Hematology Research Unit Helsinki, Department of Medicine, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Eur J Haematol. 2014;92(5):413-20. doi: 10.1111/ejh.12258. Epub 2014 Jan 28.
Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-α2b) and imatinib may increase the rate of successful discontinuation.
In this pilot study, we prospectively stopped imatinib from patients (n = 12) who had achieved major molecular response (MMR) after ≥12 months of treatment with either imatinib or imatinib+Peg-IFN-α2b. Molecular monitoring was carried out monthly for BCR-ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed.
In the monotherapy group, 5/6 patients lost MMR within 4 months. One patient remains to date in MR(4.0) 61 months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4 months while still receiving Peg-IFN-α2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3 months. One patient is still in sustained MR(4.0) at 58 months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells.
A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2 yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies.
先前的研究表明，在长时间完全分子缓解的慢性髓性白血病患者中，有 40-50%可能在没有即将复发的情况下停止伊马替尼治疗。聚乙二醇干扰素-α（Peg-IFN-α2b）和伊马替尼的联合使用可能会提高停药成功率。
在这项初步研究中，我们前瞻性地停止了接受伊马替尼或伊马替尼+Peg-IFN-α2b 治疗至少 12 个月后达到主要分子反应（MMR）的患者（n=12）的伊马替尼治疗。每月进行 BCR-ABL1 的分子监测。此外，还进行了淋巴细胞免疫表型、功能和血浆细胞因子分析。
在单药组中，5/6 例患者在 4 个月内失去 MMR。1 例患者在停药后 61 个月仍处于 MR(4.0)。在联合治疗组中，2/6 例患者在继续接受 Peg-IFN-α2b 治疗的 4 个月内复发。6 例中有 4 例能够同时停用两种治疗，但其中 3 例在停药后 3 个月复发。1 例患者在停药所有治疗后 58 个月仍处于持续的 MR(4.0)。所有复发患者均对伊马替尼重新有反应。两名成功停药的患者要么 NK 细胞数量增加，要么 T 细胞功能活跃。
与其他研究相比，我们研究中复发患者的频率更高可能是由于停药前伊马替尼治疗的持续时间较短。然而，在免疫系统活跃的选定患者中，即使 TKI 治疗持续时间较短（<2 年），也可能允许停药，但这需要在更大的前瞻性研究中得到证实。
