Atim-16. Mri-guided Convective Delivery of Mdna55, an Interleukin-4 Receptor Targeted Immunotherapy for the Treatment of Recurrent Glioblastoma
Year: 2017
Type: conference-abstract
Abstract: Intratumoral glioblastoma therapy has been limited by suboptimal spatial distribution of therapeutic agents. MR-guided convection-enhanced delivery (CED) of MDNA-55 (interleukin-4 fused to Pseudomonasexotoxin) is underway in a Phase 2 open-label study in up to 43 patients with recurrent glioblastoma. Gadolinium-based contrast agent (Gd-DTPA) is co-infused with MDN55 to optimize intra-tumoral catheter placement, monitor drug distribution and identify non-functional catheters. MR images acquired prior to, during, and following infusion are used to determine drug distribution, tissue response, and disease status. Depending on the tumor size up to 60 mL of MDNA55 at a concentration of 1.5 μg/mL is administered as a single infusion through each catheter for a maximum dose of 90 μg. We report preliminary results of tumor distribution in 6 subjects that underwent MR-guided delivery of MDNA55 via implantable flexible catheters. Target enhancing tumor volume varied between 1.5 to 24 mL and tumor diameter varied between 1.8 to 4.7cm. Volume of infusion ranged between 14 to 66 mL and was delivered via 1 to 3 catheters at a flow rate of up to 15mL/min per catheter. MR was employed to monitor initial infusion, allowing adjustment of catheter depth as needed. The bulk of the delivery was performed outside the MR scanner in awake patients. MR confirmation of the distribution was performed within 4 hours post-infusion. In all patients, remarkable tumoral and peri-tumoral distribution has been observed. Tumor coverage ranged from 43% to 100%. Ratio of volume of distribution (Vd) to the volume infusion (Vi) ranged from 2.2 to 0.6. Lower Vd/Vi ratios were associated with drug leakage into the CSF space and/or resection cavity. When catheter placement was inaccurate, real-time imaging of Gd-DTPA distribution enabled adjustments to catheter depth which dramatically improved tumor coverage. MR-guidance during CED is therefore critical for optimal drug distribution in brain tumors.
Source: Neuro-Oncology
Institutions: University of California, San Francisco, The University of Texas at San Antonio Health Science Center, The Ohio State University, Mays Cancer Center at UT Health San Antonio, The Ohio State University Wexner Medical Center, University of Alabama at Birmingham, Weill Cornell Medicine, Moffitt Cancer Center, Duke Medical Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767561583