Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera
Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera
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DOI：
10.1182/blood-2008-03-143537
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发表时间：
2008-10-15
期刊：
影响因子：
20.3
通讯作者：
Fenaux, Pierre
中科院分区：
文献类型：
--
作者：
Kiladjian, Jean-Jacques;Cassinat, Bruno;Fenaux, Pierre
干扰素-α（IFN-α）是一种非致白血病的治疗真性红细胞增多症（PV）能够诱导细胞遗传学缓解。它的使用受到毒性的限制，导致大约20%的患者停止治疗。我们在40例PV患者中完成了聚乙二醇化IFN-α-2a的2期多中心研究。目的包括使用JAK 2 V617 F定量（%V617F）评价疗效、安全性和监测残留疾病。中位随访时间为31.4个月。12个月时，所有37例可评价患者均出现血液学缓解，包括94.6%的完全缓解（CR）。仅3例患者（8%）停止治疗。第一年后，35例患者保持血液学CR，包括5例停用聚乙二醇IFN-α-2a的患者。29例患者的%V617F监测序贯样本显示，26例（89.6%）患者的%V617F降低。中位%V617F从聚乙二醇化IFN-α-2a之前的45%分别降低至12、18、24和36个月后的22.5%、17.5%、5%和3%。7例患者达到分子CR（JAK 2 V617 F检测不到），持续6（+）至18（+）个月，5例患者在聚乙二醇化IFN-α-2a停药后持续存在。未记录血管事件。这些结果表明，聚乙二醇化IFN-α-2a在PV中产生高比率的血液学和分子学应答，具有有限的毒性，并且在选定的病例中甚至可以消除JAK 2突变克隆。可在www.clinicaltrials.gov上以#NCT00241241获得。
Interferon-alpha (IFN-alpha) is a nonleukemogenic treatment of polycythemia vera (PV) able to induce cytogenetic remissions. Its use is limited by toxicity, leading to treatment discontinuation in approximately 20% of patients. We completed a phase 2 multicenter study of pegylated IFN-alpha-2a in 40 PV patients. Objectives included evaluation of efficacy, safety, and monitoring of residual disease using JAK2V617F quantification (%V617F). Median follow-up was 31.4 months. At 12 months, all 37 evaluable patients had hematologic response, including 94.6% complete responses (CRs). Only 3 patients (8%) had stopped treatment. After the first year, 35 patients remained in hematologic CR, including 5 who had stopped pegylated IFN-alpha-2a. Sequential samples for %V617F monitoring, available in 29 patients, showed %V617F decrease in 26 (89.6%). Median %V617F decreased from 45% before pegylated IFN-alpha-2a to 22.5%, 17.5%, 5%, and 3% after 12, 18, 24, and 36 months, respectively. Molecular CR (JAK2V617F undetectable) was achieved in 7 patients, lasting from 6(+) to 18(+) months, and persisted after pegylated IFN-alpha-2a discontinuation in 5. No vascular event was recorded. These results show that pegylated IFN-alpha-2a yields high rates of hematologic and molecular response in PV with limited toxicity, and could even eliminate the JAK2 mutated clone in selected cases. Available at www.clinicaltrials.gov as #NCT00241241.