Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment
Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment
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DOI：
10.1016/j.clml.2018.03.004
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发表时间：
2018-05-01
影响因子：
2.7
通讯作者：
Kimura, Shinya
中科院分区：
文献类型：
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作者：
Okada, Masaya;Imagawa, Jun;Kimura, Shinya
我们描述了一项前瞻性试验的结果，该试验是在维持深度分子学缓解> 1年的慢性髓细胞白血病患者中停止二线达沙替尼治疗。36个月时无治疗缓解率为44.4%。高自然杀伤细胞计数前中止与成功therapeutic discontinuation.Introduction显着相关：我们以前报告了一个中期分析的DADI（达沙替尼停药）试验。结果显示，48%的慢性期慢性粒细胞白血病患者维持深度分子学缓解（DMR）>= 1年，可以在中位随访20个月时安全地停止二线或二线达沙替尼治疗。然而，从临床角度来看，更长随访期的结果将更有用。患者和方法：DADI试验是一项在日本进行的前瞻性多中心试验。在确认DMR稳定>= 1年后，停用伊马替尼或尼洛替尼后的达沙替尼治疗。停药后，DMR丢失（即使1分）定义为严格分子复发，从而触发治疗恢复。分析无治疗缓解（TFR）的预测因素.结果：中位随访期为44.0个月（四分位距，40.5-48.0个月）。36个月时估计的总体TFR率为44.4%（95%置信区间，32.0%-56.2%）。只有2例患者在1年截止点后发生分子复发。伊马替尼耐药的存在是分子复发的重要危险因素。此外，停药前高自然杀伤细胞和低γ δ（+）T细胞和CD 4（+）调节性T细胞（CD 25（+）CD 127（低））计数与成功停药显著相关。结论：这些结果表明，在持续DMR ≥ 1年后停用二线或二线达沙替尼是可行的，特别是对于无伊马替尼耐药史的患者。此外，自然杀伤细胞计数与TFR相关。
We describe the results of a prospective trial of the discontinuation of second-line dasatinib treatment in chronic myeloid leukemia patients who maintained a deep molecular response for > 1 year. The treatment- free remission rate at 36 months was 44.4%. High natural killer cell counts before discontinuation correlated significantly with successful therapy discontinuation.Introduction: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for >= 1 year could discontinue second-or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. Patients and Methods: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for >= 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment- free remission (TFR) were analyzed. Results: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low gamma delta(+) T-cell and CD4(+) regulatory T-cell (CD25(+)CD127(low)) counts before discontinuation correlated significantly with successful therapy discontinuation. Conclusion: These findings suggest that discontinuation of second-or subsequent-line dasatinib after a sustained DMR of >= 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.