Service d'Oncologie Hématologique et Thérapie Cellulaire, CHU Poitiers, Poitiers, France.
INSERM CIC 1402, CHU Poitiers, Poitiers, France.
Cancer. 2020 Aug 1;126(15):3438-3447. doi: 10.1002/cncr.32940. Epub 2020 May 27.
Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). In clinical practice, tyrosine kinase inhibitor (TKI) dose reductions can be considered a means of preventing adverse effects and improving quality of life. We hypothesized that administration of low-dose TKIs before treatment discontinuation does not impair TFR in patients with CML who have a deep molecular response (DMR, ≥MR ).
We conducted a retrospective analysis of 77 patients with CML who discontinued treatment with TKIs. Twenty-six patients had been managed with low-dose TKIs before stopping treatment. Patients were to be exposed to TKIs for ≥5 years and to low-dose TKIs for ≥1 year and in DMR for ≥2 years. The loss of major molecular response (MMR) was considered a trigger for restarting therapy.
In the low-dose group, 61.5% of patients received second-generation TKIs, and dose reduction was ≥50% for 65.4% of patients. With a median follow-up of 61.5 months, TFR at 12 months was 56.8% in the full-dose TKI group and 80.8% in the low-dose group, and TFR at 60 months was 47.5% and 58.8%, respectively. The median time to molecular recurrence (≥MMR) from TKI discontinuation in the entire cohort was 6.2 months. All patients quickly achieved MMR after resuming TKI therapy. Results appear independent of both dose reduction and potential pretreatment with interferon-α.
This retrospective study shows that TFR was not impaired by low-dose TKI regimens before TKI cessation in Patients with CML. Nevertheless, prospective randomized clinical trials must be undertaken to analyze the probability of successful TFR in patients managed with TKI dose de-escalation strategies before TKI discontinuation.
长期无治疗缓解（TFR）是慢性髓性白血病（CML）的一个新目标。在临床实践中，可考虑减少酪氨酸激酶抑制剂（TKI）剂量以预防不良反应和提高生活质量。我们假设，在 CML 患者达到深度分子反应（DMR，≥MR ）后，在停止 TKI 治疗前给予低剂量 TKI 不会损害 TFR。
我们对 77 例停止 TKI 治疗的 CML 患者进行了回顾性分析。26 例患者在停止治疗前接受了低剂量 TKI 治疗。患者需要接受 TKI 治疗至少 5 年，低剂量 TKI 治疗至少 1 年，DMR 持续至少 2 年。主要分子学缓解（MMR）丧失被认为是重新开始治疗的触发因素。
在低剂量组中，61.5%的患者接受了第二代 TKI，65.4%的患者剂量减少了≥50%。中位随访 61.5 个月时，全剂量 TKI 组的 12 个月 TFR 为 56.8%，低剂量组为 80.8%，60 个月时 TFR 分别为 47.5%和 58.8%。整个队列中从 TKI 停药到分子复发（≥MMR）的中位时间为 6.2 个月。所有患者在重新开始 TKI 治疗后很快就达到了 MMR。结果似乎与剂量减少和潜在的干扰素-α预处理无关。
这项回顾性研究表明，在 CML 患者中，在停止 TKI 治疗前使用低剂量 TKI 方案不会损害 TFR。然而，必须进行前瞻性随机临床试验，以分析在停止 TKI 治疗前采用 TKI 剂量下调策略管理的患者成功实现 TFR 的可能性。
