Prediction of sustained remission after tyrosine kinase inhibitor discontinuation with BCR::ABL1 digital PCR in chronic myeloid leukemia patients

IF 2.3 3区 医学 Q2 HEMATOLOGY European Journal of Haematology Pub Date : 2024-07-12 DOI:10.1111/ejh.14271
Camille Kockerols, Peter J. M. Valk, Jeroen J. W. M. Janssen, Pauline Hogenbirk, Jan J. Cornelissen, Susanne Saussele, Birgit Spiess, Maria Agustina Perusini, Dennis Kim, Peter E. Westerweel
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Abstract

Precise and reliable predictive parameters to accurately identify chronic myeloid leukemia (CML) patients who can successfully discontinue their tyrosine kinase inhibitor (TKI) treatment are lacking. One promising parameter is depth of molecular response measured by BCR::ABL1 digital PCR (dPCR). The aim of this study was to validate a previously described prediction cutoff of 0.0023%IS and to assess the value of dPCR for treatment-free remission (TFR) prediction in relation to other clinical parameters. A droplet-based dPCR assay assessed BCR::ABL1 %IS prior to TKI discontinuation. The primary endpoint was molecular recurrence (MolR) by 36 months. A total of 186 patients from Canada, Germany, and the Netherlands were included. In patients with a first TKI discontinuation attempt (n = 163), a BCR::ABL1 dPCR < and ≥0.0023%IS had a MolR probability of 33% and 70%, respectively. Patients treated less than 6 years with a BCR::ABL1 dPCR <0.0023%IS had a MolR probability of 31%. After correction for treatment duration, both high dPCR value and the use of imatinib (vs. second-generation TKI) were significantly associated with a higher risk of MolR (HR of 3.66, 95%CI 2.06–6.51, p < .001; and 2.85, 95%CI 1.25–6.46, p = .013, respectively). BCR::ABL1 dPCR was not associated with TFR outcome after second TKI discontinuation, however, with the limitation of a small number of patients analyzed (n = 23). In conclusion, BCR::ABL1 digital PCR based on the cutoff of 0.0023%IS is a valuable predictive tool to identify CML patients with a high probability of TFR success after first TKI discontinuation, including patients treated for less than 6 years.

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利用 BCR::ABL1 数字 PCR 预测慢性髓性白血病患者停用酪氨酸激酶抑制剂后的持续缓解。
目前还缺乏准确可靠的预测参数来准确识别可以成功中止酪氨酸激酶抑制剂(TKI)治疗的慢性髓性白血病(CML)患者。一个很有前景的参数是通过 BCR::ABL1 数字 PCR (dPCR) 测量的分子反应深度。本研究旨在验证之前描述的 0.0023%IS 预测临界值,并评估 dPCR 与其他临床参数相关的无治疗缓解 (TFR) 预测价值。基于液滴的 dPCR 检测评估了 TKI 停药前的 BCR::ABL1 %IS。主要终点是36个月前的分子复发(MolR)。共纳入了来自加拿大、德国和荷兰的 186 名患者。在首次尝试停用TKI的患者(n = 163)中,BCR::ABL1 dPCR<和≥0.0023%IS的MolR概率分别为33%和70%。治疗时间少于 6 年、BCR::ABL1 dPCR IS 的患者的 MolR 概率为 31%。校正治疗时间后,高 dPCR 值和使用伊马替尼(与第二代 TKI 相比)与较高的 MolR 风险显著相关(HR 为 3.66,95%CI 为 2.06-6.51,p IS 是一种有价值的预测工具,可用于识别首次停用 TKI 后 TFR 成功概率较高的 CML 患者,包括治疗时间不足 6 年的患者。
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来源期刊
CiteScore
5.50
自引率
0.00%
发文量
168
审稿时长
4-8 weeks
期刊介绍: European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
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