Kiladjian Jean-Jacques, Cassinat Bruno, Chevret Sylvie, Turlure Pascal, Cambier Nathalie, Roussel Murielle, Bellucci Sylvia, Grandchamp Bernard, Chomienne Christine, Fenaux Pierre
Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Service d'Hématologie Clinique and Paris 13 University, Bobigny, France.
Blood. 2008 Oct 15;112(8):3065-72. doi: 10.1182/blood-2008-03-143537. Epub 2008 Jul 23.
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.
干扰素-α（IFN-α）是真性红细胞增多症（PV）的一种非致白血病治疗方法，能够诱导细胞遗传学缓解。其应用因毒性而受限，约20%的患者会因此停药。我们完成了一项针对40例PV患者的聚乙二醇化干扰素-α-2a的2期多中心研究。目标包括使用JAK2V617F定量（%V617F）评估疗效、安全性以及监测残留疾病。中位随访时间为31.4个月。在12个月时，所有37例可评估患者均有血液学反应，其中94.6%为完全缓解（CR）。仅有3例患者（8%）停药。第一年之后，35例患者维持血液学CR，其中5例已停用聚乙二醇化干扰素-α-2a。29例患者有用于%V617F监测的序贯样本，26例（89.6%）显示%V617F下降。%V617F中位数从聚乙二醇化干扰素-α-2a治疗前的45%分别降至12、18、24和36个月后的22.5%、17.5%、5%和3%。7例患者实现了分子学缓解（JAK2V617F检测不到），持续6（+）至18（+）个月，5例在停用聚乙二醇化干扰素-α-2a后仍持续缓解。未记录到血管事件。这些结果表明，聚乙二醇化干扰素-α-2a在PV中产生高比率的血液学和分子学反应，且毒性有限，甚至在某些病例中可消除JAK2突变克隆。可在www.clinicaltrials.gov上获取，编号为#NCT00241241。
