The effect of interferon alpha on myeloproliferation and vascular complications in polycythemia vera

Heis, N.; Rintelen, Claudia; Gisslinger, Bettina; Knöbl, Paul; Lechner, Klaus; Gisslinger, Heinz

doi:10.1111/j.1600-0609.1999.tb01110.x

Cited by 28 publications

(7 citation statements)

References 18 publications

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“…Overall responses are 50% for reduction of HCT to less than 0.45% without concomitant phlebotomies, 77% for reduction in spleen size and 75% for reduction of pruritus. Results from single-institution studies with long-term follow-up are similar [ 21 , 22 ].…”

Section: Current Treatment Recommendations (Fig 1 mentioning

confidence: 95%

The treatment of polycythaemia vera: an update in the JAK2 era

Finazzi

Barbui

2007

Int Emergency Med

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The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases.

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Section: Current Treatment Recommendations (Fig 1 mentioning

confidence: 95%

The treatment of polycythaemia vera: an update in the JAK2 era

Finazzi

Barbui

2007

Int Emergency Med

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“…Subsequent studies have been conducted in PV; however, the majority of these trials included small numbers of patients with varying drug formulas and dosages and different response criteria, thus limiting the ability to summarize the results in a metaanalysis. Furthermore, the majority of these trials did not report the number of patients who discontinued IFN-a because of side effects [40][41][42][43][44][45][46][47][48][49][50]. Overall, approximately 47%-95% of the patients included in these trials had reduction in the number of phlebotomies, and 6%-85% required no phlebotomies during their treatment period [51].…”

Section: Interferonmentioning

confidence: 99%

Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

Nazha

Gerds

2016

The Oncologist

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The goals of therapy in patients with polycythemia vera (PV) are to improve disease‐related symptoms, prevent the incidence or recurrence of thrombosis, and possibly delay or prevent the transformation into myelofibrosis or acute myeloid leukemia (AML). Cytoreductive therapies have been used in older patients and those with a history of thrombosis to achieve these goals. Hydroxyurea (HU) remains the first‐line cytoreductive choice; however, up to one in four patients treated with HU over time will develop resistance or intolerance to HU. More importantly, patients who fail HU have a 5.6‐fold increase in mortality and a 6.8‐fold increase risk of transformation to myelofibrosis or AML; therefore, alternative therapies are needed for these patients. Interferon‐α has been used in PV and has shown significant activity in achieving hematologic responses and decreasing JAK2 V617F mutation allele burden. JAK inhibition has also been investigated and recently garnered regulatory approval for this indication. In this review, we will discuss the current treatment options that are available for patients after HU and the novel therapies that are currently under investigation. Implications for Practice: The outcomes of PV patients who fail or who are intolerant of hydroxyurea are poor. Although pegylated interferon can be considered in younger patients, currently, ruxolitinib is the only U.S. Food and Drug Administration‐approved agent in this setting, representing a viable option, leading to hematocrit control and a reduction in spleen size and constitutional symptoms. Although a small number of patients will achieve a molecular response with continuous treatment, the implications of such response on the clinical outcomes are still unknown. Patients whose disease is not adequately controlled with ruxolitinib, or who lose their response, can be treated with low‐dose busulfan or pipobroman; however, they should be encouraged to participate in trials with novel therapies.

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“…Since 1985, observational, nonrandomized studies have provided convincing evidence that interferon a (IFN-a) treatment of patients with MPNs including PV can effectively normalize blood cell counts and prevent disease-related thromboembolic complications. [1][2][3][4] Since the discovery of the gain-of-function mutation V617F of the JAK2 gene, [5][6][7][8] which is detectable in .95% of PV patients, monitoring of JAK2 V617F allelic load emerged as a suitable tool to demonstrate the anticlonal activity of IFN-a therapy. [9][10][11][12] This nonleukemogenic compound is therefore considered one of the most promising therapeutic tools for long-term treatment in PV, and is also used to treat other MPNs including essential thrombocythemia (ET) and early stages of primary myelofibrosis.…”

Section: Introductionmentioning

confidence: 99%

Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera

Gisslinger

Zagrijtschuk

Buxhofer‐Ausch

et al. 2015

Blood

158

143

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Key Points• The novel IFNa-2b, ropeginterferon alfa-2b, administered once every 2 weeks has low toxicity and induces high and sustained response rates in polycythemia vera patients.• Ropeginterferon alfa-2b induces significant partial and complete molecular response rates, as reflected by reduction of JAK2 allelic burden.In this prospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-pegylated interferon (IFN) a-2b isoform, ropeginterferon alfa-2b. The unique feature of ropeginterferon alfa-2b is a longer elimination half-life, which allows administration every 2 weeks. We present data from 51 polycythemia vera patients. The main goal was to define the maximum tolerated dose and to assess safety and efficacy. A dose range of 50 to 540 mg was tested without the appearance of dose-limiting toxicities. All drug-related adverse events were known toxicities associated with IFN-a. The cumulative overall response rate was 90%, comprising complete response in 47% and partial response in 43% of patients; the best individual molecular response level was a complete response in 21% of patients and partial response in 47%. Notably, we did not observe any correlation between the dose level and the response rate or response duration, suggesting that already low levels of ropeginterferon alfa-2b are sufficient to induce significant hematologic and molecular responses. These data suggest promising efficacy and safety of ropeginterferon alfa-2b and support the development of the drug in a randomized phase 3 clinical trial.

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The effect of interferon alpha on myeloproliferation and vascular complications in polycythemia vera

Cited by 28 publications

References 18 publications

The treatment of polycythaemia vera: an update in the JAK2 era

The treatment of polycythaemia vera: an update in the JAK2 era

Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera

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