Yelena Ginzburg, MD

Yelena Ginzburg, MD, associate professor of medicine, hematology, and medical oncology at Mount Sinai, discusses a long-term goal of the use of rusfertide (PTG-300) in patients with chronic polycythemia vera.

Polycythemia vera is one of several types of myeloproliferative neoplasms; it is often treated with therapeutic phlebotomy. In the phase 2 PTG-300-08 trial (NCT04767802), patients received rusfertide to evaluate whether twice-weekly treatment followed by weekly maintenance doses could maintain hematocrit levels below 45% without phlebotomy. 

Results presented at the 2021 American Society of Hematology annual meeting

 showed that all 16 patients who received rusfertide had reduced and maintained lower hematocrit levels.

According to Ginzburg, a long-term goal of the use of rusfertide is a prolonged reduction of the need for phlebotomy, which could also lead to a reduced risk of thrombosis. Though this was not an end point for this study, further research with rusfertide could confirm that patients with polycythemia vera have fewer phlebotomy procedures in the long term and fewer thrombotic events.

The phase 3 VERIFY study (NCT05210790) will evaluate the efficacy of rusfertide versus placebo in a larger patient population and include the mean number of phlebotomies required by patients as a secondary end point.

 I think the main point that we are hoping to see with the trial as it continues is both a prolonged, continuous either phlebotomy-free or phlebotomy-reducing effect of using rusfertide in the chronic setting that can also ultimately allow us to evaluate a potential reduction in the thrombotic events in this patient population. So, if the patients who require high levels of phlebotomy have a higher risk of thrombosis in this PV population, then reducing the need for therapeutic phlebotomy may uncover a significant reduction in the risk of thrombotic events in this patient population. Although that requires a longer time for evaluating and it is not really an end point that is required, we are hopeful that—not in this trial—but the use of this agent will eventually increase that additional benefit for this patient population.

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Yelena Ginzburg, MD, discusses a long-term goal of the use of rusfertide in patients with chronic polycythemia vera. 

Rusfertide May Reduce Need for Therapeutic Phlebotomy in Polycythemia Vera

Yelena Ginzburg, MD, associate professor of medicine, hematology, and medical oncology at Mount Sinai, discusses the prognosis and standard-of-care treatment in patients diagnosed with polycythemia vera.

Polycythemia vera is one of several types of myeloproliferative neoplasms. It is often associated with long-term survival up to 20 years. Lower-risk patients tend to be younger and have less risk of thromboembolic events, which have a high mortality risk, while high-risk patients tend to be older and may have a history of thromboembolic events.

Therapeutic phlebotomy is often the primary treatment for polycythemia vera, especially for patients with low-risk disease. Higher-risk patients may be treated with cytoreductive agents such as hydroxyurea and interferon as first-line therapy.

The Janus kinase inhibitor ruxolitinib (Jakafi) may be used as second-line therapy based on results from the RESPONSE trial (NCT01243944) that showed efficacy in patients who failed to respond to hydroxyurea. The primary end point of hemocrit control at 32 weeks was achieved in 21% of patients receiving ruxolitinib versus only 1% of those receiving standard therapy, as well as greater overall hemocrit control and more patients with spleen reduction.

Even with cytoreductive therapy, high levels of therapeutic phlebotomy may be required, which increases the risk of thrombosis in these patients, Ginzburg says.

 Polycythemia vera is a chronic myeloproliferative disease, one of several. It is associated often, given its chronicity, with a long period of survival, including sometimes up to 20 years post diagnosis. There are groups of patients both better categorized into low risk versus high risk. The low-risk patients are younger and do not have a history of thromboembolic events. The higher-risk population is older and/or has a history of a thromboembolic event.

Patients are often treated with therapeutic phlebotomy, that's the mainstay of treatment, especially in the low-risk population. In the high-risk population, patients are often treated with cytoreductive agents of which hydroxyurea and interferon are both first line and ruxolitinib [Jakafi] is considered second line. So, despite cytoreductive therapy, some patients still require high levels of therapeutic phlebotomy and there is some risk of thrombosis that's higher in patients who require a higher rate of therapeutic phlebotomy.

Yelena Ginzburg, MD, discusses the prognosis and standard-of-care treatment in patients diagnosed with polycythemia vera. 

Yelena Ginzburg, MD | Authors

Articles

Rusfertide May Reduce Need for Therapeutic Phlebotomy in Polycythemia Vera

Risk Assessment and Treatment of Polycythemia Vera