Investigating Mortality and Causes of Death of Patients With Polycythemia Vera

Polycythemia vera (PV) is a chronic form of blood cancer that is relatively rare in the United States, with about 150,000 individuals living with the disease. Research over the past decade has shown that PV can be associated with a reduction in survival compared with age- and gender-matched population controls, demonstrating the importance of understanding mortality and causes of death among patients with PV.

For this reason, a multicenter, noninterventional, prospective observational study of patients with PV in US-based clinical practices was conducted and presented at the 62nd American Society of Hematology Annual Meeting & Exposition. The research analyzed the final data from the REVEAL study (NCT01252953) in order to characterize the deceased patients, survival by risk, and causes of death during the study.

PV is characterized by the mutation of the JAK2 gene, causing an overproduction of red blood cells, an increase in blood clotting risk, and later risks of disease transformation, in about 99% of these patients. In prior studies, survival estimates of patients with PV have approached or exceeded 20 years from diagnoses. However, survival in patients with PV has generally been evaluated retrospectively, making specificity around cause of death more difficult to determine.

“Over the last 25 years, there’s been a number of large cohort studies. The study design and the patient population differ, but there are a few consistencies,” said Brady Stein, MD, MHSc, an associate professor of medicine in hematology and oncology at Feinberg School of Medicine at Northwestern University. “In general, what we’re seeing is that the typical survival for patients with PV is, depending on these studies, between 15 and 20 years.”

Stein explained that in these studies, some patients were older at their diagnoses with higher risk features that meant they had a survival of 10 years, whereas other younger patients may have had a survival of 30 years. However, these studies suggested that there’s a survival of approximately 15 to 20 years for patients with PV in general.

Specifically, Stein noted that the REVEAL study is unique among this body of research because it is a large prospective study with over 2500 patients. The study is also potentially more representative of clinical practice patterns in the United States because most patients were followed in community hematology and oncology practices from more than 220 sites.

“The overwhelming majority of patients were cared for in community practices, so this is kind of a real-world cohort, and I think the study design is also relatively unique in that it’s prospective,” Stein said. “A lot of the studies before had been retrospective lookbacks. So, it’s not that causes of death haven’t been reported, but the [REVEAL] study design and patient cohort are unique.”

In current practice, the common treatment for PV is phlebotomy and aspirin. Additionally, patients may also be placed on cytoreductive therapies to lower blood count, with hydroxyurea being the most common medication used in the United States.

The REVEAL study results showed that the estimated 4-year mortality for patients with PV was approximately 10%, which was notable considering the mean age at enrollment was approximately 66 years.

“The patients who died were older at diagnosis, which is not necessarily surprising since they fell into a higher risk category because of their age or, to a lesser extent, because of their clotting history,” said Stein. “They had a more complicated set of comorbid illnesses, so not just polycythemia vera, but other issues like cardiovascular disease, respiratory diseases, or other malignancies. So, the finding of note was confirming what many studies have shown— that age and blood clotting history are important.”

Stein explained that consistency with prior studies was interesting, considering the unique nature of the REVEAL study.

“Despite having a different study design and a pretty unique cohort, when looking back at a number of the largest studies that look at survival and causes of death, we saw some of the same things,” she said.

In the REVEAL study, the investigators found that approximately one-third of the deaths were due to thrombotic complications, whereas 6 months prior to death, more than a quarter of patients had elevated hematocrit levels or uncontrolled myeloproliferative disorders. Additionally, compared with patients who were alive at the time of the study completion, patients who had died had higher-risk disease with higher rates of comorbid conditions.

“In our study, the most common causes of death were due to vascular complications; just behind in terms of other causes were transformations to leukemia or other solid tumors. Again, when you look at a lot of the prior studies, these are the 3 common things that can happen to patients like ours with PV,” Stein said.

Additionally, the investigators observed a high rate of respiratory disorders among the deceased population, both as comorbidities and causes of death. They noted that such a high rate had not been well characterized in previous PV mortality studies, demonstrating the need for further investigation.

REFERENCE
Stein BL, Patel K, Scherber RM, Yu J, Paranagama D, Miller CB. Mortality and causes of death of patients with polycythemia vera: analysis of the Reveal prospective, observational study. Paper presented at: 62nd American Society of Hematology Annual Meeting & Exposition; December 5-8, 2020; virtual. Accessed January 12, 2021. http://ash.confex.com/ash/2020/ webprogram/Paper137144.html