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WT1 mRNA 外周血动态变化对接受 venetoclax 联合治疗的急性髓系白血病患者预后的影响。

Prognostic impact of peripheral blood WT1 mRNA dynamics in patients with acute myeloid leukemia treated with venetoclax combination therapy.

机构信息

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Department of Hematology, Hiraka General Hospital, Yokote, Japan.

出版信息

Int J Clin Oncol. 2024 Apr;29(4):481-492. doi: 10.1007/s10147-024-02480-9. Epub 2024 Feb 9.

DOI:10.1007/s10147-024-02480-9
PMID:38334897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10963556/
Abstract

BACKGROUND

Wilms' tumor gene 1 (WT1) mRNA quantification is a useful marker of measurable residual disease in acute myeloid leukemia (AML). However, whether monitoring the WT1 mRNA levels may predict the outcome of venetoclax (VEN) combination therapy in AML is not reported. This study aims to elucidate whether WT1 mRNA dynamics could predict long-term prognosis.

METHODS

33 patients with untreated or relapsed/refractory AML evaluated for peripheral blood WT1 dynamics in VEN combination therapy were analyzed.

RESULTS

The median age was 73 years (range 39-87). Azacitidine was combined with VEN in 91% of patients. Overall, the median overall survival (OS) was 334 days (95% CI 210-482), and the complete remission (CR) plus CR with incomplete hematologic recovery rate was 59%. A 1-log reduction of WT1 mRNA values by the end of cycle 2 of treatment was associated with significantly better OS and event-free survival (EFS) (median OS 482 days vs. 237 days, p = 0.049; median EFS 270 days vs. 125 days, p = 0.02). The negativity of post-treatment WT1 mRNA value during the treatment was associated with significantly better OS and EFS (median OS 482 days vs. 256 days, p = 0.02; median EFS not reached vs. 150 days, p = 0.005). Multivariate analysis confirmed the significance of these two parameters as strong EFS predictors (HR 0.26, p = 0.024 and HR 0.15, p = 0.013, respectively). The increase in WT1 mRNA values was correlated with relapse.

CONCLUSION

This study demonstrates that WT1 mRNA dynamics can be a useful marker for assessing long-term prognosis of VEN combination therapy for AML.

摘要

背景

Wilms 肿瘤基因 1（WT1）mRNA 定量是急性髓细胞白血病（AML）可测量残留疾病的有用标志物。然而，监测 WT1 mRNA 水平是否可以预测 AML 中 venetoclax（VEN）联合治疗的结果尚未报道。本研究旨在阐明 WT1 mRNA 动力学是否可以预测长期预后。

方法

对 33 例接受未经治疗或复发/难治性 AML 患者的外周血 WT1 动力学进行 VEN 联合治疗评估。

结果

中位年龄为 73 岁（范围 39-87 岁）。91%的患者联合使用阿扎胞苷和 VEN。总体而言，中位总生存期（OS）为 334 天（95%CI 210-482），完全缓解（CR）加不完全血液学恢复率为 59%。治疗第 2 周期结束时 WT1 mRNA 值降低 1 个对数可显著改善 OS 和无事件生存（EFS）（中位 OS 482 天比 237 天，p=0.049；中位 EFS 270 天比 125 天，p=0.02）。治疗过程中治疗后 WT1 mRNA 值的阴性与显著更好的 OS 和 EFS 相关（中位 OS 482 天比 256 天，p=0.02；中位 EFS 未达到比 150 天，p=0.005）。多变量分析证实了这两个参数作为 EFS 强预测因子的意义（HR 0.26，p=0.024 和 HR 0.15，p=0.013）。WT1 mRNA 值的增加与复发相关。

结论

本研究表明，WT1 mRNA 动力学可作为评估 AML VEN 联合治疗长期预后的有用标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/2d7549d23d54/10147_2024_2480_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/481e862aa20a/10147_2024_2480_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/2d1cb1a25e0d/10147_2024_2480_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/2d7549d23d54/10147_2024_2480_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/481e862aa20a/10147_2024_2480_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/337aa2c6b1c5/10147_2024_2480_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/82adc17db046/10147_2024_2480_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/6c09d5c7f762/10147_2024_2480_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/2d1cb1a25e0d/10147_2024_2480_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b9/10963556/2d7549d23d54/10147_2024_2480_Fig6_HTML.jpg

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本文引用的文献

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Measurable Residual Disease Response and Prognosis in Treatment-Naïve Acute Myeloid Leukemia With Venetoclax and Azacitidine.维奈托克联合阿扎胞苷治疗初治急性髓系白血病的微小残留病反应与预后。
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Early detection of WT1 measurable residual disease identifies high-risk patients, independent of transplantation in AML.在 AML 中，WT1 可测量残留病的早期检测可识别高危患者，与移植无关。
Blood Adv. 2021 Dec 14;5(23):5258-5268. doi: 10.1182/bloodadvances.2021004322.
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Prognostic impact of pretransplant measurable residual disease assessed by peripheral blood WT1-mRNA expression in patients with AML and MDS.移植前外周血 WT1-mRNA 表达评估的可测量残留病对 AML 和 MDS 患者的预后影响。
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