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尝试停用酪氨酸激酶抑制剂的慢性髓性白血病患者的临床特征与 T 细胞受体库：ISAC-TFR 研究

英文原题：Clinical Features and T-Cell Repertoire of Chronic Myeloid Leukemia Patients Who Attempt Discontinuation of Tyrosine Kinase Inhibitors: The ISAC-TFR Study.

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Clinical Features and T-Cell Repertoire of Chronic Myeloid Leukemia Patients Who Attempt Discontinuation of Tyrosine Kinase Inhibitors: The ISAC-TFR Study.

PubMed 2025/08/01（内容时间） Cancer Med Q2 · IF 3.5（JCR 2025）

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技术：NK 细胞慢性髓系白血病地区：日本
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研究概要

达到深度分子学反应（DMR）的 CML 患者的 T 细胞免疫可能已十分接近健康个体。

中文摘要

背景

酪氨酸激酶抑制剂（TKI）停药已是明确的治疗目标，但首次尝试停药后最多有 60% 的患者复发。再次或第三次尝试停用 TKI 是否可行仍不确定。免疫监视，尤其是 T 细胞和自然杀伤（NK）细胞应答，可能影响无治疗缓解（TFR），但尚无可预测 TFR 持续维持的确切生物标志物。

方法

本回顾性研究纳入 57 例尝试停用 TKI 的慢性髓性白血病（CML）患者，分析首次、第二次和第三次 TFR 尝试后的临床结局，并对 14 例患者的外周血样本进行 T 细胞受体（TCR）和 B 细胞受体（BCR）库分析，以研究与 TFR 相关的免疫图景。

结果

1 年 TFR1 率为 67.9%（95% 置信区间［CI］53.9%–78.4%）。16 例患者尝试第二次停药，1 年 TFR2 率为 31.2%（95% CI 11.4%–53.6%）。停用 TKI 后 3 个月 BCR::ABL1 mRNA 水平维持在 MR 4.5 以下的患者，复发风险显著较低（HR 0.099；95% CI 0.012–0.829；p = 0.033）。TCR 库分析未发现明确的 T 细胞克隆扩增，但观察到 T 细胞多样性随年龄增长显著下降。

结论

达到深度分子学缓解（DMR）的 CML 患者，其 T 细胞免疫可能与健康人群相近。

展开英文摘要原文
BACKGROUND

While tyrosine kinase inhibitor (TKI) discontinuation is an established therapeutic goal, up to 60% of patients relapse after the first attempt. The feasibility of a second or third attempt at TKI discontinuation remains uncertain. Immune surveillance, particularly T-cell and natural killer (NK) cell responses, may influence treatment-free remission (TFR), although no definitive biomarkers for predicting sustained TFR have been identified.

METHODS

This retrospective study included 57 chronic myeloid leukemia (CML) patients who attempted TKI discontinuation. Clinical outcomes after the first, second, and third TFR attempts were analyzed, and T cell receptor (TCR) and B-cell receptor (BCR) repertoire analyses were conducted on peripheral blood samples from 14 patients to investigate the immune landscape associated with TFR.

RESULTS

TFR1 at 1 year was 67.9% (95% confidence interval [CI], 53.9%-78.4%). Sixteen patients attempted a second discontinuation, achieving a 1-year TFR2 rate of 31.2% (95% CI, 11.4%-53.6%). Patients maintaining BCR::ABL1 mRNA levels below MR 4.5 at 3 months post-TKI discontinuation had a significantly lower risk of relapse (HR, 0.099; 95% CI, 0.012-0.829; p = 0.033). TCR repertoire analysis did not reveal distinct clonal expansions of T cells; however, a significant age-related decline in T-cell diversity was observed.

CONCLUSION

T-cell immunity in CML patients who have achieved a deep molecular response (DMR) may closely approximate that observed in healthy individuals.

论文信息

作者
Ureshino H、Nakamura Y、Budirahardja Y、Nozawa I、Kidoguchi K、Kamachi K、Kimura S
单位
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine Saga University, Saga, Japan.Japan
期刊
Cancer medicine2025 Aug
原文标识
PubMed 40785616　·　DOI 10.1002/cam4.71142

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