Dr Jain on Considerations for Sequencing JAK Inhibitors in Myelofibrosis

“The sequencing of JAK inhibitors doesn't have a lot of clinical trial [data]; therefore, we do not have a lot of clinical trials to help us figure out how to sequence JAK inhibitors. We usually pick one based on the presentation of whether anemia is a problem or [if] thrombocytopenia is a problem, [along with other factors].”

Akriti G. Jain, MD, a hematologist and medical oncologist at the Cleveland Clinic, discussed sequencing strategies with JAK inhibitors and novel combination therapies for the treatment of patients with myelofibrosis.

Sequencing strategies are still not officially established in myelofibrosis, with a lack of prospective clinical trial data to help guide these decisions, Jain began. When sequencing in clinical practice, treatment selection is often based on the presentation of whether problems arise regarding anemia or thrombocytopenia, or based on a patient’s blood counts, she explained. Typically, when a patient has good blood counts, the first option is the JAK inhibitor ruxolitinib (Jakafi), she added. However, she noted that dose modifications may be necessary based on cytopenias and adverse effects. Having a window of between 12 to 24 weeks to achieve a response is optimal, which reflects end points often used in clinical trials, she asserted. Nevertheless, if a response has not been achieved by 12 weeks, then moving onto the next treatment is key, she stated. Following the first treatment, observing problems regarding anemia and thrombocytopenia remains essential, she said.

Within the myelofibrosis space, 3 other JAK inhibitors have also been approved by the FDA. 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. 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. In 2023, momelotinib (Ojjaara) received FDA approval for the treatment of patients with intermediate or high-risk myelofibrosis, including primary or secondary myelofibrosis with anemia.