A phase II trial of pegylated interferon α‐2b therapy for polycythemia vera and essential thrombocythemia

Abstract

BACKGROUNDConventional interferon‐α (IFN) is an effective treatment for patients with myeloproliferative disorders. However, many patients discontinue therapy because of side effects.METHODSIn this 24‐month, Phase II feasibility study of pegylated interferon α‐2b (PEG‐IFN) treatment, a starting dose of 0.5 μg/kg per week was received by 21 patients with polycythemia vera (PV) and 21 patients with essential thrombocythemia (ET). The treatment objective, a complete platelet response (CR), was a platelet count <400 × 109/L in symptomatic patients and <600 in asymptomatic patients. Neutrophil polycythemia rubra vera‐1 (PRV‐1) messenger RNA expression was analyzed prior to and during therapy. Quality of life (QoL) was investigated by using the European Organization for Research and Treatment of Cancer QLQ‐C30 questionnaire.RESULTSAt 6 months, 29 of 42 patients (69%) had achieved a CR after a median of 83 days. The CR rate was not related to diagnosis, gender, or previous therapy. Nineteen patients completed the planned 2‐year treatment in CR. No thromboembolic or bleeding complications were observed. Phlebotomy requirements were reduced in the majority of patients with PV. Five of 14 patients (36%) who initially were positive for PRV‐1 achieved normalized PRV‐1 expression under PEG‐IFN treatment. Side effects were the cause of therapy failure in 16 of 23 patients. However, only 8 of 19 patients reported any side effects at 2 years. The QLQ‐C30 revealed clinically significant impairments in several aspects of QoL at 6 months; however, at 2 years, QoL measurements were not different from baseline.CONCLUSIONSPEG‐IFN effectively reduced platelet counts in 29 of 42 patients, but only 19 patients maintained a CR at 2 years. The reversal of PRV‐1 positivity noted in a subset of patients suggested that PEG‐IFN may have an effect on the malignant clone. PEG‐IFN is a valuable therapeutic alternative for patients who tolerate its initial side effects. Cancer 2006. © 2006 American Cancer Society.

Long-term management of thrombocytosis in essential thrombocythaemia

“…the JAK2V617F allele burden) [83][84][85]. The biological and clinical significance of these results are unclear, and larger-scale studies are required to confirm the original findings.…”

“…fever higher than 38°C) lasted a maximum of 4-8 days following treatment initiation [87]. Despite this abatement, dropout rates between 15% and 66% have been reported, most commonly around 25% [88][89][90].…”

“…Such chemical modification increases serum half-life and reduces renal excretion, thus allowing weekly, rather than daily, administration. Pegylated-interferon-α has been shown to effectively control platelet count and disease symptoms in patients with MPDs, including ET [88,[100][101][102]. However, in two studies of 38 and 42 patients with an MPD, pegylatedinterferon-α had a similar tolerability profile to conventional interferon-α, with 26% and 50% of patients stopping therapy due to side effects and the level of toxicity limiting the duration of therapy [101,102].…”

Safety and efficacy of combination therapy of interferon‐α2 and ruxolitinib in polycythemia vera and myelofibrosis

“…Pegylated forms of IFNα2 (PEG‐IFNα2) allow administration once weekly and have proven efficacious in ET9, 10, 11, 12 and PV9, 10, 11, 12, 13, 14, 15. Patients in the early phase of MF, defined by low‐ or intermediate‐risk disease on the Dynamic International Prognostic Scoring System (DIPSS) scale,16 have also been shown to benefit from treatment with IFNα2 9, 17, 18.…”

“…Of note, in a subset of patients, long‐term treatment with IFNα2 induces deep molecular remission sustained even years after cessation of therapy 9, 10, 11, 13, 14, 15. However, the use of IFNα2 is limited by toxicity with an average discontinuation rate of 10‐30% 10, 12, 19. Moreover, in a subset of MPN patients molecular responses are absent, which is in part attributed to additional non‐driver mutations and, possibly, concurrent inflammation and oxidative stress 10, 20…”