Dr Rampal on the Benefits and Limitations of JAK Inhibitors in Myelofibrosis

“Myelofibrosis is not a monolithic disease, and the selection of treatment needs to be tailored to what the underlying issues and challenges the patient is facing.”

Raajit Rampal, MD, director of the Center for Hematologic Malignancies and director of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discussed considerations for ongoing treatment decision-making in myelofibrosis.

Myelofibrosis is a heterogeneous disease, and treatment selection must be individualized based on patients’ specific pathophysiology and clinical challenges, Rampal began. First and foremost, therapy should be aligned with the predominant driver of disease burden, he said. Secondly, although it is essential to understand the clinical benefits of the available JAK inhibitors, oncologists must also recognize the limitations of these agents and monitor for warning signs of treatment failure, he emphasized. Moreover, spleen volume reduction has been correlated with survival, underscoring the importance of serial spleen measurements during therapy, he noted. Patients who exhibit concerning trends—such as splenomegaly progression or lack of spleen size reduction—should be considered for alternative therapies or enrollment in clinical trials, he reported. These clinical indicators are critical for guiding ongoing management decisions, Rampal stated.

The most recent JAK inhibitors to enter the myelofibrosis treatment paradigm are pacritinib and momelotinib. In 2022, pacritinib received accelerated approval from the FDA for the treatment of adult patients with intermediate- or high-risk primary or secondary myelofibrosis with a platelet count below 50 × 109/L. In the pivotal phase 3 PERSIST-2 trial (NCT02055781), patients who had a baseline platelet count below 50 × 109/L achieved an SVR35 rate of 29% in the pacritinib arm vs 3% in the placebo arm.

In 2023, momelotinib received FDA approval for the treatment of adult patients with intermediate- or high-risk primary or secondary myelofibrosis with anemia. In the pivotal phase 3 MOMENTUM trial (NCT04173494), a Myelofibrosis Symptom Assessment Form v4.0 total symptom score reduction of at least 50% was observed in 25% of patients who received momelotinib (n = 130) vs 9% of those who received danazol (n = 65; P < .01).