Dr Jain on the Role of Ruxolitinib in Polycythemia Vera and Myelofibrosis

“For polycythemia vera, the only JAK inhibitor that is approved right now is ruxolitinib, and it is approved for second-line therapy. This is for patients who are hydroxyurea-intolerant or hydroxyurea-resistant—there is a potential benefit with ruxolitinib.”

Akriti G. Jain, MD, a hematologist and medical oncologist at the Cleveland Clinic, discussed the role of ruxolitinib (Jakafi) for the treatment of patients with polycythemia vera and myelofibrosis.

In December 2014, the FDA approved ruxolitinib for the treatment of patients with polycythemia vera who are resistant or intolerant to hydroxyurea. Ruxolitinib continues to stand as the only FDA-approved JAK inhibitor for the treatment of patients with polycythemia vera, with the agent indicated in the second-line setting, Jain began. She noted that this patient population could derive potential benefit from ruxolitinib, especially with a reduction of JAK2 allele burden, which could potentially be disease modifying.

Furthermore, the FDA approved ruxolitinib in November 2011 for the treatment of patients with myelofibrosis. Although JAK inhibitors have demonstrated their importance regarding symptom control and spleen volume control in myelofibrosis, disease modification is more difficult to confirm, Jain added. There have not been many observations of fibrosis reversals, which is being evaluated in combination trials to further identify room for improvement in the work of JAK inhibitors to potentially be disease modifying, she asserted. So far, within the myelofibrosis treatment paradigm, ruxolitinib has been the only JAK inhibitor that has demonstrated survival benefit, although fibrosis benefit and disease modification remain an unmet need, according to Jain.

The myelofibrosis treatment paradigm has seen a significant shift within the past decade, considering the addition of 3 JAK inhibitors. In 2019, the FDA approved fedratiib (Inrebic) for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis after polycythemia vera or essential thrombocythemia. Moreover, in 2022, the FDA approved pacritinib (Vonjo) for the treatment of adult patients with intermediate or high-risk primary or secondary myelofibrosis with a platelet count less than 50 x 109/L. Most recently, in 2023, momelotinib (Ojjaara) received the green light from the FDA for the treatment of patients with intermediate or high-risk myelofibrosis, including primary or secondary myelofibrosis with anemia.