Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea.
Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Leuk Res. 2021 Jun;105:106578. doi: 10.1016/j.leukres.2021.106578. Epub 2021 Mar 31.
Molecular response (MR) 4.0 or 4.3 remains an indicator of treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) in countries that accept it as the criterion of undetectable minimal residual disease (UMRD) in clinical practice. We retrospectively analyzed the TFR outcomes to identify the clinical efficacy of MR4.0/4.3 as the UMRD criterion.
CML patients treated with tyrosine kinase inhibitors (TKIs) between March 2001 and May 2015 for >3 years and treatment cessation for over 6 months were included. TFR was analyzed using MR3.0 loss and UMRD loss as criteria. TFR failure-free survival was defined as the time from cessation of TKI therapy to MR loss or restarting TKI, and overall survival as the time from TKI cessation to death. The probability of regaining the MR was evaluated.
In the 93 participants, the median duration of follow-up and TKI therapy were 17.3 (3.9-92.0) months and 7.4 (3.1-16.9) years, respectively. TFR at 5 years was 47.9 % and 44.4 %, for MR3.0 loss and UMRD loss, respectively. Among the 42 patients who restarted TKI, 41 regained MR3.0 (97.6 %). In multivariate analysis, the time to UMRD was ≤12 months, and the absence of prior TKI treatment (P = 0.018 and 0.044 in UMRD loss, respectively) was significantly correlated with TFR failure-free survival.
Clinical outcomes were comparable to those of clinical trials. Our results suggest that the detection limit of MR4.3 can be used in clinical practice for TKI treatment cessation for TFR in CML patients.
在接受分子学应答 4.0 或 4.3 作为不可检测微小残留病灶（UMRD）标准的国家，分子学应答 4.0 或 4.3 仍然是慢性髓性白血病（CML）患者无治疗缓解（TFR）的指标。我们回顾性分析了 TFR 结果，以确定作为 UMRD 标准的 MR4.0/4.3 的临床疗效。
纳入 2001 年 3 月至 2015 年 5 月期间接受酪氨酸激酶抑制剂（TKI）治疗超过 3 年且停药超过 6 个月的 CML 患者。采用 MR3.0 丢失和 UMRD 丢失作为标准分析 TFR。TFR 无失败生存定义为停止 TKI 治疗至 MR 丢失或重新开始 TKI 的时间，总生存定义为停止 TKI 治疗至死亡的时间。评估恢复 MR 的概率。
在 93 名参与者中，中位随访和 TKI 治疗时间分别为 17.3（3.9-92.0）个月和 7.4（3.1-16.9）年。MR3.0 丢失和 UMRD 丢失的 5 年 TFR 分别为 47.9%和 44.4%。在重新开始 TKI 的 42 名患者中，41 名患者恢复了 MR3.0（97.6%）。多变量分析显示，UMRD 时间≤12 个月和无 TKI 治疗史（UMRD 丢失时 P=0.018 和 0.044）与 TFR 无失败生存显著相关。
临床结果与临床试验相当。我们的结果表明，MR4.3 的检测限可用于临床实践中停止 TKI 治疗以实现 CML 患者的 TFR。
