RXR modulators to improve the efficacy of immunomodulatory agents in multiple myeloma treatment

Unmet Need

Multiple myeloma (MM) is the second most common hematological malignancy in the United States. Although current anti-myeloma therapeutics help patients live with the disease for more than 10 years, MM remains an incurable disease with high rates of drug resistance and relapse. The global MM therapeutic market is estimated to be $22.9 billion in 2023 with a CAGR of 10.4%. In the United States, there are 5–7 new cases of MM per 100,000 individuals yearly, primarily observed in the elderly population who often have co-existing medical problems. Approximately 26% of MM patients have diabetes and 29.3% have dyslipidemia. There is a need for the development of novel anti-myeloma treatments with low drug resistance, especially for patients with co-existing diabetes and/or dyslipidemia.

Technology

Duke inventors have developed a method to improve multiple myeloma (MM) immunomodulatory treatment. This is intended to be used in MM patients with co-existing diabetes and/or dyslipidemia. Specifically, the treatment method consists of a RXR (retinoid X receptor) modulator and an immunomodulatory agent. This has been demonstrated by investigating the effects of RXR modulators on the anti-myeloma activity of immunomodulatory agents as well as the level of glucose and lipids. The inventors found that RXR heterodimer agonists enhanced myeloma cells’ sensitivity to immunomodulatory agents through in vitro cell studies and in vivo myeloma mouse models. They showed that administration of RXR agonists, such as LG100754, could be an effective strategy to overcome drug resistance in the treatment of MM, while providing additional benefits for patients with comorbidities, such as diabetes and/or dyslipidemia. The results provide a strong justification for future clinical trials to test the efficacy of RXR agonists in combination with immunomodulatory agents in MM patients.

Other Applications

This technology could also be used for patients with other types of blood cancers, such as lymphoma and myelodysplastic syndrome, who are treated with immunomodulatory agents.

Advantages

• A novel approach for enhancing the efficacy of immunomodulatory agents using RXR modulators to treat blood cancers such as multiple myeloma
• Provides the first evidence that RXR heterodimer agonists are promising small-molecule drugs that can enhance the sensitivity of myeloma cells to immunomodulatory agents
• Enables both anti-myeloma and glucose/lipid-level lowering effects