Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria.
Department of Internal Medicine I with Hematology, Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz GmbH Elisabethinen, Linz, Austria.
Hematol Oncol. 2020 Dec;38(5):792-798. doi: 10.1002/hon.2786. Epub 2020 Aug 19.
The goal of current management of patients with chronic phase chronic myeloid leukemia (CML) is to reach treatment-free remission with sustained deep molecular remission (DMR) being the prerequisite therefor. Second-generation tyrosine kinase inhibitors can induce deeper and faster remission than imatinib, but are often associated with severe adverse events (AEs). The combination of pegylated interferon (IFN) with imatinib was shown to induce higher molecular remissions than imatinib alone in two studies. Treatment discontinuation rates due to IFN induced AEs were high in both studies. To investigate safety, tolerability (primary objective), and efficacy (secondary objective) of the combination of imatinib with ropeginterferon alpha-2b this phase I study was initiated. Twelve patients were planned to be enrolled. Nine patients completed the study according to protocol. Three patients terminated the study early, one due to occurrence of a dose-limiting toxicity (neutropenia grade 3), one due to an AE (panic attacks grade 2) and one due to the patient's decision. Tolerability was good, non-hematologic AEs were mainly grade 1/2, hematologic AEs were mainly neutropenias. No new AEs were reported for the combination of imatinib and ropeginterferon alpha-2b. In a nondose-dependent manner the addition of ropeginterferon alpha-2b led to the achievement of a DMR in four out of nine patients after a treatment duration of 18 months. The combination of imatinib and ropeginterferon alpha-2b is safe and showed in this phase I study the ability to deepen the molecular response in patients with chronic phase CML not achieving a DMR with imatinib alone.
目前慢性期慢性髓性白血病（CML）患者的治疗目标是实现无治疗缓解，持续深度分子缓解（DMR）是其前提。第二代酪氨酸激酶抑制剂（TKI）可比伊马替尼诱导更深、更快的缓解，但常伴有严重不良反应（AE）。两项研究表明，聚乙二醇干扰素（IFN）联合伊马替尼比单用伊马替尼诱导更高的分子缓解。两项研究中因 IFN 相关 AE 导致停药的发生率均较高。为了研究伊马替尼联合罗哌干扰素α-2b 的安全性、耐受性（主要目标）和疗效（次要目标），启动了这项 I 期研究。计划入组 12 例患者。9 例患者按方案完成了研究。3 例患者提前退出研究，1 例因剂量限制性毒性（中性粒细胞减少症 3 级），1 例因 AE（惊恐发作 2 级），1 例因患者决定。耐受性良好，非血液学 AE 主要为 1/2 级，血液学 AE 主要为中性粒细胞减少症。伊马替尼联合罗哌干扰素α-2b 无新的 AE 报告。在 18 个月的治疗后，罗哌干扰素α-2b 的加入以非剂量依赖性方式使 9 例患者中的 4 例达到了 DMR。伊马替尼联合罗哌干扰素α-2b 是安全的，在这项 I 期研究中显示了能够加深对单用伊马替尼未达到 DMR 的慢性期 CML 患者的分子反应。
