Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease

Geyer, Holly; Scherber, Robyn M.; Kosiorek, Heidi E.; Dueck, Amylou C.; Kiladjian, Jean‐Jacques; Xiao, Zhijian; Slot, Stefanie; Zweegman, Sonja; Sackmann, Federico; Fuentes, Ana Kerguelen; Hernández‐Maraver, Dolores; Döhner, Konstanze; Harrison, Claire; Radia, Deepti; Muxí, Pablo; Besses, Carlos; Cervantes, Francisco; Johansson, Peter; Andréasson, Björn; Rambaldi, Alessandro; Barbui, Tiziano; Bonatz, Karin; Reiter, Andreas; Boyer, Françoise; Étienne, Gabriel; Ianotto, Jean‐Christophe; Ranta, Dana; Roy, Lydia; Cahn, Jean Yves; Maldonado, Norman; Barosi, Giovanni; Ferrari, Maria Luisa; Gale, Robert Peter; Birgegård, Gunnar; Xu, Zefeng; Zhang, Yue; Sun, Xiujuan; Xu, Junqiang; Zhang, Peihong; Boekhorst, Peter te; Commandeur, Suzan; Schouten, Harry C.; Pahl, Heike L.; Grießhammer, Martin; Stegelmann, Frank; Lehmann, Thomas; Senyak, Zhenya; Vannucchi, Alessandro M.; Passamonti, Francesco; Samuelsson, Jan; Mesa, Ruben A.

doi:10.1200/jco.2015.62.9337

Cited by 56 publications

(37 citation statements)

References 15 publications

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“…The reason for this finding is unclear. Although compliance in a clinical trial may be better than in clinical practice, this is an unlikely explanation because previous findings in patients with PV suggest that HC treatment is not associated with clinically relevant improvements in symptoms (Johansson et al , 2012; Scherber et al , 2012; Mesa et al , 2015; Geyer et al , 2016). However, randomized controlled trial data addressing this question are lacking.…”

Section: Discussionmentioning

confidence: 96%

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF)

et al. 2016

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SummaryThe randomized, double‐blind, double‐dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV‐related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster (TSS‐C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib‐ and hydroxycarbamide‐treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82–4·04; P = 0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS‐C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P = 0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV‐related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement.

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Section: Discussionmentioning

confidence: 96%

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF)

et al. 2016

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“…Presence of splenomegaly, use of hydroxyurea, and phlebotomy requirement are all independently associated with a substantial symptom burden. 67 Interestingly, a high symptomatic burden may occur independently of conventional risk categories; therefore, some low-risk patients might remain under-managed according to current recommendations. 67 Another component of the PV-associated burden is the high incidence of co-existing hematologic or solid cancers.…”

Section: Recognizing the Burden Associated With Diseasementioning

confidence: 99%

“…67 Interestingly, a high symptomatic burden may occur independently of conventional risk categories; therefore, some low-risk patients might remain under-managed according to current recommendations. 67 Another component of the PV-associated burden is the high incidence of co-existing hematologic or solid cancers. In a study including 353 PV patients, a 3.44-fold increased risk of lymphoproliferative neoplasms, especially chronic lymphocytic leukemia, compared with the general population, was reported.…”

Section: Recognizing the Burden Associated With Diseasementioning

confidence: 99%

“…Furthermore, it was shown that patients with phlebotomy requirements present a substantial symptomatic burden. 67 Just based on the ELN criteria, need of (any) phlebotomy after three months on an optimal dose of hydroxyurea would per se be evidence of resistance to treatment, and therefore of an inadequately controlled disease. 92 However, there is no hard evidence that this concept might be translated into the clinical practice.…”

Section: Who Is the "Patient In Need Of Treatment"?mentioning

confidence: 99%

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From leeches to personalized medicine: evolving concepts in the management of polycythemia vera

Vannucchi

2016

Haematologica

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© Ferrata Storti Foundationing to the level of knowledge we have now. Table 1 lists some of these landmark studies; due to space constraints, I will not be able to address all of them in detail. Evolving concepts in diagnosis Making a diagnosis of polycythemia veraThe World Health Organization (WHO) recently released a revised classification of MPN in which important changes to the 2008 version were introduced (Table 2). 8 In the 2008 version, the most compelling innovation had been the introduction of JAK2V617F and "similar" mutations (involving JAK2 exon 12 in 3%-4% of patients) as major diagnostic criteria.3-6 Although JAK2V617F mutation is associated with PV in more than 95% of cases, it does not represent a clear diagnosis since it is found also in 50%-60% of ET and PMF. However, the use of JAK2V617F as a marker of clonal myeloproliferation greatly facilitates the distinction of PV from reactive or congenital erythrocytosis.Considering that isotope-based assays for measuring red cell mass (RCM) and plasma volume are not routinely available even in most tertiary centers, the 2008 WHO classification listed a hemoglobin level more than 185 g/L and 165 g/L in men and women, respectively, as a strong surrogate marker of absolute increase of RCM. Since some PV patients do not fulfill such high levels, other criteria were added to facilitate diagnosis, including: 1) hemoglobin or hematocrit level that is more than 99 th percentile of reference range for age, sex, or altitude of residence; 2) an RCM that is more than 25% above mean normal predicted value;3) a hemoglobin level more than 170 g/L and 150 g/L in men and women, associated with a sustained increase of 20 g/L from baseline not attributable to correction of iron deficiency. According to the pragmatic British standards, hematocrit more than 52% in males and more than 48% in females, or an RCM more than 25% above predicted value, are sufficient to establish a diagnosis of PV if JAK2 mutation is present. 9 However, a reassessment of how far the WHO criteria can be applied in a real-life setting raised the issue of JAK2V617F mutated patients with only a borderline increase in hemoglobin. It was shown that BM morphology, according to WHO guidelines, accurately reflected a condition of increased RCM, since all patients with increased RCM also had a BM morphology consistent with PV.

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“…In a retrospective analysis of patients with PV ( n = 538), hydroxyurea, IFN-α, aspirin, and/or phlebotomy were not associated with significant improvement in patient-reported symptom severity. Furthermore, in a prospective analysis, patients with PV ( n = 1,334) treated with phlebotomy and/or hydroxyurea continued to experience more severe symptoms compared with untreated patients [23] . Considered together, these findings emphasize an unmet treatment need for some patients with PV.…”

Section: Risk Factors and Traditional Treatment Optionsmentioning

confidence: 99%

Polycythemia Vera Management and Challenges in the Community Health Setting

Gerds

Dao

2017

Oncology

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Patients with polycythemia vera (PV) experience shortened survival, increased risk of thromboembolic and hemorrhagic events, and burdensome symptoms. For all patients with PV, treatment with aspirin and hematocrit control with phlebotomy are recommended. In addition, patients with high-risk status or poor hematocrit control benefit from cytoreductive therapy with hydroxyurea, although approximately 1 in 4 patients develops resistance or intolerance. For patients who are resistant to or intolerant of hydroxyurea, studies have shown that ruxolitinib, a Janus kinase 1/2 inhibitor, provides hematocrit control, reduces spleen size, normalizes blood counts, and improves PV-related symptoms. For many patients, PV is managed in a community health setting, and it is important that community hematologists, oncologists, and internists are familiar with the contemporary management of PV to improve patient outcomes, including management for patients who present with unique health-care needs. This review provides an overview of current treatment options for patients with PV and discusses challenging circumstances encountered by community providers in the management of PV, including symptom assessment, identification of hydroxyurea resistance/intolerance, pregnancy, elective surgeries, concomitant immunosuppressants, and managing patients in areas with limited access to specialized hematologic care.

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Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease

Cited by 56 publications

References 15 publications

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF)

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF)

From leeches to personalized medicine: evolving concepts in the management of polycythemia vera

Polycythemia Vera Management and Challenges in the Community Health Setting

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