Hematology Department, Hospital Clínico Universitario-INCLIVA, Valencia, Spain.
Hemotherapy and Hemostasis Department, Hospital Clínic-IDIBAPS, Barcelona, Spain.
Blood Cancer J. 2018 Dec 2;8(10):91. doi: 10.1038/s41408-018-0125-0.
Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients. Median follow-up from treatment discontinuation was 21.5 months and 5 patients died from CML-unrelated causes. TKI therapy was reinitiated due to MMR loss (n = 52), increase ≥ 1 log in BCR-ABL transcript level without losing MMR (n = 12), patient preference (n = 2), and withdrawal syndrome (n = 1). Treatment-free remission rate at 4 years was 64% (95% confidence interval, CI: 55%-72%). Cumulative incidence of molecular recurrence at 3 years was 33% (95% CI: 26%-38%). TKI treatment for < 5 years and MR4.5 duration shorter than 4 years were both associated with higher incidence of molecular recurrence. No patient had disease progression. Response status at last control was: MR4.5 (n = 196), MR4 (n = 15), MMR (n = 14), complete cytogenetic response (n = 10), and other (n = 1). A significant increase in Hb and cholesterol levels was observed after imatinib withdrawal. Our results demonstrate that TKI treatment discontinuation is feasible in real-life clinical practice.
超过一半的慢性髓性白血病(CML)患者在停止酪氨酸激酶抑制剂(TKI)治疗后不会失去主要分子反应(MMR)。这种策略在临床试验中是安全的,但在实际应用中仍存在争议。我们描述了 236 例 CML 患者的全国性系列中断 TKI 治疗后的结果。从治疗停止到随访的中位时间为 21.5 个月,有 5 例患者死于与 CML 无关的原因。由于 MMR 丧失(n=52)、BCR-ABL 转录水平增加≥1 个对数但未失去 MMR(n=12)、患者偏好(n=2)和停药综合征(n=1)而重新开始 TKI 治疗。4 年无治疗缓解率为 64%(95%置信区间:55%-72%)。3 年内分子复发的累积发生率为 33%(95%置信区间:26%-38%)。TKI 治疗时间<5 年和 MR4.5 持续时间<4 年与分子复发发生率增加有关。没有患者出现疾病进展。最后一次控制时的反应状态为:MR4.5(n=196)、MR4(n=15)、MMR(n=14)、完全细胞遗传学缓解(n=10)和其他(n=1)。伊马替尼停药后观察到 Hb 和胆固醇水平显著升高。我们的结果表明,TKI 治疗停药在实际临床实践中是可行的。