Treating polycythemia vera

Treatment goals

The primary aim of polycythemia vera (PV) management is to maintain HCT below the 45% threshold

This serves to reduce the risk of CV death and major thrombosis. Other treatment goals include reducing the burden of phlebotomy, symptom reduction, and delaying disease progression.3,15,24
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Even slight increases in HCT can increase TE risk

In the CYTO-PV study, people with PV who consistently maintained HCT levels ≥45%, even within 45%-50%, were 4x more likely to experience thrombosis and CV death compared to those whose HCT was tightly controlled below the 45% threshold.3*

*In an Italian RCT study (CYTO-PV) of 365 PV patients being treated with phlebotomy, hydroxyurea, or both, 2.7% (n=5/182) with HCT <45% died from CV causes or had major thrombotic events vs 9.8% (n=18/183) with HCT 45%-50% after a median follow-up of 31 months (HR, 3.91; 95% CI, 1.45-10.53; P=0.007).3

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78% of people with PV lack consistent HCT control (N=4,264)1,2

A retrospective analysis of 28,306 PV patients found that only 14% of low-risk and 25% of high-risk patients consistently maintained HCT below the 45% threshold, despite treatment with phlebotomy with or without cytoreductive therapy.1†

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Managing symptoms and minimizing overall disease burden are important given the chronic nature of the disease, with patients living a median of ~12 years after diagnosis, and more than 35 years after diagnosis for patients ≤40 years of age.11,15

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In an observational study, worsening symptoms affected 47% (n=133/285) of PV patients, of which the majority‡ were actively treated.4§

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Approximately 60% (n=23/38) of people with PV show laboratory evidence of iron depletion, including low serum iron, TSAT, and ferritin.5

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Even when HCT is controlled, iron deficiency may increase symptom burden in people with PV.3,5,7

†There are certain limitations of this study that are consistent with the retrospective nature of claims-based analyses and include the potential for incomplete or missing records and misdiagnosis of PV, as diagnoses were based solely on database records. There is also the possibility that thrombotic events were misdiagnosed, underdiagnosed, or otherwise, incorrectly reported.1

‡227 (79%) and 217 (76%) patients were actively receiving cytoreductive and antiplatelet therapy, respectively.4

§A multicenter, retrospective, observational study comprising patients from 13 academic and community centers. Eligibility criteria were patients >18 years old, enrolled with a diagnosis of PV, ET or MF (primary or post-PV/ET) according to WHO and/or International Consensus criteria, and having completed at least one MPN-SAF TSS questionnaire between April 2013 and August 2022.4

Treatment overview

Common treatments for PV include:

Therapeutic phlebotomy and low-dose aspirin
Therapeutic phlebotomy, used in combination with low-dose aspirin per ELN recommendations15,30,31
  • Aspirin is used to reduce the risk of thrombosis15,32
    • Aspirin belongs to the class of NSAIDs, and can help reduce thrombotic risk and alleviate microvascular symptoms by preventing platelet aggregation32
  • Therapeutic phlebotomy—in patients under 60 years of age with no prior thrombosis (low-risk PV), therapeutic phlebotomy is typically initiated as a treatment for temporary HCT reduction15,33,34
    • This treatment removes blood cells from the body, reducing blood viscosity and causing iron deficiency to limit red blood cell production35
    • Therapeutic phlebotomy is reactive and is often unpredictable, which may cause stress and anxiety6
    • People with PV require ~8 therapeutic phlebotomies per year, with each procedure lasting up to 4 hours6,36
      • Logistical challenges, such as finding a treatment site and frequency of clinic or hospital visits, interfere with daily life and productivity6,36
    • In addition to lowering total blood volume, a therapeutic phlebotomy induces temporary iron deficiency to curtail erythropoiesis37
    • Therapeutic phlebotomy exacerbates iron deficiency and PV symptom burden6
    • Iron deficiency persists or worsens with ongoing therapeutic phlebotomies—especially as erythrocytosis continues7,38
    • People receiving therapeutic phlebotomy tend to report more severe symptoms, including fatigue, which creates quality of life burdens33
      • 85.8% reported distress due to the procedure36‖
    • Patients may also become intolerant, and it may be difficult to gain access to the appropriate vein39

Cytoreductive therapy (CRT)
CRT (eg, hydroxyurea, interferons therapy, and JAK inhibitors) is recommended to reduce HCT for patients ≥60 years old, those with prior thrombosis, intolerance to phlebotomy, progressive splenomegaly, or persistent symptoms despite first-line care15
  • Hydroxyurea is an antimetabolite chemotherapy that interferes with cellular DNA synthesis and causes cell death40
    • It offers limited efficacy with significant side effects41
    • It is associated with resistance and intolerance, which occurs in 24% of patients42
  • JAK inhibitors work by downregulating JAK signal transduction and activation of transcription pathways to inhibit myeloproliferation43
  • Interferons work upstream of JAK mutations in the bone marrow44
    • They also require ~8 months to take effect, so patients may require close monitoring during this time45
  • All currently approved CRTs are associated with high rates of discontinuation due to adverse events, which occur in up to 37% of patients43,46,47

‖Based on a prospective, observational study of 2,510 PV patients receiving phlebotomy who were evaluated using a phlebotomy burden questionnaire.36

Symptoms & well-being

Empathy can be a powerful tool

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Among newly diagnosed MPN patients, people with PV report many quality of life deficits.48¶

Assessing mental and emotional well-being as a routine practice helps physicians understand each patient’s comprehensive experience of PV.6

The primary aim of the study was to investigate and compare the QoL at diagnosis in patients diagnosed with MPNs (ET [N=80], PV [N=73], primary MF [N=22], and MPN undifferentiated [N=4]), using EORTC QLQ-C30 and MPN-SAF. The EORTC QLQ-C30 is a cancer-specific questionnaire with 30 items that is composed of five functional scales, three symptom scales, a global QoL scale, and six single items, and the MPN-SAF is composed of 27 items.48

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62% of people with PV, even those with low calculated prognostic risk score, report that their symptoms reduced their quality of life (N=380).23

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Asking your patients open-ended questions is an essential strategy to better understand how PV, and its treatment, truly impacts their day-to-day life.24

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Phrases like “I’m tired,” “I’m off,” or “I’m not me,” are clues to disease burden that labs won’t catch.23,24

Get tips to guide deeper discussions with
your patients

CI=confidence interval; CRT=cytoreductive therapy; CV=cardiovascular; CYTO-PV=cytoreductive therapy in polycythemia vera; ELN=European LeukemiaNet; EORTC QLQ-C30=European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30; ET=essential thrombocythemia; HCT=hematocrit; HR=hazard ratio; JAK=Janus kinase; MF=myelofibrosis; MPN=myeloproliferative neoplasm; MPN-SAF=Myeloproliferative Neoplasm Symptom Assessment Form; NSAID=non-steroidal anti-inflammatory drug; PV=polycythemia vera; QoL=quality of life; RCT=randomized controlled trial; TE=thromboembolic event; TSAT=transferrin saturation; TSS=total symptom score; WHO=World Health Organization.

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References

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