Polycythemia Vera Management: Addressing the Burden of Symptoms and Phlebotomy Dependence

There is growing recognition of the need to address the persistent decline in quality of life experienced by many patients with polycythemia vera.

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Managing polycythemia vera (PV) is a delicate balance between controlling life-threatening clotting risks and preserving patients’ quality of life.¹ A review published in Clinical Lymphoma, Myeloma & Leukemia highlights that while therapeutic phlebotomy and cytoreductive therapies reduce blood thickness and clotting risks, they often come with significant trade-offs: chronic symptoms, dependence on frequent medical visits, and limited relief from the disease’s inflammatory effects.

PV is a rare type of blood cancer affecting 50 per 100,000 people in the US, most commonly diagnosed in individuals over the age of 60.² It’s characterized by an overproduction of red blood cells, which raises the risk of blood clots and can complicate circulation and oxygen delivery. Despite its life-long nature, PV can often be managed in ways that allow patients to live with near-normal life expectancy.¹

However, persistent challenges impact treatment efficacy and quality of life for those with PV, necessitating continued innovation in treatment approaches. This review examined the primary factors complicating PV management and emphasizes the need for strategies that prioritize symptom relief and enhance patient autonomy.

The Role of JAK/STAT Pathway Activation and Its Impact on Symptoms

The review looked at the constitutive activation of the JAK/STAT pathway, a signaling pathway that regulates cell growth and immune responses. This activation not only drives the disease’s progression but also results in chronic inflammation, which brings a host of symptoms such as fatigue, itching, and night sweats. As a result, patient quality of life often diminishes significantly, and current treatments have shown limited effectiveness in mitigating them, leaving many with persistent, life-impacting discomfort.

Phlebotomy: An Essential Burden of PV Care

To prevent thrombotic events, patients typically undergo therapeutic phlebotomies, a process where blood is drawn to maintain hematocrit levels below 45%. While essential in managing clotting risks, the procedure is not only physically demanding for many patients but can also be difficult to tolerate over time. Additionally, the frequency of these treatments, coupled with the need for regular hematocrit monitoring, creates a dependency on the health care system. This ongoing requirement places constraints on patients’ autonomy and freedom, as they must structure their lives around regular clinic visits and invasive procedures.

“For example, among a cohort of 865 patients in the REVEAL study assessed at baseline, patients reported having an average of 2.5 phlebotomies in the 6 months prior to enrollment, and that mean total treatment time can be up to 4 hours for each phlebotomy procedure, leading to missed work for those who were employed,” the authors stated. “More than half of patients reported experiencing fatigue within 24 hours after a phlebotomy, with bruising, dizziness, and dehydration being additional commonly reported effects.”

Exploring Cytoreductive Therapy to Reduce Phlebotomy Needs

To reduce the need for phlebotomy, the authors explained that many clinicians turn to cytoreductive therapies like hydroxyurea and interferon. While these therapies effectively lower red blood cell counts, they have not consistently been shown to alleviate PV-related symptoms or meaningfully improve quality of life. This leaves patients in a cycle of managing one set of adverse effects and symptoms only to encounter others, with no definitive relief from the burden of either phlebotomy or the disease’s inflammatory symptoms.

“Although guideline-based therapy can help to effectively manage hematocrit levels for many patients, treatment discontinuation remains a major challenge,” the research stated. “Rates of permanent discontinuation for hydroxyurea in studies with multi-year follow-up periods range from 17.5% to 20%, and many patients with PV interrupt and restart hydroxyurea treatment throughout the course of their disease.”

Shifting the Treatment Paradigm to Improve Quality of Life

While PV management remains focused on reducing the risk of thrombotic events, there is growing recognition of the need to address the persistent decline in quality of life experienced by many patients. Researchers are actively pursuing disease-modifying therapies that could potentially alter the disease course. However, nearer-term solutions are also critical. Emphasis on strategies that minimize or eliminate the need for frequent phlebotomy—while avoiding additional adverse effects—could represent a meaningful step forward in enhancing patient autonomy and well-being.

“Currently, there are no disease-modifying treatment options (i.e., a treatment that corrects the JAK2 V617F driver mutation in affected cells) for patients with PV,” the authors concluded. “However, emerging treatments that aim to reduce or eliminate the need for frequent phlebotomy and improve disease-related symptoms may become a critical component in the current standard of care for PV.”

References

1. Kuykendall AT, Fine JT, Kremyanskaya M. Contemporary challenges in polycythemia vera management from the perspective of patients and physicians. Clin Lymphoma Myeloma Leuk. 2024;24(8):512-522. doi:10.1016/j.clml.2024.04.003

2. Polycythemia vera. Cleveland Clinic. Updated April 25, 2022. Accessed November 5, 2024. https://my.clevelandclinic.org/health/diseases/17742-polycythemia-vera