Quality Initiatives for Polycythemia Vera (PV)
Patients with PV may benefit from a Quality Initiative
HU=hydroxyurea; QoL=quality of life.
The Multifaceted Impact of Thrombotic Events in PV
The consequences of TEs are far-reaching
IMPACT ON PATIENTS
HIGHER RISK OF TEs IN PV9
In a population-based study* of 9429 patients with MPNs, including 3001 with PV
at 3 months post-diagnosis
in patients with PV vs matched controls HR, 4.2; CI, 3.5–5.09
*Population-based study based on Swedish Cancer Registry data for 1987-2009 in 9429 patients with MPNs. 9429 MPN patients (PV=3001, ET=3462, PMF=1488, and MPN-U=1478) and 35,820 matched controls were identified and included in the study. Hazard ratio for thrombosis at 3 months post-diagnosis was 4.2 for PV (95% CI, 3.5–5.0) vs 4.0 for all MPNs (95% CI, 3.6–4.4).9
CI=confidence interval; ET=essential thrombocythemia; HR=hazard ratio; MPN=myeloproliferative neoplasm; MPN-U=myeloproliferative neoplasm unclassifiable; PMF=primary myelofibrosis; PV=polycythemia vera; TEs=thrombotic events.
In the CYTO-PV study† of 365 patients with PV with elevated Hct between 45% and 50%
of cardiovascular death and major thrombosis in patients managed at an Hct target level of 45% to 50% vs Hct level managed to <45%3 (HR, 3.91; 95% CI, 1.45–10.53; P = 0.007)
†In the CYTO-PV study of 365 adult patients with PV treated with PBT, HU, or both, patients were randomized to 1 of 2 groups—either the low-Hct group (n = 182; with more intensive therapy to maintain a target Hct level <45%) or the high-Hct group (n = 183; with less intensive therapy to maintain a target Hct level of 45% to 50%). Baseline characteristics were balanced between the groups. Approximately 50% of patients had received an initial diagnosis of PV within 2 years prior to randomization. 67.1% of patients (n = 245) were at high risk because of age ≥65 years or previous thrombosis. The composite primary endpoint was the time until cardiovascular death or major thrombosis.3
CI=confidence interval; CYTO-PV=Cytoreductive Therapy in Polycythemia Vera; Hct=hematocrit; HR=hazard ratio; HU=hydroxyurea; PBT=phlebotomy; PV=polycythemia vera.
In an additional analysis† from the CYTO-PV study Elevated WBC counts >11 × 109/L increased the risk of thrombosis4
WBC ≥11 vs <7 x 109/L HR, 3.90; 95% CI, 1.24–12.3; P = 0.02
†In the CYTO-PV study of 365 adult patients with PV treated with PBT, HU, or both, patients were randomized to 1 of 2 groups—either the low-Hct group (n = 182; with more intensive therapy to maintain a target Hct level <45%) or the high-Hct group (n = 183; with less intensive therapy to maintain a target Hct level of 45% to 50%). Baseline characteristics were balanced between the groups. Approximately 50% of patients had received an initial diagnosis of PV within 2 years prior to randomization. 67.1% of patients (n = 245) were at high risk because of age ≥65 years or previous thrombosis. The composite primary endpoint was the time until cardiovascular death or major thrombosis.3
CI=confidence interval; CYTO-PV=Cytoreductive Therapy in Polycythemia Vera; Hct=hematocrit; HR=hazard ratio; WBC=white blood cell.
TEs are a major cause of mortality among patients with PV.8 In the REVEAL study,§ a prospective, observational study of 2510 patients with PV, of the 175 patients with known cause of death
33% of deaths
were due to thrombotic complications, the most common known cause of death8
§REVEAL was a prospective, observational study of 2510 adult patients with PV in the United States, sponsored by Incyte. Patients were enrolled over an approximate 2-year period (July 2014 to August 2016). This analysis included all enrolled patients and evaluated characteristics of deceased patients, survival by risk, and causes of death over the course of the study. A total of 244 patients died during the study, with 190 having elevated Hct values and WBC counts in the 6 months before death, and 175 having a known cause of death. Among the 244 patients who died during the study, 82% (n = 200) were categorized as high risk at diagnosis, primarily due to age ≥60 years only (65%; n = 159).8,10
Hct=hematocrit; PV=polycythemia vera; TEs=thrombotic events; WBC=white blood cell.
In a survey|| of 147 employed patients with MPNs, including 55 with PV
~1/3 of patients
with PV and a history of TEs required medical disability leave11
||The Living with MPNs patient survey was a cross-sectional online questionnaire of 904 MPN patients conducted from April to November 2016. Symptom burden and functional status were compared in patients who reported taking medical disability leave (MDL) due to their MPN vs patients who reported no changes in employment status. Among the 592 patients who were employed full- or part-time at diagnosis, 147 (24.8%) reported taking ≥1 MDL (MF, 37.9%; PV, 22.2%; ET, 15.3%) vs 293 (49.4%) who reported no change in employment status as a result of their MPN. Of the patients who took MDL, 29.9% took ≥2 MDLs, and most patients (62.6%) did not return to work.10 This is an Incyte-sponsored survey.
ET=essential thrombocythemia; MF=myelofibrosis; MPN=myeloproliferative neoplasm; PV=polycythemia vera; TEs=thrombotic events.
CONSIDER QualityInitiatives
IMPACT ON THE HEALTHCARE SYSTEM
A retrospective, cross-sectional analysis* of US healthcare resource utilization and costs for adult patients with PV and TEs demonstrated
Patients with TEs demand greater healthcare resources vs those without TEs12
3x
the cost of healthcare12
$45,040 mean total annual costs for patients with PV and TEs vs $16,438 for those without TEs (P < 0.001)
*Retrospective, cross-sectional database analysis including 1322 adult patients with a PV diagnosis who were newly treated with hydroxyurea and continuously enrolled in medical and pharmacy benefit plans for ≥12 months pre- and post-index. Healthcare resource utilization and costs were analyzed in a subgroup analysis comparing patients who had TEs in the 12-month follow-up period with those who did not.12
The same retrospective analysis* demonstrated that patients with PV and TEs had higher rates of inpatient healthcare resource utilization
50.9% (110/216) for those with TEs vs 18.4% (203/1106) for those without TEs (P < 0.001)
*Retrospective, cross-sectional database analysis including 1322 adult patients with a PV diagnosis who were newly treated with hydroxyurea and continuously enrolled in medical and pharmacy benefit plans for ≥12 months pre- and post-index. Healthcare resource utilization and costs were analyzed in a subgroup analysis comparing patients who had TEs in the 12-month follow-up period with those who did not.12
PV=polycythemia vera; TEs=thrombotic events.
The same retrospective analysis* further demonstrated that patients with PV and TEs had higher rates of outpatient healthcare resource utilization
48.2% (104/216) of patients with TEs vs 26.3% (291/1106) of patients without TEs (P < 0.001)
*Retrospective, cross-sectional database analysis including 1322 adult patients with a PV diagnosis who were newly treated with hydroxyurea and continuously enrolled in medical and pharmacy benefit plans for ≥12 months pre- and post-index. Healthcare resource utilization and costs were analyzed in a subgroup analysis comparing patients who had TEs in the 12-month follow-up period with those who did not.12
ER=emergency room; PV=polycythemia vera; TEs=thrombotic events.
CONSIDER QualityInitiatives
Recommended Monitoring
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommend Monitoring Patients With PV
The NCCN Guidelines® recommend monitoring patients with PV for new thrombosis or bleeding, response* to cytoreductive therapy, and signs and symptoms* of disease progression13
*Every 3-6 months or more frequently as clinically indicated.
Potential indications for change of cytoreductive therapy for patients with symptomatic low-risk PV or high-risk PV with no response or loss of response13
HU=hydroxyurea; NCCN=National Comprehensive Cancer Network; PV=polycythemia vera.
- Intolerance or resistance to HU or peginterferon alfa-2a
- Disease-related symptoms
- New thrombosis or disease-related major bleeding
- Progressive thrombocytosis and/or leukocytosis
- Frequent phlebotomy or intolerant of phlebotomy
- Splenomegaly
References: 1. Emanuel RM, Dueck AC, Geyer HL, et al. Myeloproliferative Neoplasm (MPN) Symptom Assessment Form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol. 2012;30(33):4098-4103. 2. Mesa R, Miller CB, Thyne M, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and productivity: the MPN Landmark survey. BMC Cancer. 2016;16:167. 3. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33. 4. Barbui T, Masciulli A, Marfisi MR, et al. White blood cell counts and thrombosis in polycythemia vera: a subanalysis of the CYTO-PV study. Blood. 2015;126(4):560-561. 5. Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27:1874-1881. 6. Tefferi A, Vannucchi AM, Barbui T. Polycythemia vera: historical oversights, diagnostic details, and therapeutic views. Leukemia. 2021;35:3339-3351. 7. Grunwald MR, Burke JM, Kuter DJ, et al. Symptom burden and blood counts in patients with polycythemia vera in the United States: an analysis from the REVEAL study. Clin Lymphoma Myeloma Leuk. 2019;19(9):579-584. 8. Stein B, Patel K, Scherber RM, et al. Mortality and causes of death of patients with polycythemia vera: analysis of the reveal prospective, observational study. Abstract #484. Presented at: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. 9. Hulcrantz M, Björkholm M, Dickman PW, et al. Risk of arterial and venous thrombosis in patients with myeloproliferative neoplasms: a population-based cohort study. Ann Intern Med. 2018;168(5):317-325. 10. Grunwald MR, Stein BL, Boccia RV, et al. Clinical and disease characteristics from REVEAL at time of enrollment (baseline): prospective observational study of patients with polycythemia vera in the United States. Clin Lymphoma Myeloma Leuk. 2018;18(12):788-795. 11. Yu J, Paranagama D, Geyer HL, et al. Relationship between symptom burden and disability leave among patients with myeloproliferative neoplasms (MPNs): findings from the Living with MPN patient survey. Ann Hematol. 2019;98(5):1119-1125. 12. Parasuraman S, DiBonaventura M, Reith K, et al. Patterns of hydroxyurea use and clinical outcomes among patients with polycythemia vera in real world clinical practice: a chart review. Exp Hematol Oncol. 2016;5:3. 13. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.1.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 6, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.