Dr. Michaelis on Potential Combination Strategies With Ruxolitinib in Myelofibrosis

Laura C. Michaelis, MD, associate professor, Medical College of Wisconsin, discusses potential combination strategies with ruxolitinib (Jakafi) in myelofibrosis.

The JAK inhibitors ruxolitinib and fedratinib (Inrebic) are approved for the treatment of patients with myelofibrosis. Both agents have shown improved symptom burden and splenomegaly in patients with intermediate- or high-risk disease, says Michaelis.

However, some patients do not respond well to ruxolitinib, develop significant toxicities, or progress on the agent, explains Michaelis. As such, multiple combination strategies are being investigated to improve outcomes for these patients.

Ruxolitinib in combination with hypomethylating agents such as decitabine (Dacogen) or azacitidine (Vidaza) have been evaluated in patients who have newly diagnosed or accelerated phase disease, says Michaelis.

Agents such as interferon, danazol, or immunomodulatory agents like thalidomide (Thalomid), lenalidomide (Revlimid), pomalidomide (Pomalyst) could also lead to improved outcomes in combination with ruxolitinib, says Michaelis.

Finally, combining ruxolitinib with PI3K inhibitors, BET inhibitors, BCL-2 inhibitors, and NEDD8 inhibitors could lead to the development of important targeted approaches beyond the JAK/STAT pathway, concludes Michaelis.