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Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. | LitMetric

AI Article Synopsis

Article Abstract

Background: Pegylated interferon alfa-2a is an immunomodulatory agent used to treat polycythemia vera. The durability of responses and long-term safety of this drug in patients with polycythaemia vera and essential thrombocythaemia have not been reported. Here, we present long-term efficacy and safety data from a single-centre, open-label, phase 2 trial, after a median of 83 months follow up.

Methods: Patients older than 18 years who were diagnosed with essential thrombocythaemia or polycythaemia vera according to 2001 WHO criteria were eligible to enrol in our study. The initial starting dose of pegylated interferon alfa-2a was 450 μg subcutaneously once per week, but was decreased in a stepwise manner due to toxic effects to a final starting dose of 90 mg per week: three patients were started at a dose of 450 mg per week, three at 360 mg per week, 19 at 270 mg per week, 26 at 180 mg per week, and 32 at 90 mg per week. Treatment was continued for as long as the patients derived clinical benefit with reductions in dose and frequency of administration allowed at the discretion of the treating physician. Haematological responses were assessed every 3-6 months on the basis of blood counts as defined by the European LeukemiaNet critieria. The primary endpoint of the initial study was the proportion of patients with a haematological response. Complete haematological response was defined as normalisation of blood counts (for patients with essential thrombocythaemia, platelets ≤440 × 10 per L; for patients with polycythaemia vera, haemoglobin <15·0 g/L without phlebotomy) with complete resolution of palpable splenomegaly or symptoms in the absence of a thrombotic event. Data were analysed with descriptive statistics and in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00452023 and is ongoing but not enrolling new patients.

Findings: Between May 21, 2005, and Dec 1, 2015, patients were followed up for a median of 83 months (IQR 69-94 months). Pegylated interferon alfa-2a induced haematological (66 [80%] of 83 patients) and molecular responses (35 [63%] of 55 patients) in 40 patients with essential thrombocythaemia and 43 patients with polycythaemia vera, with median durations of 66 months (IQR 35-83) and 53 months (24-70), respectively. 26 (39%) of 66 haematological responders and 25 (71%) of 35 molecular responders (with the JAK2 Val617Phe mutation) have maintained some response during follow-up: 49% maintained their best molecular response (nine of ten patients who had a complete response, five of 20 who had a partial response, and three of five who had a minor response). The incidence of major venous-thrombotic events during the study was 1·22 per 100 person-years. Overall, 18 (22%) of 83 patients discontinued therapy due to treatment-related toxicity. Although toxicity rates decreased over time, five patients had treatment-limiting grade 3 or 4 toxicities after 60 months on therapy. 32 patients are still enrolled on the study.

Interpretation: Pegylated interferon alfa-2a can induce durable haematological and molecular responses in patients with essential thrombocythaemia and polycythaemia vera. This drug alone and in combination with other drugs could be explored further in clinical trials.

Funding: US National Cancer Institute.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421384PMC
http://dx.doi.org/10.1016/S2352-3026(17)30030-3DOI Listing

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