Abstract 1605: Pretreatment of bone anabolic agent delays or prevents multiple myeloma progression
Authors: Syed Hassan Mehdi, Dongjoon Lee, Alex Lee, Paul Lee, Donghoon Yoon
Journal: Cancer Research (2025)

Abstract Multiple myeloma (MM) is the second most common blood cancer. It remains an incurable disease due to relapsing and developing treatment resistance. Treatment resistance and disease progression are not solely due to intrinsic MM characteristics but are also fostered by alterations within the surrounding BM microenvironment. The bone serves as a home for growing myeloma but is also a target organ for myeloma cells. The MM-bone disease (MMBD) is one of the defining features of MM. A previous report showed that myeloma cells colonize the endosteal niche, enter a dormant state, and are activated by bone-lining cells. Many attempts, including ours, were made to test novel or existing bone anabolic drugs for anti-MMBD and found they did not significantly affect myeloma progression, although bone formation has improved. Interestingly, we found that the surviving mice from myeloma transplants become tolerable to subsequent tumor transplantation. We hypothesized that improving the bone environment may lead to the prevention of myeloma growth. We pretreated mice with a bone anabolic agent, Sigma Ant-Bonding Calcium Carbonate (SAC), and then tested myeloma growth. It may mimic a treatment in the pre-emerging or -relapsed period of MM. SAC is a chemically/physically modified calcium carbonate with a unique weak bonding and a commercially available dietary supplement. It induces bone formation by increasing the active ionized calcium in the body. We divided the 8-12-week-old NOD SCID gamma mice into three groups: PBS, the SAC-Treated group before Transplant (TbT), and the SAC-Treated group after Transplant (TaT). SAC was gavaged twice daily, five days/week, for four weeks before the transplantation (TbT) or two weeks after transplant (TaT), while PBS was gavaged to the control group when TbT started. The 1x106 luciferase-expressing 5TGM1 cells were injected into the mice via the tail vein. Mice were imaged weekly by IVIS imager to assess the myeloma progression and terminated when endpoint criteria were met. All surviving mice were sacrificed one week after all PBS group mice died. We found that the median survival of PBS-treated mice was 39 days, while 45 days in the TaT group. To our surprise, 80% of TbT group mice survived until the end of the study. The bioluminescence image analysis showed that myeloma slowly progressed in both treated group mice. DEXA results demonstrated that bone minerals significantly increased in the spine of SAC-treated mice compared to the control mice. Trabecular thickness and bone volume density were significantly higher in the SAC-treated group at the lumbar spine compared to the PBS group. In conclusion, our results showed that improving the bone microenvironment with SAC pretreatment delays or prevents myeloma cell growth in mice. These results may suggest a novel therapeutic regimen for MM during pre-emerging or -remission of multiple myeloma patients. Citation Format: Syed Hassan Mehdi, Dongjoon Lee, Alex Lee, Paul Lee, Donghoon Yoon. Pretreatment of bone anabolic agent delays or prevents multiple myeloma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1605.