Park Hyunkyung, Kim Hyeong-Joon, Sohn Sang-Kyun, Baik Yoonsuk, Kim Dongho, Lee Sung-Yeoun, Kong Jee Hyun, Kim Hawk, Shin Dong-Yeop, Ahn Jae-Sook, Park Jinny, Park Seonyang, Kim Inho
Department of Internal Medicine, Seoul National University-Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea.
Department of Internal Medicine, Chonnam National University, Hwasun Hospital, Hwasun, South Korea.
Ther Adv Hematol. 2023 Nov 2;14:20406207231205637. doi: 10.1177/20406207231205637. eCollection 2023.
Droplet digital polymerase chain reaction (ddPCR) is an exact method of measurement.
We conducted this study to identify the prognostic factors for successful treatment-free remission in patients with chronic-phase chronic myeloid leukemia who discontinued tyrosine kinase inhibitors (TKIs). We also aimed to validate ddPCR for predicting molecular relapse.
This is a prospective, multicenter study.
We enrolled patients treated with TKIs for at least 3 years with a confirmed sustained deep molecular response (DMR) for at least 1 year. TKI was re-administered in patients who experienced the loss of major molecular response (MMR).
A total of 66 patients from five institutions in South Korea were enrolled. During a median follow-up period of 16.5 months, 29/66 (43.9%) patients experienced molecular relapse; the probability of molecular relapse-free survival (RFS) at 6 or 12 months after TKI discontinuation was 65.6% or 57.8%, respectively, with most molecular relapses occurring within the first 7 months. All patients who lost MMR were re-treated with TKI, and all re-achieved MMR at a median of 2.8 months. E14a2 transcript type ( = 0.005) and longer DMR duration (⩾48 months) prior to TKI discontinuation ( = 0.002) were associated with prolonged molecular RFS and with sustained DMR. Patients with both e13a2 transcript type and detectable (⩾MR) by ddPCR at the time of TKI discontinuation showed shorter duration of molecular RFS ( = 0.015).
Our data suggest that transcript type and transcript levels on ddPCR should be taken into consideration when deciding whether to discontinue TKI therapy.
液滴数字聚合酶链反应（ddPCR）是一种精确的测量方法。
我们开展本研究以确定停用酪氨酸激酶抑制剂（TKI）的慢性期慢性髓性白血病患者实现无治疗缓解的预后因素。我们还旨在验证ddPCR对预测分子复发的作用。
这是一项前瞻性多中心研究。
我们纳入了接受TKI治疗至少3年且确认持续深度分子反应（DMR）至少1年的患者。对出现主要分子反应（MMR）丧失的患者重新给予TKI治疗。
韩国5家机构共纳入66例患者。在中位随访期16.5个月期间，29/66（43.9%）例患者出现分子复发；TKI停药后6个月或12个月时分子无复发生存（RFS）概率分别为65.6%或57.8%，大多数分子复发发生在最初7个月内。所有MMR丧失的患者均重新接受TKI治疗，所有患者在中位2.8个月时均再次达到MMR。E14a2转录本类型（P = 0.005）以及TKI停药前较长的DMR持续时间（≥48个月）（P = 0.002）与延长的分子RFS以及持续的DMR相关。TKI停药时具有e13a2转录本类型且ddPCR检测到可检测水平（≥MR）的患者分子RFS持续时间较短（P = 0.015）。
我们的数据表明，在决定是否停用TKI治疗时应考虑转录本类型以及ddPCR上的转录本水平。
