁺ cells/kg (range, 0.15-0.83 × 10⁶ CD34⁺ cells/kg) and a mean committed colony-forming units granulocyte macrophage count of 5.62 × 10⁴/kg (range, 0.62-13.37 × 10⁴/kg). The mean biological half-life of ¹⁸⁶Relabeled cMAb U36 in blood was 72.6 ± 16.0 h, and bone marrow doses ranged from 2.1 to 2.8 Gy at the highest dose level. Myelotoxicity exceeding grade 3 was not observed. Stable disease was observed in five of nine patients, ranging from 3 to 5 months, and was still ongoing in one of these patients. Conclusions: This study indicates that a doubling of the maximum tolerated activity and bone marrow dose of ¹⁸⁶Relabeled cMAb U36 can be achieved using reinfusion of GCSF-stimulated unprocessed whole blood.