Symptom burden a key component of disease control assessment in polycythemia vera
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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.
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.”
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.