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Expert Discusses Guidelines, Next Steps With MPNs

Chelsea LoCascio
Published: Monday, Dec 04, 2017

Brady L. Stein, MD
Brady L. Stein, MD
Updates to the NCCN guidelines on myeloproliferative neoplasms (MPNs) will drastically change how these diseases are managed, according to Brady L. Stein, MD.

“They were the only [malignancy] that had lacked representation from the NCCN, so we're really pleased that MPNs finally have guidelines,” said Stein. “That is the first and foremost important thing, is that we have practical management tips and these are, perhaps, largely based on consensus more so than evidence. [However], an evidence basis is starting to emerge for the management of these conditions.”

In an interview during the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies, Stein, an associate professor of medicine at Feinberg School of Medicine at Northwestern University, discussed the differences between the types of MPNs, the NCCN guideline changes, and the important role of JAK inhibitors.

OncLive: Can you share insight on the updates to the NCCN guidelines that include MPNs?

Stein: What is most important is that these somewhat rare entities finally have guidelines. They finally have some guidance for decision making in the setting of a relatively rare illness that had been previously unrepresented. I focused on the 3 classical MPNs: essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis.

In ET, there are a couple of important themes. First, with establishing a proper diagnosis, the differential diagnosis might include early myelofibrosis. We may not change management initially, but the long-term prognosis is very different between those 2 entities. It matters when we see young patients and we certainly see young patients who present with high platelet counts. [It] matters that we properly establish a diagnosis because this is meaningful in terms of the long-term expectations and prognosis.

The second part is learning how to use mutations in ET to guide management. There are 3 major mutations a patient with ET might have. The mutations certainly influence practical management; if a patient lacks a JAK2 mutation, they might not necessarily need aspirin. They might fit into a lower-risk category in terms of thrombosis risks, so they don’t always need cytoreductive therapies, such as hydroxyurea. There is a practical management that can come from knowing the mutation that your patient with ET has. In terms of novel therapies for ET, the clinical trial landscape is certainly more scarce compared with some of the other entities. We see less development in this area. There are certainly patients who need a second- or third-line therapy, but we don’t have many clinical trials yet to satisfy that patient population. There is certainly work to be done there.

The next is PV. What is different in the 2016 and 2017 range are the changing diagnostic criteria. The hemoglobin threshold has been lowered, so that we're not missing cases of PV. It’s important to make a proper diagnosis because there's a natural therapeutic [pattern] that will follow if we confirm the diagnosis of PV. Here we have guideline representation to help outline about the hematocrit target with phlebotomy, the use of aspirin, and which patients might be candidates for cytoreduction. It is so important. In terms of therapies for PV, hydroxyurea is widely used. It’s not necessarily used based on evidence; its use is based on experience and a lack of other good options.

There are other options that are currently being studied. One, of course, is pegylated interferon. There are important, randomized, phase III, high-quality studies comparing this class of medications to hydroxyurea. Having evidence to decide on first-line therapy is important for PV. Second-line therapies are well defined. With ruxolitinib (Jakafi)—there are data to use this as a second-line therapy in the small number of patients in whom hydroxyurea is inadequate. In terms of other agents, there are more agents in development for PV than there are certainly in ET and not as many in myelofibrosis. However, we are slowly changing to new developments and, hopefully, we will have approved drugs for the frontline setting. We already have an approved drug for the second-line setting.

Myelofibrosis…is the most challenging to manage because it is the rarest of the 3 [MPNs]. It’s 10 times less common than ET or PV in terms of its prevalence. It’s very hard to follow some of the nuanced management tactics. With treatment, we also have some guidance from NCCN. We have guidelines; they are in their second iteration and evolving. That is important.


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