Pacritinib Bests Available Therapies for Myelofibrosis

A new JAK2 inhibitor, pacritinib (CTI Biopharma), outperformed best-available therapy for patients with myelofibrosis in a phase III trial, an encouraging development particularly for those with low blood platelet counts.

Treatments are few for patients with myelofibrosis, a rare blood cancer that develops when the bone marrow doesn't make enough normal blood cells. To compensate, the spleen takes over blood cell production, causing it to enlarge. Patients also experience tiredness, weakness, shortness of breath, fever, and weight loss; in one third, myelofibrosis transforms into acute leukemia.

The only cure for myelofibrosis is an allogeneic hematopoietic stem cell transplant, which is not an option for many. The only FDA-approved treatment is the JAK inhibitor ruxolitinib (Jakafi; Incyte), but it cannot be given to patients with low platelet counts. About 25% of myelofibrosis patients have low platelet counts (<50,000/μL) at diagnosis; others experience low platelet counts as a result of their therapy. Patients not taking ruxolitinib turn to an assortment of “best-available therapies,” drugs that are prescribed off-label, such as erythropoietin-stimulating agents; immunomodulatory drugs, namely thalidomide and lenalidomide; and hydroxyurea. Many patients have anemia and are dependent on regular blood transfusions.

In the new trial, dubbed PERSIST-1, researchers randomly assigned 327 patients to treatment with pacritinib or best-available therapy. After 24 weeks, 19.1% of patients on the pacritinib arm experienced spleen shrinkage, defined as a reduction in volume of at least 35%, compared with only 4.7% of patients on the control arm, said Ruben A. Mesa, MD, deputy director of the Mayo Clinic Cancer Center in Scottsdale, AZ. He presented the findings at the American Society of Clinical Oncology Annual Meeting, held in Chicago, IL, May 29–June 2.

In the subgroup of patients with the lowest platelet counts—those ineligible for ruxolitinib—spleen shrinkage occurred in 33.3% of patients in the pacritinib arm and 0% in the control arm, reported Mesa. These patients also experienced a 35% increase, on average, in platelet counts.

In addition, those taking pacritinib experienced greater relief from symptoms such as weight loss, night sweats, fever, and bone pain. The drug also helped to alleviate anemia in some patients: Among those who had been dependent on blood transfusions, 25.7% no longer needed them. In contrast, none of the patients receiving best-available therapy were able to forgo transfusions, Mesa said.

Given the effectiveness of pacritinib, 79% of patients receiving best-available therapy crossed over to the pacritinib arm.

Mesa said that longer follow-up is needed to determine whether pacritinib prolongs survival. The ongoing phase III PERSIST-2 trial is exploring pacritinib for the treatment of patients who have low blood platelet counts due to their disease or their therapy.

Furthermore, “based on preliminary data, pacritinib may be disease modifying and warrants combination studies with other potentially disease-modifying agents in myeloproliferative neoplasms,” remarked Mesa.