Anemia in the pediatric patient
Rusfertide Receives Breakthrough Therapy Designation For Treatment Of Erythrocytosis In Patients With Polycythemia Vera
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Symptom Burden A Key Component Of Disease Control Assessment In ...
November 08, 2019
5 min read
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Michael R. Grunwald
Patients with polycythemia vera can experience high symptom burden even if their blood counts are controlled, according to an analysis from the prospective, observational REVEAL study.
Consequently, clinicians should regularly monitor symptom burden rather than solely relying on blood counts to assess disease control, researchers concluded.
"Historically, much of the focus on treating patients with polycythemia vera has been upon controlling the hematocrit, as well as the other blood counts," researcher Michael R. Grunwald, MD, chief of the leukemia division in the department of hematologic oncology and blood disorders at Levine Cancer Institute at Atrium Health, as well as a HemOnc Today Next Gen Innovator, told HemOnc Today. "Control over blood counts, of course, remains a very important goal. We know that, in particular, controlling the hematocrit leads to lower rates of thrombosis in polycythemia vera.
"However, with increased knowledge about the frequency and severity of polycythemia vera-related symptoms, it has also become important to understand whether achieving the target range for patients' blood counts will also help control their symptoms," Grunwald added. " It turns out that this is not always the case."
Polycythemia vera is a rare, slow-growing myeloproliferative neoplasm in which the bone marrow makes too many red blood cells. The additional cells thicken the blood, increasing the risk for blood clots.
Symptoms can include fatigue, abdominal discomfort, early satiety, itching, night sweats, fever, bone pain, unintentional weight loss, inactivity and problems with concentration.
Approximately half of patients have disease-related symptoms at diagnosis, and others may develop symptoms later in the disease course, Grunwald said.
Prior research established that myeloproliferative neoplasm-related symptoms can affect productivity.
"It is likely that polycythemia vera-related symptoms have an adverse impact upon health-related quality of life for many patients," Grunwald said.
National Comprehensive Cancer Network guidelines recommend the Myeloproliferative Neoplasm Self-Assessment Form (MPN-SAF) total symptom score — derived from a 10-item symptom burden assessment— be used for symptom monitoring during treatment. However, no prior study had evaluated whether blood count control translated to symptom control.
Grunwald and colleagues assessed the effect of blood count control on symptom burden as measured by MPN-SAF total symptom score for patients enrolled in REVEAL, an ongoing multicenter, noninterventional, nonrandomized study that enrolled 2,510 adults in the United States with polycythemia vera.
The analysis included 1,813 patients (median age, 67 years; range, 22-95; 54.3% men; 90.6% white) who had a complete blood count checked within 30 days prior to at-enrollment completion of the MPN-SAF.
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Median age at diagnosis was 61 years, and median time from diagnosis to study enrollment was 4.1 years (range, 0-39.2). More than half of evaluable patients (57%) had been diagnosed less than 5 years earlier, whereas 18.8% had been diagnosed more than 10 years prior.
The majority of patients were undergoing cytoreductive therapy (94.5%) and were managed with hydroxyurea, phlebotomy or both (87.2%).
One-quarter of evaluable patients (25.8%) had complete hematologic remission upon enrollment, with 89% having at least one controlled blood count and 61.9% having two or more controlled blood counts.
Researchers observed no statistically significant differences in mean MPN-SAF total symptom scores between patients in different blood count control groups (20.2 for those with uncontrolled counts, 18.7 for those with at least one controlled count, 18.7 for those with at least two controlled counts and 19.1 for those with complete hematologic remission).
A sensitivity analysis performed among patients with zero, one, two or three controlled blood counts showed no significant association between total symptom scores and the number of controlled counts.
"While this is new information, the results presented in [this] manuscript are not terribly surprising," Grunwald told HemOnc Today. "It makes sense that controlling the counts does not necessarily lead to symptom control. Cytoreductive techniques may not change the abnormal cytokine balance that can exist in polycythemia vera, and cytokines may be responsible for many [disease]-related symptoms."
Investigators reported similar mean total symptom scores regardless of which specific blood counts were controlled, with the exception of white blood cell count.
Mean white blood cell counts were 6.83 x 109/L in the controlled group and 16.33 x 109/L in the uncontrolled group. Mean total symptom scores were 18 for patients with controlled counts vs. 20.2 for those without (P = .0036). Grunwald said that this difference in symptoms between patients with controlled and uncontrolled white blood cell counts might benefit from further investigation.
Women reported higher mean total symptom scores than men (21.5 vs. 16.6); however, results showed no significant differences in mean scores by sex between the controlled and uncontrolled blood count groups.
Severity of individual symptoms — with the exception of night sweats and pruritus — did not vary by complete hematologic remission status or the number of controlled blood counts.
"Emerging data demonstrate clear relationships between specific myeloproliferative neoplasm symptoms and specific cytokines," Grunwald and colleagues wrote. "Additional research might well be warranted to determine whether severe night sweats or pruritus, in the context of uncontrolled blood counts, have unique cytokine signatures."
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Researchers acknowledged study limitations, including the fact the analysis was designed to assess the relationship between symptom control and blood count control at a single time point. Also, most patients had total symptom scores of 18 to 20 — characterized as an intermediate symptom burden — and the correlation between blood count control and mean total symptom scores may have been affected by patients who had overlapping symptoms from comorbidities.
Investigators will continue to analyze data collected from the REVEAL study, which Grunwald said is providing new insights into the course of polycythemia vera and care patterns for patients with the disease.
"The results of this study have the potential to bring more attention to the array of symptoms experienced by patients with polycythemia vera," Grunwald told HemOnc Today. "When patients are experiencing significant symptoms, providers should address these when possible. There are circumstances in which medications and/or other interventions can help control polycythemia vera symptoms." – by Mark Leiser
Reference:
Grunwald MR, et al. Clin Lymphoma Myeloma Leuk. 2019;doi:10.1016/j.Clml.2019.06.001.
For more information:
Michael R. Grunwald, MD, can be reached at Leukemia Section, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, 1025 Morehead Medical Drive, Suite 200, Charlotte, NC 28204; email: michael.Grunwald@atriumhealth.Org.
Disclosure: Grunwald reports research funding from Forma Therapeutics, Genentech/Roche, Incyte and Janssen, as well as consultant roles with AbbVie, Agios, Amgen, Cardinal Health, Celgene, Daiichi Sankyo, Incyte, Merck and Pfizer. Please see the study for all other authors' relevant financial disclosures.
Back to Top Srdan Verstovsek, MD, PhD The traditional goal of therapy for polycythemia vera is to decrease the risk for thrombosis, given this is a leading cause of death in this patient population. This is primarily achieved with the use of phlebotomy and/or cytoreductive therapy, which reduces the red blood cell count in blood and, thus, reduces thrombosis risk. Patients also are prescribed low-dose aspirin. Once cytoreductive therapy is prescribed, the goals of therapy also include control of possibly elevated white blood cell count and platelets, or enlarged spleen. Control of quality of life is important in any of these situations and is a key issue to consider during our assessment of patients. Unfortunately, until recently, no specific tool — such as a questionnaire — existed to objectivize quality of life specifically among patients with polycythemia vera. With the advent of such a questionnaire, now we can optimize our assessment and therapy. Grunwald and colleagues did report one perhaps unexpected finding related to application of this questionnaire: poor correlation of quality of life and blood cell count among patients with polycythemia vera. Physicians often assume that control of blood cell count equals control of disease-related symptoms, but apparently this is not so. These provocative results call for all of us involved in the care of patients with polycythemia vera to focus our attention more toward their quality of life rather than focusing solely on blood count control. This is why recently published NCCN guidelines for management of patients with polycythemia vera emphasize regular use of a questionnaire — MPN10 in this case — for monitoring quality of life. Srdan Verstovsek, MD, PhD HemOnc Today Editorial Board Member The University of Texas MD Anderson Cancer CenterDisclosures: Verstovsek reports no relevant financial disclosures.
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GLP-1 Therapy Linked To Improved Outcomes In Polycythemia Vera
GLP-1a treatment in patients with polycythemia vera was linked to significant reductions in mortality, disease progression, and serious complications.
GLP-1a treatment in patients with polycythemia vera was linked to significant reductions in mortality, disease progression, and serious complications.
Treatment with glucagon-like peptide-1 receptor agonists (GLP-1a) was associated with statistically significant reductions in all-cause mortality, progression to myelofibrosis, and venous thromboembolism, as well as lower rates of hospitalization, intensive care unit (ICU) admission and acute kidney injury among patients with polycythemia vera, a type of blood cancer. It was also associated with reduced rates of ischemic stroke or transient ischemic attack, according to findings from a large-scale analysis presented at the 2025 SOHO Annual Meeting.
"Every parameter, both for primary and secondary outcomes, was statistically significantly decreased in patients who were taking a GLP-1a versus those who were not," presenting author Dr. Asfand Yar Cheema, stated in the presentation.
GlossaryGlossary
Myelofibrosis: A disorder where scar tissue builds up in the bone marrow, impairing blood cell production.
Venous thromboembolism (VTE): Blood clots that form in veins, which can travel to the lungs or other organs.
Leukemic transformation: When a blood cancer changes into leukemia, a more aggressive blood cancer.
Glucagon-like peptide-1 receptor agonists (GLP-1a): Drugs used to treat type 2 diabetes and help with weight management that may also affect blood cancer risk.
Acute kidney injury (AKI): Sudden loss of kidney function, often reversible with treatment.
Transient ischemic attack (TIA): A brief episode of stroke-like symptoms caused by temporary disruption of blood flow to the brain.
Randomized controlled trial: A study where patients are randomly assigned to receive a treatment or not to test its safety and effectiveness.
He is a hematology/oncology resident physician at the Cleveland Clinic in Columbus, Ohio.
Among patients with polycythemia vera, those receiving GLP-1a experienced lower rates of several side effects compared with non-users. Acute kidney injury occurred in 11.72% of GLP-1a users versus 16.37% of non-users. Progression to myelofibrosis was 1.70% in users, compared with 3.06% in non-users.
Venous thromboembolism affected 8.33% of patients versus 11.41% in non-users and ICU admissions occurred in 7.45% of users versus 13.35% of non-users; all-cause hospitalizations were 44.82% versus 54.14%, respectively. Mortality was 4.47% among users compared with 8.72% in non-users. Rates of ischemic stroke or transient ischemic attack were 7.45% for patients versus 8.84% for non-users.
Polycythemia Vera Overview and Emerging Role of GLP-1aPolycythemia vera is a chronic myeloproliferative neoplasm, with approximately 95% of patients harboring the JAK2 V617F mutation. Key complications include venous thromboembolism, which occurs in approximately 34% to 41% of patients, progression to myelofibrosis in 10% to 15% and leukemic transformation in 3% to 4%.
GLP-1a, primarily used for glycemic control and weight management, have emerging evidence suggesting they may reduce the risk of myelodysplastic syndromes and myeloproliferative neoplasms in patients with type 2 diabetes mellitus or autoimmune disorders. Preclinical studies indicate these therapies possess antineoplastic and anti-inflammatory activity, producing cytostatic effects and modulation of the JAK/STAT pathway.
Building on the preclinical rationale, investigators aimed to evaluate the association between GLP-1a therapy and key clinical outcomes in patients with polycythemia vera using a large global database. The analysis focused on primary outcomes of all-cause mortality, progression to myelofibrosis and venous thromboembolism. Secondary outcomes included all-cause hospitalizations, intensive care unit admissions, acute kidney injury and transient ischemic attack.
The study was conducted using data from the TriNetX Analytics Network during 2010 to 2022, encompassing 147 healthcare organizations. The population included 5,291 patients with polycythemia vera receiving GLP-1a and 79,027 patients who were not using these therapies.
Patients were followed for three years from the index event, defined as the time of polycythemia vera diagnosis while receiving GLP-1a therapy. The mean duration of therapy among patients was approximately 298 days, with a standard deviation of approximately 162 days.
Study Limitations and Future Research DirectionsOverall, researchers emphasized that the use of GLP-1a led to a therapeutic benefit among patients. Additionally, therapy was linked to reduced healthcare utilization, including fewer hospitalizations and intensive care unit admissions, as well as lower rates of acute kidney injury and transient ischemic attack.
"Even when we looked specifically at patients with type 2 diabetes, GLP-1a showed very beneficial results," Cheema highlighted.
However, the study authors highlight important limitations. Its observational, retrospective design precludes conclusions about causality, and the TriNetX database offers limited clinical granularity. Outcomes may be under-ascertained when patients receive care outside participating institutions, and there is the potential for misclassification or miscoding of diagnoses.
Despite these limitations, the findings suggest a potential therapeutic benefit of GLP-1a in high-risk polycythemia vera patients. Randomized controlled trials are warranted to confirm both the safety and efficacy of therapy in this population.
"Our study suggests a therapeutic benefit of GLP-1a in patients with polycythemia vera… although randomized controlled trials are needed to confirm safety and efficacy in this high-risk population," he concludes.
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