Dr Gerds on How to Approach JAK Inhibitor Selection in Myelofibrosis

Many people will go through their minds and say, ‘Let's think about if ruxolitinib is a good idea,’ and if the answer is yes, we use it. If the answer is no, then we think about the other JAK inhibitors.

Aaron Gerds, MD, MS, a physician in the Department of Hematology and Medical Oncology at Cleveland Clinic, as well as an assistant professor in the Department of Medicine of the School of Medicine, deputy associate director for Clinical Research, and a member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center at Case Western Reserve University, discussed his approach to selecting among the 4 FDA-approved JAK inhibitors—ruxolitinib (Jakafi), fedratinib (Inrebic), pacritinib (Vonjo), and momelotinib (Ojjaara)—for patients with myelofibrosis.

Gerds began by pointing how ruxolitinib remains the reflexive first choice in clinic after it was the first JAK inhibitor approved in this setting. When determining a treatment plan, clinicians often run through whether ruxolitinib is a good choice, and if the answer is yes, they use it; if the answer is no, they weigh the other agents, he said.

Gerds framed the remaining decision around blood counts. For a patient with proliferative myelofibrosis, defined as a good platelet count and no significant anemia, ruxolitinib is right choice, he noted. When a patient has anemia, Gerds often turns to momelotinib for those who need spleen and symptom control alongside myelofibrosis-associated anemia.

Pacritinib is the agent Gerds considers for patients with platelet counts below 50 × 10⁹/L, which reflects the FDA prescribing information, or for those whose platelets could soon fall to that level, he added. He noted that patients with platelet counts as high as 100 × 10⁹/L were enrolled in the phase 3 PERSIST-2 trial (NCT02055781), which supported its FDA approval.

Fedratinib, Gerds concluded, is where he lands for patients who have received prior ruxolitinib. In the phase 2 JAKARTA2 trial (NCT01523171), the agent produced high rates of spleen volume and symptom response among patients previously treated with ruxolitinib, he explained.