Myelofibrosis disrupts the body’s normal production of blood cells. This can cause scarring in the bone marrow that leads to anemia, which can worsen over time. Hepcidin is a hormone produced in the liver that acts as an iron regulator which can cause anemia and chronic inflammation due to elevated levels in patients with myelofibrosis. 

A New Study

An abstract presented by Dr. Sanjay Mohan from Vanderbilt-Ingram Cancer Center at the 2023 American Society of Hematology conference discussed results from a Phase 1/2 study looking at the use of a medication called zilurgisertib administered both by itself and in combination with ruxolitinib in patients with anemia due to myelofibrosis. Zilurgisertib is an activin receptor-like kinase-2 inhibitor. “Activin receptor-like kinase-2 (ALK-2) contributes to myelofibrosis-associated anemia via hepcidin upregulation.” This study is currently ongoing and recruiting.

Criteria to Participate in the Study

• Patients must be 18 years or older. (Median age is currently 73)
• Patients must have intermediate or high-risk with primary or secondary myelofibrosis
• Patients must have anemia whether they are transfusion or non-transfusion dependent

The Study Specifics

Group 1: The study started patients at 50mg of zilurgisertib and increased dosage until the maximum tolerated dose was reached.

Group 2: The second group of the study started patients on ruxolitinib for the first 12 weeks, then introduced zilurgisertib at 100mg.

The Study Results

“Treatment with zilurgisertib monotherapy or in combination with ruxolitinib in this patient population was generally well tolerated,”

• 55% of Group 1 and 25% of Group 2 were transfusion-dependent when starting the study
• Hepcidin was high in both groups to begin with
• Thrombocytopenia (low platelet levels) was the most common side effect found among participants 
• The higher doses of both medications lowered the anemia risk in patients

Conclusion

Anemia can be a serious condition for myelofibrosis patients. Fatigue, weakness, shortness of breath and dizziness can result from myelofibrosis and its effect on the bone marrow. This ongoing study has shown that, “reduced hepcidin levels were observed at all dose levels with both monotherapy and in combination with ruxolitinib, with greater control of hepcidin over time observed at higher zilurgisertib doses. Preliminary improvements in anemia were observed in non–transfusion-dependent patients during dose escalation, suggesting potential for therapeutic activity.”