Emerging Agents, Treatment Selection Criteria Key to Improving Outcomes in Myelofibrosis

Neil Dunavin, MD, MS

Choosing the optimal treatment for patients with myelofibrosis remains a challenge in clinical practice, explained Neil Dunavin, MD, MS. However, factors can be taken into consideration that can help with making that decision, he said.

"[I focus] on 3 main points to determine what the right treatment for my patient is," explained Dunavin. "The first is to get an accurate assessment of the patient's risk or prognosis. The second is to get an accurate assessment of their symptom burden. The third is to determine whether the patient is eligible for an allogeneic stem cell transplant (allo-SCT). Knowing those [criteria] can help you come up with a treatment plan."

One treatment method is JAK1/2 inhibition. In 2011, the JAK1/2 inhibitor ruxolitinib (Jakafi) became the first agent approved by the FDA to treat patients with myelofibrosis. A second method is fedratinib (Inrebic): In August 2019, the FDA approved the JAK2 inhibitor for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post—polycythemia vera or post–essential thrombocytopenia) myelofibrosis.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Hematologic Malignancies, Dunavin, a clinical hematologist and assistant professor of medicine at the University of California, San Francisco School of Medicine, highlighted criteria to consider when approaching treatment selection for patients with myelofibrosis and discussed next steps for the field.

OncLive: How would you define the current treatment paradigm of myelofibrosis?

Dunavin: Myelofibrosis is associated with many symptoms, due to the cytokines released by the disease. Patients may have low blood counts that require transfusion, [and they may also experience] fatigue, sweats, and enlarged spleens.

Currently, ruxolitinib is the first-line treatment for patients who have adequate blood counts and symptoms of myelofibrosis. Ruxolitinib is an oral medication taken twice daily that may control disease symptoms.

Could you expand on the 3 main criteria you use to guide treatment selection?

[The first step] is to assign a disease risk score. As far as prognosis goes, multiple scoring systems have been developed over the last 5 years. With these systems, you can use clinical and laboratory information to assign a patient to a risk category. That category [allows you] to estimate what outcome the patient will have. Some myelofibrosis cases progress slowly and require little therapy, while others progress rapidly and should be treated more aggressively up front.

[The second step] is to assess symptom burden. The goal of treatment in myelofibrosis is to alleviate [symptoms]. Using available tools, we can completely classify the symptoms the patient is having to determine if the treatment we are using is efficacious or should be switched.

Finally, [the third step] is to determine whether or not the patient is a transplant candidate. The only [way we can effectively get rid of myelofibrosis] is to do an allo-SCT from a donor.

Allo-SCT is a risky therapy with some toxicities; however, in the right patient, at the right time, allo-SCT can [effectively get rid of] myelofibrosis. A substantial number of patients do very well with transplant, but it is too risky for others. Factors, such as age and comorbidities, [are important considerations].

Should any exciting data from the 2019 ASH Annual Meeting be highlighted?

I was excited to see novel therapies [being combined] with ruxolitinib. I hope [these combinations] move on to later-phase studies. I did not, however, see a large, practice-changing phase III study.

Luspatercept-aamt (Reblozyl) is an interesting, red-blood-cell—stimulatory agent. It is approved for patients with beta thalassemia. Additionally, it may be approved for patients with myelodysplastic syndrome with ring sideroblasts who need more red blood cells. Going forward, it would be interesting to see if it can be used in myelofibrosis, too.