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Ruxolitinib for the prevention of thrombosis in polycythemia vera: a systematic review and meta-analysis.

ABSTRACT: Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea; however, evidence regarding its efficacy in terms of thrombosis reduction is uncertain. We searched Medline, Embase, and archives of abstracts from the European Hematology Association and the American Society of Hematology annual congresses from 2014 onward for randomized controlled trials comparing the treatment vs best available therapy (BAT). Our search retrieved 80 records; after screening of abstracts and full text, the total was reduced to 16. Evidence came from 4 randomized controlled trials, including 663 patients (1057 patients per year). We estimated a thrombosis risk ratio of 0.56 for ruxolitinib BAT, corresponding to an incidence of 3.09% and 5.51% patients per year, respectively. The number of thrombotic events reported with ruxolitinib was consistently lower than that with BAT in our sample, but, globally, the difference did not reach significance (P = .098). Hard evidence in favor of ruxolitinib is lacking; a clinical trial on selected patients at high risk of thrombosis would be warranted, but its feasibility is questionable.

SUBMITTER: Masciulli A

PROVIDER: S-EPMC6988397 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Ruxolitinib for the prevention of thrombosis in polycythemia vera: a systematic review and meta-analysis.

Masciulli Arianna A Ferrari Alberto A Carobbio Alessandra A Ghirardi Arianna A Barbui Tiziano T

Blood advances 20200101 2

Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea; however, evidence regarding its efficacy in terms of thrombosis reduction is uncertain. We searched Medline, Embase, and archives of abstracts from the European Hematology Association and the American Society of Hematology annual congresses from 2014 onward for randomized controlled trials comparing the treatment vs best availab ...[more]

PMID: 31985808

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Project description:Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea.We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging.The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard-therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy.In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera. (Funded by Incyte and others; RESPONSE ClinicalTrials.gov number, NCT01243944.).

Project description:Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis and the presence of Janus kinase (JAK) 2V617F or similar mutations. This review summarizes the pathophysiology of PV, the challenges associated with traditional treatment options, and the scientific rationale and supportive clinical evidence for targeted therapy with ruxolitinib. Accumulating evidence indicates that activating mutations in JAK2 drive the PV disease state. Traditional PV treatment strategies, including aspirin, phlebotomy, and cytoreduc-tive agents such as hydroxyurea, provide clinical benefits for some but not all patients and may not adequately treat PV-related symptoms. Furthermore, traditional treatment approaches are associated with potential side effects that may limit their usage and lead some patients to discon-tinue the treatment. Ruxolitinib is an orally available small-molecule tyrosine kinase inhibitor that is a potent and selective inhibitor of JAK1/JAK2. Ruxolitinib is approved in the US for patients with PV with an inadequate response or intolerance to hydroxyurea and in Europe for adults with PV who are resistant to or intolerant of hydroxyurea. In the Phase III RESPONSE registration trial, ruxolitinib was superior to the best available therapy in patients with PV who were resistant to or intolerant of hydroxyurea in controlling hematocrit levels, reducing spleen volume, and improving PV-related symptoms and quality-of-life measures. The most common nonhematologic adverse events in ruxolitinib-treated patients were headache, diarrhea, pruritus, and fatigue in the RESPONSE trial; hematologic adverse events were primarily grade 1 or 2. In the Phase IIIb nonregistration RELIEF trial, there were nonsignificant trends toward an improved symptom control in patients with PV on a stable hydroxyurea dose who were generally well controlled but reported disease-associated symptoms and switched to ruxolitinib vs those who continued hydroxyurea therapy. Updated treatment guidelines will be important for educating physicians about the role of ruxolitinib in the treatment of patients with PV.

Dataset Information

Ruxolitinib for the prevention of thrombosis in polycythemia vera: a systematic review and meta-analysis.

Publications

Ruxolitinib for the prevention of thrombosis in polycythemia vera: a systematic review and meta-analysis.

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