Abstract
Background: Multiple myeloma remains an incurable disease. Treatment with immunomodulators and proteasome inhibitors have provided significant benefits to patients but they still relapse. The introduction of new treatments like daratumumab have provided further benefit. However, patients continue to experience issues and relapse. CLR 131 is a novel radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells to provide targeted delivery of iodine-131 directly to tumor cells. This study evaluates the effect of fractionated injections of CLR 131 in OPM-2 tumor bearing mice in comparison to equivalent doses of CLR 131 and the standard dosing of bortezomid.
Methods: The OPM-2 cell line (human multiple myeloma) was purchased from American Type Culture Collection (ATCC, Rockville, MD) and maintained in McCoy's 5a media supplemented with 10% fetal bovine serum. Female CB17 SCID mice approximately 5-7 weeks of age were injected subcutaneously with 1x107 viable cells (in ~100 µL Dulbecco's PBS) into the right flank. The study was initiated when tumor size had reached a pre-determined size (approximately 150-200 mm3). The mice were given potassium iodide at a concentration of 0.1% in their drinking water to block possible free iodide in the drug formulation three days prior to injection and continuing through two weeks post-injection.
Results: All treatment groups showed a reduction in tumor growth with the fractionated dose of CLR 131 producing the greatest inhibition. The control group showed exponential growth throughout the study, increasing in volume by an average 11 fold from baseline. This compared with a 3.5 fold increase from baseline in the fractionated dose group and 7.5 fold for the bortezomid group.
Conclusions: The results of the study indicated that a fractioned injection of CLR 131 (2 injections of ~50 µCi) on human multiple myeloma (OPM-2) tumor bearing model showed a significant inhibition of tumor growth as well as a survival benefit. While a single injection of CLR 131 at either ~50 uCi and ~100 uCi were effective, there was an important improvement with by using fractionated dosing. The implication is that in this clinically predictive in vivo model CLR 131, which is currently in a Phase 2 clinical trial for multiple myeloma, might show improved clinical efficacy in patients if a fractionated dose is utilized.
Citation Format: Jarrod Longcor, Maria Banach, John Friend. Efficacy of fractionated injections of CLR 131 in a OPM-2 SCID nude mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-279.
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