Optimizing Clinical Decision Strategies for Ruxolitinib in Myelofibrosis

Ruxolitinib has been used as a therapy for myelofibrosis for approximately 15 years, as of 2025. According to Francesca Palandri, MD, PhD, it has demonstrated superiority over other best available therapies for toxicities. The response rates, however, remain inconsistent, with a wide range of patients failing on and discontinuing ruxolitinib 3 to 5 years after treatment initiation.

Palandri, an adjunct professor in the Department of Medical and Surgical Sciences at the University of Bologna in Bologna, Italy, spoke with CancerNetwork® at the Society of Hematologic Oncology 2025 Annual Meetingabout her presentation on predictive biomarkers for ruxolitinib as a myelofibrosis therapy.

Specifically, she noted that patients with a high percentage of blasts and those who have a cytopenic phenotype will receive less benefit from treatment with ruxolitinib compared with others. There is also a need for the timelier use of ruxolitinib due to its potential prognostic implications.

Palandri added that there may also be a use for molecular data in deciding whether ruxolitinib should be used in patients with RAS mutations.

Transcript:

We have been using ruxolitinib for nearly 15 years now, and this has proven clear superiority vs the [best available therapy], for example, hydroxyurea and corticosteroids in the control of splenomegaly symptoms. Still, the response rates vary [significantly], and we have 40% to 70% of the patients who, finally, will fail ruxolitinib and discontinue the drug in 3 to 5 years. That’s why it is so important to assess predictors of response to orient our clinical decision strategy.

Looking at predictors of response, both in terms of clinical and molecular evaluation, they affect our clinical practice because we can select the best frontline JAK inhibitors for the treatment. For example, for a patient with a high percentage of blasts, ruxolitinib therapy may not be optimal. Also, for patients who have a cytopenic phenotype, ruxolitinib may not be the go-to option. On the other hand, we must learn how to deal with ruxolitinib dosing and how to be timely in our treatment decision to start ruxolitinib because this may have a prognostic implication. Also, the use of molecular data may orient not only the decision for transplantation, but perhaps also help to avoid ruxolitinib for patients with RAS/CBL mutations.