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Polycythemia Vera: Burden of Illness
San Diego—Polycythemia vera (PV) is a bone marrow disorder in which the body produces an excessive amount of red blood cells. It is a chronic, progressive myeloproliferative neoplasm that affects approximately 100,000 people in the United States. It is characterized by clonal expansion of a hematopoietic progenitor, erythrocytosis, often leukocytosis and/or thrombocytosis, and nearly always an activating mutation in Janus kinase (JAK) 2 [Ann Hematol. 2014;93(12):1965-1976.
During a science and innovation theater, Ahmad B. Naim, MD, senior medical director, medical affairs, Incyte Corporation, discussed the signs and symptoms, disease management, and the prognostic risk and clinical considerations for patients with uncontrolled PV. Incyte Corporation sponsored the event.
Among patients treated for PV, a subset of patients has uncontrolled disease. For example, more than 1 in 4 have hematocrit levels ≥45% despite treatment. Resistance to hydroxyurea has emerged as an adverse prognostic factor in PV. Also, some patients may experience increasing signs and symptoms of disease. Risk assessment in PV is based on patient’s age (≥60 years), thrombosis, and traditional cardiovascular risk factors (eg, arterial hypertension, diabetes mellitus, smoking). In addition, patients with PV have an increased risk of mortality compared with the general population. Dr. Naim said that in a population-based study, the life expectancy of patients with PV was reduced by 36% compared with that of the general population. Cardiovascular deaths and malignancies also account for a large proportion of deaths in PV. He cited a study from the International Working Group-Myeloproliferative Neoplasms Research and Treatment [Leukemia. 2013;27(9):1874-1881]. This large, retrospective study was based on the 2008 World Health Organization (WHO) diagnostic criteria for PV. Of the 1545 patients, 347 (23%) had died by the time of analysis, of which 164 had a known cause of death (eg, acute leukemia, second malignancies, thrombotic complications, heart failure).
Polycythemia Vera Presentation
Dr. Naim reviewed the clinical and hematologic features of PV. He said that patients present with 3 main clinical scenarios:
• Diagnosis by chance (eg, asymptomatic)
• More than 30% have thrombosis at initial pre- sentation; thrombotic events may have occurred many years before diagnosis, and may continue to occur for years after diagnosis
• Diagnosis resulting from disease-related symptoms, which may be present in up to 85% of patients
PV is associated with a significant symptom burden. Fatigue is the most common and intense symptom reported by 85% of patients. Some patients (65%) may experience intractable pruritus (ie, itch), which can be debilitating. Splenomegaly (ie, enlargement of the spleen) is observed in 30% to 40% of patients at presentation. “Cytokine elevations are responsible for a lot of the symptoms,” he said.
Clinical presentation that warrants further evaluation for PV includes splenomegaly (with or without thrombocytosis and leukocytosis), thrombotic and hemorrhagic events, and systemic symptoms (eg, fatigue, pruritus, and night sweats). Other criteria for diagnosis of PV include elevated hemoglobin, elevated red cell mass, complete blood count (CBC), and bone marrow biopsy. “CBCs are the most common way to workup the patient,” said Dr. Naim.
Diagnosis and Management of Polycythemia Vera
Dr. Naim reviewed the 2008 WHO diagnostic criteria for PV, which he noted are up for revision. The diagnosis of PV requires meeting either both major criteria and 1 minor criterion or the first major criterion and 2 minor criteria.
The major criteria:
1. Hemoglobin >18.5 g/dL in men and >16.5 g/dL in women
2. Presence of the JAK2V617F
The minor criteria:
1. Bone marrow biopsy showing hypercellularity
2. Serum erythropoietin below the normal range
3. Endogenous erythroid colony formation in vitro
“If criteria are met, PV is likely,” he said. “If criteria are not met, additional workup may be required for confirmation.”
Clinical considerations in managing PT include controlling and maintaining hematocrit levels consistently <45%, treating complications of thrombosis and hemorrhage, reducing thrombotic risk, and managing symptoms.
Dr. Naim noted that at least 25% of PV patients do not achieve target hematocrit level <45%. Furthermore, the ECLAP [European Collaboration on Low-dose Aspirin in Polycythemia Vera] study found that 46% to 49% of patients do not meet the hematocrit goal.
Financial Burden
Healthcare costs and resource use in PV is significant, according to Dr. Naim who discussed a study from a large, retrospective chart review of a US database that included 5752 patients with PV and 5752 matched controls. The researchers found that health- care costs were higher in patients with PV compared with matched controls. PV-related healthcare costs were approximately $7000 more than those of matched controls. PV was associated with significantly elevated costs for all healthcare components that were evaluated, including hospital inpatient, outpatient, emergency room, and pharmacy expenses compared with matched controls. Furthermore, hospital inpatient admissions were significantly longer for patients with PV compared with matched controls (mean, 1.67 days vs 0.76 days, respectively; P<0.0001). A significantly greater proportion of patients with PV versus matched controls visited the emergency room (31% vs 22%, respectively; P<0.0001).—Eileen Koutnik-Fotopoulos
