INCB052793, a selective JAK1 inhibitor, alone and in combination in vitro and in vivo in patients with multiple myeloma

Previous studies have shown constitutive activation of the JAK-STAT pathway in multiple myeloma (MM) through dysregulated signaling of cytokines such as IL-6. Eric Sanchez from the Institute for Myeloma & Bone Cancer Research, West Hollywood, USA, and colleagues conducted a study to assess the selective JAK1 inhibitor INCB052793 (INCB) alone and in combination with anti-MM agents in vitro and in vivo. The results were published ahead of print in Annals of Hematology.

Materials and methods

• INCB052793: three doses at 3, 10, and 30 mg/kg
• MM xenograft models
• MM cell lines and primary MM cells: RPMI8226 and U266

Key findings

• Significant inhibition of cell viability of primary MM cells was seen with single-agent INCB
• Inhibition of primary MM was enhanced with singleagent INCB in combination with other anti-MM agents including proteasome inhibitors and glucocorticosteroids
• Single-agent INCB reduced tumor growth of the MM xenograft LAGκ-1A growing in severe combined immunodeficient mice
• Mice receiving INCB at a dose of 30 mg/kg showed a significant reduction in tumor volume on days 28, 35, 42, 49, 56, and 63
• INCB at a dose of 10 mg/kg resulted in significant anti-tumor effects on days 56 and 63
• Tumor-bearing mice receiving combinations of INCB with carfilzomib, bortezomib, dexamethasone, or lenalidomide had significantly reduced tumors in comparison with vehicle control and mice treated with single agents

The authors concluded by stating that “since MM patients will inevitably develop resistance to their therapies, new treatment regimens are needed to prolong their survival. These results provide further support for the clinical evaluation of INCB052793 alone and in combination treatment for MM patients.”