Dr. Garcia on the Role of Ruxolitinib in Myelofibrosis

Jacqueline S. Garcia, MD, physician, Dana-Farber Cancer Institute, assistant professor of Medicine, Harvard Medical School, discusses the role of ruxolitinib (Jakafi) in myelofibrosis.

After ruxolitinib was approved by the FDA in 2011 for the treatment of myelofibrosis based on splenic volume reduction compared with placebo and best available therapy in the phase 3 COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) trials, respectively, the agent became the standard of care for patients with symptomatic advanced myelofibrosis, Garcia says. Long-term follow-up also demonstrated that ruxolitinib produced an overall survival benefit compared with placebo and best available therapy, Garcia adds.

However, many patients treated with ruxolitinib may develop resistance, have suboptimal responses, or experience relapse or progression, creating a need for additional therapies, Garcia explains. In August 2019, the FDA approved the JAK inhibitor fedratinib (Inrebic) for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. In February 2022, the FDA has granted an accelerated approval to pacritinib (Vonjo) for the treatment of adult patients with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.

At the dose of ruxolitinib typically given to patients with a platelet count below 50 × 109/L, the agent is not as active, Garcia continues. Findings from the phase 3 PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials showed that pacritinib was effective in this subset of patients, and additional findings from PERSIST-2 are still anticipated, Garcia concludes.