Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo, Sao Paulo, SP, Brazil.
Instituto do Câncer do Estado de São Paulo, Sao Paulo, SP, Brazil.
Leuk Res. 2021 Feb;101:106516. doi: 10.1016/j.leukres.2021.106516. Epub 2021 Jan 21.
Treatment-free survival (TFS) in chronic myeloid leukemia (CML) is a new goal. This prospective study aims to evaluate imatinib discontinuation's feasibility and safety in patients with deep molecular response MR4 (BCR-ABL1 < 0.01 % IS).
Study was approved by the ethical committee and registered at Clinicaltrials.gov (NCT03239886). Incluision criteria were: age ≥ 18y, chronic phase, first-line imatinib for 36 months, MR4 for 12 months, no previous transplant or resistance. Imatinib was resumed when two samples confirmed the loss of MMR. The primary endpoint was molecular recurrence-free survival (MRFS) at 24 months. Lymphocyte subpopulations were counted in peripheral blood before discontinuation.
31 patients were included from Dec/2016 until Oct/2017. Median age was 54years, 58 % male, 58 % low Sokal, 65 % b3a2 transcripts, and 61 % were in MR4.5. Imatinib therapy's median time was 9.7y (3-14.9 y), median time of MR4 was 6.9y (1.6-10.3y). MRFS at 24 months was 55 % (95 % CI 39-75). Thirteen patients relapsed, 46 % after six months of discontinuation, and all patients recovered MMR. Median time to recover MMR was one month. MR4.5 was the only factor associated with MRFS. NK cells proportion at baseline was lower in patients with only MR4 who relapsed after discontinuation.
With a median duration of sustained MR4 above five years, as recommended by most TKI discontinuation guidelines, the TFS was similar to previous studies. Only MR4.5 was associated with lower risk of relapse. Further studies are needed to evaluate whether patients with only MR4 and low NK cell levels are suitable for discontinuation.
慢性髓性白血病（CML）的无治疗生存（TFS）是一个新的目标。这项前瞻性研究旨在评估在达到深度分子学反应 MR4（BCR-ABL1 < 0.01%IS）的患者中停止伊马替尼治疗的可行性和安全性。
该研究获得了伦理委员会的批准，并在 ClinicalTrials.gov 上注册（NCT03239886）。纳入标准为：年龄≥18 岁，慢性期，一线伊马替尼治疗 36 个月，MR4 持续 12 个月，无既往移植或耐药。当两次样本确认失去主要分子反应（MMR）时，重新开始伊马替尼治疗。主要终点是 24 个月时的分子无复发生存率（MRFS）。在停药前，检测外周血中的淋巴细胞亚群。
2016 年 12 月至 2017 年 10 月期间共纳入 31 例患者。中位年龄为 54 岁，58%为男性，58%为低危 Sokal 评分，65%为 b3a2 转录本，61%处于 MR4.5。伊马替尼治疗的中位时间为 9.7 年（3-14.9 年），MR4 的中位时间为 6.9 年（1.6-10.3 年）。24 个月时的 MRFS 为 55%（95%CI39-75）。13 例患者复发，46%在停药后 6 个月内复发，所有患者均恢复 MMR。恢复 MMR 的中位时间为 1 个月。仅 MR4.5 是与 MRFS 相关的唯一因素。在停药后仅 MR4 复发的患者中，基线时 NK 细胞比例较低。
根据大多数 TKI 停药指南的建议，在持续达到深度分子学反应 MR4 超过五年的中位时间后，TFS 与之前的研究相似。仅 MR4.5 与较低的复发风险相关。需要进一步研究评估仅达到 MR4 和低 NK 细胞水平的患者是否适合停药。
