Landscape for Myeloproliferative Disorders Becoming More Defined With Improved Treatments, Biomarkers

Elizabeth Leick and Gina Columbus
Published Online: Wednesday, Jan 11, 2017

The most important breaking story is likely cardiovascular or vascular risk. Patients need to have a good base on cardiovascular assessment, like they should have in primary care—or maybe at the direction of the oncologist to see a specialist to know what their comorbidity really is. They need to manage that as they navigate through TKI therapy, as well as drugs with vascular risk.

What is important to highlight regarding myeloproliferative neoplasms (MPNs)?

Here, we are a little further behind CML. However, we are really making nice progress. One important thing in 2016 was the update of the World Health Organization's (WHO) definitions of MPNs. What used to be called masked polycythemia vera (mPV) is now identified, which means we've lowered the bar and recognized patients with PV. Patients who have lower but still elevated hemoglobin levels may have PV and should be evaluated and diagnosed as such.

We've recognized a prefibrotic form of myelofibrosis, which was always tough to separate from thrombocytosis or overt myelofibrosis. It's now a category in WHO. We've received some nice clarification of what were the trickier forms of MPNs to diagnose.

We've also seen the first appearance of guidelines for MPNs from the NCCN. We don't have the full set of treatment guidelines. What we have now for myelofibrosis is some direction on how to treat our patients based on their risk. There was an important notification that patients should have their symptoms assessed by a symptom-assessment scale—a tool that's been validated and published. We shouldn't forget about autologous transplant with such patients.

When we think about therapeutics, there have been some big questions in the field and thinking about PV and thrombocytosis for ET. There is a large trial that has accrued and is asking this question for high-risk patients without previous therapy: is interferon versus hydroxyurea—which tends to be the standard—more effective? What's the real benefit? It’s too early to say.

At the 2016 ASH Annual Meeting, through the MPN consortium, we saw a presentation of this important study that is showing pretty equal results with regards to hematologic response, bone marrow, and molecular response. The thinking is that you will probably need to wait a little longer to see that data mature to fully assess it.

Also at the meeting, with regard to myelofibrosis, we've had ruxolitinib (Jakafi) approved for many years and have been looking for competition. Can there be a different JAK inhibitor that could offset some of the anemia we see with ruxolitinib? What about patients with low platelets? They're hard to treat. There are updated data from studies of pacritinib, which is a JAK inhibitor, with the possibility to be useful in patients with low platelets.

Not presented at ASH, but in the background, is updated data on momelotinib, another JAK inhibitor with a probable ability to offset anemia. Some of its trials showed that it could hold its ground and offer some of the similar benefits of ruxolitinib, but not as complete as we thought. We are soon going to have alternative JAK inhibitors that allow us to treat patients with more difficult blood count imbalances.

Who are the most appropriate patients to receive ruxolitinib?

It's important to identify the patient that can benefit from JAK inhibitor therapy. It's going to be the patient with symptoms and high-risk disease. The main benefits of ruxolitinib are going to be spleen size reduction and symptom management. These patients, by default, are often some of the higher-risk patients, particularly with enlarged spleens. It's remarkable to see the symptom control and the improvement in quality of life. Even the improvement in survival is probably due to global reduction of complications such as thrombosis and comorbid complications from the burden of advanced myelofibrosis.

Can you speak to ruxolitinib’s role in PV?

Ruxolitinib has been approved for PV for a while now. It probably stands on the middle ground as the drug we would think of after some initial therapy—whether or not it's hydroxyurea. I mentioned that interferon and hydroxyurea are battling for first place in the higher-risk PV patient. Ruxolitinib offers the ability to render someone's phlebotomy independent and show spleen size reduction and good symptom improvement, similar to how we see it in myelofibrosis. It's an improved drug for the patient who doesn't respond to hydroxyurea.




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