Them Nicole C C, Bagienski Klaudia, Berg Tiina, Gisslinger Bettina, Schalling Martin, Chen Doris, Buxhofer-Ausch Veronika, Thaler Josef, Schloegl Ernst, Gastl Guenther A, Wolf Dominik, Strecker Karin, Egle Alexander, Melchardt Thomas, Burgstaller Sonja, Willenbacher Ella, Zagrijtschuk Oleh, Klade Christoph, Greil Richard, Gisslinger Heinz, Kralovics Robert
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Am J Hematol. 2015 Apr;90(4):288-94. doi: 10.1002/ajh.23928. Epub 2015 Mar 2.
Fifty-one polycythemia vera (PV) patients were enrolled in the phase I/II clinical study PEGINVERA to receive a new formulation of pegylated interferon alpha (peg-proline-IFNα-2b, AOP2014/P1101). Peg-proline-IFNα-2b treatment led to high response rates on both hematologic and molecular levels. Hematologic and molecular responses were achieved for 46 and 18 patients (90 and 35% of the whole cohort), respectively. Although interferon alpha (IFNα) is known to be an effective antineoplastic therapy for a long time, it is currently not well understood which genetic alterations influence therapeutic outcomes. Apart from somatic changes in specific genes, large chromosomal aberrations could impact responses to IFNα. Therefore, we evaluated the interplay of cytogenetic changes and IFNα responses in the PEGINVERA cohort. We performed high-resolution SNP microarrays to analyze chromosomal aberrations prior and during peg-proline-IFNα-2b therapy. Similar numbers and types of chromosomal aberrations in responding and non-responding patients were observed, suggesting that peg-proline-IFNα-2b responses are achieved independently of chromosomal aberrations. Furthermore, complete cytogenetic remissions were accomplished in three patients, of which two showed more than one chromosomal aberration. These results imply that peg-proline-IFNα-2b therapy is an effective drug for PV patients, possibly including patients with complex cytogenetic changes.
51例真性红细胞增多症（PV）患者参加了I/II期临床研究PEGINVERA，以接受聚乙二醇化干扰素α的新制剂（聚脯氨酸-干扰素α-2b，AOP2014/P1101）。聚脯氨酸-干扰素α-2b治疗在血液学和分子水平上均产生了高缓解率。分别有46例和18例患者（占整个队列的90%和35%）实现了血液学和分子学缓解。尽管干扰素α（IFNα）长期以来一直被认为是一种有效的抗肿瘤疗法，但目前尚不清楚哪些基因改变会影响治疗结果。除了特定基因的体细胞变化外，大的染色体畸变也可能影响对IFNα的反应。因此，我们在PEGINVERA队列中评估了细胞遗传学变化与IFNα反应之间的相互作用。我们进行了高分辨率SNP微阵列分析，以检测聚脯氨酸-干扰素α-2b治疗前和治疗期间的染色体畸变。在有反应和无反应的患者中观察到相似数量和类型的染色体畸变，这表明聚脯氨酸-干扰素α-2b的反应独立于染色体畸变而实现。此外，3例患者实现了完全细胞遗传学缓解，其中2例显示有不止一种染色体畸变。这些结果表明，聚脯氨酸-干扰素α-2b治疗对PV患者是一种有效的药物，可能包括细胞遗传学变化复杂的患者。
