Educated Patient® MPN Summit Future Treatment of Polycythemia Vera Presentation: November 19, 2022

The current landscape of treatment for polycythemia vera is to reduce the risk of blood clotting and control blood counts. However, future treatments will need to go beyond that and target MPN stem cells to potentially change the course of the disease, according to an expert.

Dr. John Mascarenhas, a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, discussed the future of treatments for patients with polycythemia vera further at CURE®’s Educated Patient® MPN Summit.

Patients with polycythemia vera are at risk of thrombosis or blood clots that block the veins or arteries. To do this, therapies control blood counts with attention to the hematocrit. This is a measure how many red blood cells are in the blood and is normally between 38.3% and 48.6% for men and 35.5% to 44.9% for women.

“I think what patients want to hear, I think is what we’re interested in in the research community is going above and beyond that,” he said in an interview with CURE®.

Currently there are a few drugs that are affective in lowering blood counts, such as hydroxyurea, Jakafi (ruxolitinib), interferon alfa-2a and interferon alfa-2b. And although these are good treatments, Mascarenhas explained, there is still more to be done in future treatments.

“I think (what’s) really important to convey to patients is (that) our goals as a research community should really be elevated now beyond count control and thrombosis reduction — which are not unimportant,” he said. “But really what we need to do is figure out is how we address the disease at its core, so that we are not just reducing thrombosis risk by changing the disease process, but by remitting the disease, by changing the disease trajectory so that it’s less likely patients with develop progressive disease, myelofibrosis or acute myeloid leukemia. And then we can start talking about cure and functional cure, because that’s not something we do in (polycythemia vera) quite yet.”

To do this, future treatments for polycythemia vera will need to target to the MPN stem cell in the bone marrow to potentially change the course and behavior of the disease, he explained.

A good example of this is Besremi (ropeginterferon a-2b-njft), which was approved in November of 2021. It has been effective in controlling blood counts and reducing the risk of thrombosis and some patients are having “very deep” responses in driver mutation levels — which suggests that it may change the disease process, Mascarenhas noted.

Another drug of interest, which is currently in phase 3 clinical trials, that he highlighted is Rusfertide (PTG-300). This is a protein that is secreted by the liver as an inflammatory protein that then affects iron metabolism and distribution — which in polycythemia vera is very low. What it would do is, through an injection, turn off the channels that absorb iron and then distribute iron to red blood cells in the bone marrow. There is “compelling data” demonstrating phlebotomy (a procedure in which a needle is used to take blood from a vein, usually for laboratory testing) freedom with a weekly injection for some patients, he added.

“It doesn’t exactly fit the bill, in my opinion, for an anti-stem cell therapy,” Mascarenhas said. “But it could be a drug in certain patients, if they’re having excessive phlebotomy needs and challenges controlling that with their current therapies, that could be added on to better control their hematocrit.”

Other drugs that are still early in development but are of interest in changing the course of the disease include an LSD1 inhibitor, bomedemstate, and an HDAC inhibitor, givinostat.

“So there are other drug mechanisms that have potential to affect the behavior of these (polycythemia vera) stem cells that may change their interactions with cells in the bone marrow and the spleen, and may potentially change the course of the disease,” he added.

Mascarenhas noted that it is important for patients with polycythemia vera to stay educated on future treatments so that they can have better conversations with their physician about their treatment trajectory.

“There has to be a matching of goals and expectations, both on the patient side and the physician side,” he concluded. “I think that dialogue is really important because patients need to understand what the goals of treatment are when a physician prescribes a medication, the limitations and set that expectation.”

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