Category Archives: Polycythemia Vera

4 Ways Polycythemia Vera Can Affect Your Quality of Life — and What You Can Do About It

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By Jessica Migala
Published on February 14, 2025
by Walter Tsang, MD
Just like any chronic health condition, polycythemia vera (PV) can have a negative impact on your everyday life. Research has shown that PV is associated with a lower quality of life in measures, including health, cognitive, emotional, and physical functioning.

Symptoms such as fatigue, itchy skin, and mental health issues can make it difficult to function, but they can be managed. “This is a chronic condition that people can live with,” says Jacqueline S. Garcia, MD, a medical oncologist at Dana-Farber Cancer Institute in Boston.

Here are some common challenges of living with PV and ways to cope, so you can stay healthy and live well as you manage this condition.

1. Fatigue Can Interfere With Daily Activities

Fatigue is one of the most common symptoms of PV. “Polycythemia vera is a blood disorder that stems from an error in the bone marrow,” says Dr. Garcia. As a result, bone marrow overproduces red blood cells, causing the body to use up your iron supply. This results in iron deficiency, which leads to fatigue, she explains.
Another factor that can contribute to fatigue is phlebotomy treatment, which is a procedure that involves drawing blood to reduce blood cells and blood volume. A common side effect of this treatment is increased fatigue and iron deficiency, according to Garcia.

The degree of fatigue can vary from one person to another and depend on age, menopausal status, other health conditions — such as cardiovascular disease or diabetes — and more factors, says Garcia.

What to do about it: When it comes to polycythemia vera fatigue, research found that fatigue was a bigger problem for people who had a higher BMI, continued to drink alcohol or use tobacco, and didn’t exercise.

Maintaining healthy lifestyle habits may help you feel more energized every day. For instance, Garcia recommends exercising in moderation, as long as you have your doctor’s okay and don’t push yourself if you feel faint.

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Getting Closer to Disease Modification in Polycythemia Vera

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February 2025 Vol 11 No 1

Dr. Lucia Masarova

Polycythemia vera was first recognized by French physician Louis H. Vaquez in 1892 and was known then as maladie de Vaquez.1 The name poly-cyt-[h]emia originates from the Greek and Latin, and literally means many-cells-in the blood. In 1951, Dr. William Dameshek included polycythemia vera in the category of classic Philadelphia chromosome–negative myeloproliferative disorders (now classified as myeloproliferative neoplasms, MPNs; myelo refers to the bone marrow, proliferative refers to rapid growth of blood cells, and neoplasm describes abnormal and excessive growth). It is the only one among the 3 classic MPNs that exhibits erythrocytosis, the increased production of red blood cells. Polycythemia vera is a condition associated with overproduction of all blood cells, including white cells and platelets.

Polycythemia vera is a chronic, incurable disease of the hematopoietic stem cells, the primary cells that can develop into different types of blood cells and are responsible for the production of blood cells during a human’s entire life. It is a clonal disease, meaning it occurs when a mutated hematopoietic stem cell starts making clones—cells with the same genetic mutation. Most affected patients can live a relatively normal and long life.

A breakthrough discovery of a genetic “driver” of polycythemia vera was made in 2005—a mutation in the JAK2 gene was found in 95% of cases, typically JAK2V617F, a mutation that leads to the constitutive activation of the JAK-STAT protein pathway causing unregulated overproduction of hematopoietic cells. This discovery led to improved understanding of the biology, pathogenesis, and long-term behavior of the disease and initiated numerous efforts to develop novel therapies focused on the inhibition of the JAK-STAT pathway.

The abnormal function of the immune system and the subsequent increased inflammation, powerfully driven by the JAK-STAT pathway as the major regulator of inflammatory signaling, contribute to disease progression and an impaired quality of life. Despite the relatively slow progression of the disease course in most patients, the disease possesses its challenges and risks, including a lifetime risk of developing thrombosis (blood clots); the evolution into myelofibrosis, a chronic type of leukemia; or development into acute leukemia. Both blood clots and leukemia are consequences that can shorten life expectancy significantly.

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Genetic Links to High Altitude Found to Reduce Inflammation, Speed Response to PV Therapy

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December 10, 2024

Author(s): Mary Caffrey

Questions about why an indigenous population living the Andes Mountains of South American had elevated hemoglobin led to the discovery that a variant linked to living at high altitude is also tied to reduced inflammation, as well as improved response to a therapy used to treat myeloproliferative neoplasms (MPNs).1

Jihyun Song, PhD | Image credit: University of Utah

The research to be presented today at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California, could lead to more precise treatments for polycythemia Vera (PV) and essential thrombocythemia (ET). Today, these 2 are treated with ropeginterferon-α (Besremi), and the work led by Jihyun Song, PhD, of Huntsman Cancer Institute at the University of Utah, now shows that populations with Andean enriched NFKB1 haplotype respond better to ropeginterferon-α.

The study has been accepted for publication in Nature Communications.

PV and ET are both associated with overproduction of blood cells; PV causes the bone marrow to produce too many red blood cells, while ET produces too many platelets. Both PV and ET can lead to chronic inflammation, increase the risk of blood clots, and progress to leukemia. These conditions also increase hypoxia-inducible factors (HIFs), which can impact the survival of cancer cells in low-oxygen environments.

At a press briefing prior to Song’s presentation today, senior author Josef T. Prchal, MD, a physician scientist who holds the Charles A. Nugent, MD, and Margaret Nugent Endowed Professorship in Medicine/Hematology at the University of Utah, explained that the genetic variants that developed over time to allow the Aymara people survive in the Andes can be seen in some other populations—and they correlate with some differences in MPN phenotypes.

Josef Prchal, MD | Image credit: Photo supplied by ASH

“Our study suggests that with genotyping, the NFKB1 variant can be used as a biomarker for determining which patients may be more or less responsive to ropeginterferon-α treatment,” Prchal said.

He opened his remarks with an overview of how populations evolve with their environments; not only the Aymara but also Tibetans and Ethiopians have adapted to altitude in different ways, which he explored in earlier papers in Science2 and Nature Genetics,3 among others.

It is known that when humans spend time high altitude, their bodies adapt to reduced oxygen levels by increasing hemoglobin concentrations in the blood. This allows the body to carry more oxygen. Prchal explained how Song took this knowledge further. “We set up to try to find the gene which explains the hemoglobin,” he said.

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Ten years of experience with ruxolitinib since approval for polycythemia vera: A review of clinical efficacy and safety

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Lucia Masarova MD1 | John Mascarenhas MD, MS2 | Raajit Rampal MD, PhD3 | Wilson Hu MD4 | Robert A. Livingston MD, MPH4 | Naveen Pemmaraju MD1

Abstract
The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2014 for the treatment of patients with polycythemia vera (PV) who have an inadequate response to or intolerance of hydroxyurea (HU). PV is a chronic myeloproliferative neoplasm defined by primary absolute erythrocytosis, bone marrow hypercellularity, and JAK mutations such as JAK2V617F. Patients with PV experience burdensome symptoms and are at risk of thromboembolic events, in particular those with resistance to or intolerance of initial treatments such as HU. Other risks for patients with PV include progression of disease to more aggressive forms with worse prognoses, such as myelofibrosis or blast‐phase myeloproliferative neoplasms. This review summarizes the efficacy and safety of ruxolitinib from key phase 2 and 3 trials (MAJIC‐PV, RESPONSE, RESPONSE‐2, RELIEF, and Ruxo‐BEAT), large real‐world studies, and a decade of postmarketing surveillance safety data. The authors focus on improved blood count control, rates of thromboembolic events, symptom improvement, and markers of disease modification such as reduction of JAK2V617F allele burden in patients treated with ruxolitinib. They also discuss the well‐characterized safety profile of ruxolitinib regarding hematologic and other adverse events of interest. In the 10 years since its approval, ruxolitinib remains a safe and effective standard‐of‐care treatment for PV. As the treatment landscape for PV continues to evolve in the coming years, the efficacy and safety profiles of ruxolitinib suggest it will remain a
preferred treatment as monotherapy and as a potential backbone of future combination regimens.

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Rusfertide Reduces Phlebotomy Need, Improves Symptom Control in Polycythemia Vera

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November 21, 2024

Author(s): Alexandra Gerlach, Associate Editor

Rusfertide (Takeda; Protagonist Therapeutics Inc) controlled erythrocytosis, maintained a hematocrit of less than 45% and reduced or eliminated the use of phlebotomy in patients with polycythemia vera (PV), according to data from the REVIVE trial (NCT04057040). Published in The New England Journal of Medicine, the results suggest the agent could become an additional therapeutic tool to reduce disease-related symptoms and the need for phlebotomy.1,2

Blood cells | Image Credit: © Ifti Digital – stock.adobe.com

PV is a rare type of blood cancer characterized by the overproduction of red blood cells in the bone marrow, contributing to blood clots, as well as the development of other blood disorders, such as myelofibrosis (MF). Both PV and MF are types of BCR‐ABL1‐negative myeloproliferative neoplasms with shared mutations and are associated with risk of thrombosis, hemorrhagic complications, and progression to acute myeloid leukemia. Approximately 1 in 4 patients with PV will develop MF, which is referred to as post–polycythemia vera myelofibrosis.3-5

Standard-of-care treatment for PV focuses on symptom reduction including treatments for to reduce itching or control blood cell counts, using agents such as hydroxyurea (Droxia; Bristol Myers Squibb) or ruxolitinib (Jakafi; Incyte Corp). The most common treatment for PV is frequent blood withdrawals to decrease blood volume, which is done via phlebotomy.5

Rusfertideis is an injectable, peptide mimetic of hepcidin. Hepcidin, produced in the liver, is a master regulator of iron trafficking. Some preclinical models suggest that increasing hepcidin could help control red blood cell production in patients with PV. In the phase 2 REVIVE trial, rusfertide demonstrated favorable safety and efficacy, with the potential to greatly decrease or eliminate the need for phlebotomy.2

The international, phase 2 REVIVE trial is divided into 2 parts. In part 1, patients were enrolled in a 28-week dose-finding assessment of rusfertide. In part 2, a double-blind, randomized withdrawal period, patients were assigned 1:1 ratio to receive either rusfertide (n = 30) or placebo (n = 29) for 12 weeks. The primary end point was response, which was defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Outcomes were reported by patients and were assessed using the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).2

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Ropeginterferon Alfa-2b Demonstrates Similar Pharmacokinetics Across Ethnic Groups With PV

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Andrea S. Blevins Primeau, PhD, MBA

The pharmacokinetic (PK) profile of ropeginterferon alfa-2b (Ropeg) was consistent between Chinese and Caucasian populations with polycythemia vera (PV), according to a modeling study published in Frontiers in Pharmacology.

These results confirm “its efficacy and safety in the global treatment of PV” and “support the broader application of Ropeg in diverse patient populations,” the researchers wrote in their report.

The researchers used data from studies of Ropeg in subjects without myeloproliferative neoplasms (MPN) and among patients with PV to perform modeling analyses for PK parameters, efficacy, and safety in Chinese and Caucasian populations.

PK was assessed using a population PK model using data from phase 1 studies of Chinese and Caucasian volunteers without MPN. There was no significant difference in Ropeg clearance, volume of distribution, or absorption rate between the groups.

In an exposure-response analysis, data from phase 2 clinical trials were used to inform the model. A higher complete hematologic response (CHR) rate was observed in the study of Chinese patients due to a higher starting dose. The CHR was 63% among Chinse patients and 35% among Caucasian patients at 24 weeks. The CHR rates reported from the trials were similar at 61.2% and 27%, respectively.

Our results support the use of Ropeg as an effective and tolerable first-line treatment for PV regardless of ethnic variations.

This “indicates that there is a similar exposure-response relationship between Chinese and Caucasian populations,” the researchers explained.

Phase 2 data were also used to inform the exposure-safety analysis. In the Chinese group, the high dose level of Ropeg was associated with asymptomatic higher liver transaminase levels. There was no association between exposure and gamma-glutamyl transferase, white blood cell count, or neutrophil count.

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Ruxolitinib Provides Better Efficacy Than Best Available Therapy in Polycythemia Vera

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Andrea S. Blevins Primeau, PhD, MBA
According to the results of a systematic review and meta-analysis published in the journal APMIS, patients with polycythemia vera (PV) achieved greater hematocrit control and improved symptoms with ruxolitinib compared with best available therapy (BAT). Ruxolitinib was also associated with higher rates of nonmelanoma skin cancer, anemia, and certain infections.

Researchers identified 6 studies, including 4 randomized controlled trials and 2 observational studies, comprising 1061 patients with PV during the systematic review of reports published through 2023. The meta-analyses used a risk ratio (RR) to estimate effect size.

All patients received treatment with ruxolitinib or BAT, which included hydroxyurea, interferon, pegylated interferon, pipobroman, or anagrelide. The primary outcomes were hematocrit control and complete hematologic response (CHR).

In the cohort, the median age was 66.4 years and 72.8% of patients were male. There were 41.6% of patients were treated with ruxolitinib, 34% were hydroxyurea resistant, and 60% were hydroxyurea intolerant.

Higher rates of hematocrit control were observed in the ruxolitinib group compared with the BAT group (RR, 1.907; 95% CI, 1.135-3.205; P =.015). Ruxolitinib was also associated CHR compared with BAT (RR, 1.965; 95% CI, 1.025-3.768; P =.042).

Among patients with hydroxyurea-resistant or intolerant PV, higher rates of CHR (RR, 2.28; 95% CI, 1.36-3.84; P <.01), at least a 50% reduction in the MPN-SAF score (RR, 3.19; 95% CI, 1.21-8.46; P =.02), and PGIC score (RR, 6.86; 95% CI, 3.45-13.63; P <.01).

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Neutrophil-to-lymphocyte ratio as a prognostic indicator of mortality in Polycythemia Vera: insights from a prospective cohort analysis

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Tiziano Barbui, Alessandra Carobbio, Arianna Ghirardi, Francesca Fenili, Maria Chiara Finazzi, Marta Castelli, Alessandro M. Vannucchi, Paola Guglielmelli, Alessandro Rambaldi, Naseema Gangat & Ayalew Tefferi

Abstract

We analyzed the neutrophil-to-lymphocyte ratio (NLR) in 1508 patients with PV and found that those with an NLR ≥ 5 were generally older, had a longer disease history, and had higher cardiovascular risk factors, more arterial thrombosis, and more aggressive blood counts, indicating a more proliferative disease. NLR was an accurate predictor of mortality, with patients with NLR ≥ 5 having significantly worse overall survival and more than twice the mortality rate compared to those with NLR < 5. Multivariable models confirmed that increasing age, previous venous thrombosis and NLR ≥ 5 were strong predictors of death, further influenced by cardiovascular risk factors. We examined the interaction between NLR and the number of cardiovascular risk factors and found a progressive trend of increased mortality risk for NLR values ≥ 5 in addition to the presence of more than one risk factor. In conclusion, patients with NLR ≥ 5 require careful monitoring and management of cardiovascular risk factors because they increase mortality when associated with progressive levels of NLR.

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Jakafi, Pegasys Combination Beneficial in Newly Diagnosed Polycythemia Vera

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November 4, 2024

Author(s): Alex Biese

Fact checked by: Spencer Feldman

Among patients with who were newly diagnosed polycythemia vera (PV), treatment with Jakafi (ruxolitinib) and low-dose Pegasys (pegylated interferon alfa-2a) was found to be beneficial, resulting in high rates of hematologic and molecular response, research has shown.

Findings from the two-year end-of-study results of the phase 2 COMBI II clinical trial, published in Blood Advances, showed that the combination treatment was associated with improvements to patients’ cell counts with what researchers described as acceptable toxicity.

Researchers utilized the participation of 25 patients with PV, with a median age of 70 years. According to the study, 14 patients (56% of participants) achieved remission at 24 months, with three (12%) attaining complete remission and 11 (44%) reaching partial remission. Researchers reported what they observed as significant reductions to abdominal discomfort, night sweats, itching and bone pain, while the median JAK2V617F VAF was decreased from 47% to 7% and 60% of patients achieved molecular remission.

One of the 25 patients dropped out of the study within two years, while one patient discontinued both drugs while two patients each discontinued Jakafi and Pegasys and continued stand-alone therapy with the other drug.

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Ruxolitinib Plus Pegylated Interferon Alfa-2a Show Promise in Newly Diagnosed Polycythemia Vera

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November 1, 2024

Author(s): Alexandra Gerlach, Associate Editor

Ruxolitinib (Jakafi; Incyte Corp) in combination with pegylated interferon alfa-2a demonstrated efficacy and tolerability in patients with newly diagnosed polycythemia vera (PV). According to the 2-year end-of-study results from the phase 2 COMBI 2 clinical trial (EudraCT2018-004150-13), the treatment improved cell counts, bone marrow cellularity, and fibrosis in patients with PV.1

In the phase 2 COMBI 2 trial, researchers evaluated the safety and efficacy of ruxolitinib and low-dose peg-IFN-α2a in patients with newly diagnosed PV.

Image Credit: © MdBabul – stock.adobe.com

PV is a chronic, progressive myeloproliferative neoplasm characterized by the overproduction of red blood cells. The excess cells thicken the blood, slowing its flow and contributing to serious complications, such as blood clots. Almost all patients with PV have the JAK2V617F mutations, and the JAK2V617F variant allele frequency (VAF) is key for determining outcomes, including thrombosis and progression to myelofibrosis.2-4

Ruxolitinib is a Janus kinase inhibitor approved by the FDA in 2011 and is indicated for the treatment of patients with high-risk MF with reduced abnormal expression of PF4, which can lead to decreased fibrosis. It is additionally indicated as a second-line treatment of PV for patients who have an inadequate response to or cannot tolerate hydroxyurea. In the COMBI 2 trial, researchers assessed the efficacy of ruxolitinib in combination with pegylated interferon alfa-2a (peg-IFN-α2a) (Pegasys ProClick; Genentech), an injection commonly used to treat hepatitis B and C infections. According to data from prior studies, peg-IFN-α2a has been shown to induce durable hematologic and molecular remissions in patients with PV. However, approximately 20% to 40% of patients are intolerant or show limited response to peg-IFN-α2a.5-8

In the phase 2 COMBI 2 trial, researchers evaluated the safety and efficacy of ruxolitinib and low-dose peg-IFN-α2a in patients with newly diagnosed PV in an effort to counterbalance intolerance to peg-IFN-α2a. The primary end point was safety, with secondary end points including efficacy, based on hematologic parameters, quality-of-life measurements, and JAK2V617F variant allele frequency (VAF).8

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