慢性髓系白血病慢性期TKI治疗未达最佳反应或不耐受患者转换氟马替尼的有效性和安全性临床观察

杨松凡; 文钦; 张颖; 吕敬龙; 舒华娥; 颜红菊; 张诚; 魏锦; 张曦

doi:10.16016/j.2097-0927.202310076

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慢性髓系白血病慢性期TKI治疗未达最佳反应或不耐受患者转换氟马替尼的有效性和安全性临床观察

专题报道：血液肿瘤诊治前沿 | 更新时间：2026-01-09

- 慢性髓系白血病慢性期TKI治疗未达最佳反应或不耐受患者转换氟马替尼的有效性和安全性临床观察
- Efficacy and safety of switching to flumatinib in patients with chronic myeloid leukemia who have not achieved optimal response or are intolerant to TKI treatment
- 陆军军医大学学报 2024年46卷第4期页码：340-346
- 作者机构：
  
  1.637002 南充，川北医学院附属医院血液科
  2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院血液病医学中心，全军临床重点专科，创伤与化学中毒全国重点实验室，重庆市临床重点专科，血液病与微环境重庆市重点实验室
  3.401336 重庆，重庆医科大学第二附属医院血液科
  4.404100 重庆，重庆大学附属三峡医院血液科
  5.405400 重庆，开州区人民医院血液科
  6.401329 重庆，金凤实验室
- 作者简介：
  
  [张曦，E-mail: zhangxxi@sina.comZHANG Xi, E-mail: zhangxxi@sina.com
- 基金信息：
  
  重庆市科卫联合医学科研面上项目(2023MSXM079);重庆市技术创新与应用发展专项面上项目(cstc2019jscx-msxmX0147)
- DOI：10.16016/j.2097-0927.202310076
  中图分类号： R181.32;R733.7;R979.12
- 收稿：2023-10-20，
  
  修回：2023-12-25，
  
  纸质出版：2024-02-28
- 稿件说明：
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杨松凡, 文钦, 张颖, 等. 慢性髓系白血病慢性期TKI治疗未达最佳反应或不耐受患者转换氟马替尼的有效性和安全性临床观察[J]. 陆军军医大学学报, 2024,46(4):340-346.

Songfan YANG, Qin WEN, Ying ZHANG, et al. Efficacy and safety of switching to flumatinib in patients with chronic myeloid leukemia who have not achieved optimal response or are intolerant to TKI treatment[J]. Journal of Army Medical University, 2024, 46(4): 340-346.
杨松凡, 文钦, 张颖, 等. 慢性髓系白血病慢性期TKI治疗未达最佳反应或不耐受患者转换氟马替尼的有效性和安全性临床观察[J]. 陆军军医大学学报, 2024,46(4):340-346. DOI： 10.16016/j.2097-0927.202310076.

Songfan YANG, Qin WEN, Ying ZHANG, et al. Efficacy and safety of switching to flumatinib in patients with chronic myeloid leukemia who have not achieved optimal response or are intolerant to TKI treatment[J]. Journal of Army Medical University, 2024, 46(4): 340-346. DOI： 10.16016/j.2097-0927.202310076.

摘要

目的

观察TKI未达最佳反应或不耐受的慢性髓系白血病-慢性期(chronic myelogenous leukemia-chronicphase

CML-CP)患者转换氟马替尼治疗的效果及安全性。

方法

从重庆市医院及川北医学院附属医院共5家医院收集2020年2月至2022年8月对一线伊马替尼、达沙替尼、尼洛替尼未达最佳反应或不耐受

转换氟马替尼(600 mg/d)治疗的患者

观察氟马替尼的疗效及安全。统计患者治疗3、6、12个月时最佳反应率及主要分子学反应(major molecular response

MMR)率、累积完全细胞遗传学反应(complete cytogenetic response

CCyR)率、累积MMR率、累积深度分子学反应(deep molecular response

DMR)率、无进展生存(progression-free survival

PFS)、无事件生存(event-free survival

EFS)情况及不良反应情况。

结果

共纳入100例CML-CP患者

中位随访时间为18(3~36)个月

3、6、12个月最佳反应率分别为92.6%(88/95)、94.4%(85/90)和92.9%(79/85)

随访截止至2023年8月20日

累积CCyR、MMR率分别为98.0%(98/100)、81.9%(77/94)

达CCyR和MMR的中位时间均为3个月

累积DMR率为51.0%(51/100)。随访时间内

PFS率为100.0%(100/100)

1年EFS率为85.6%(75/90)。氟马替尼最常见非血液学不良反应为腹泻腹痛(7.0%)

其次为肾功能损害(6.0%)、肌肉骨骼疼痛(2.0%); 血液学不良反应主要有血小板减少(12.0%)、贫血(6.0%)和白细胞减少(2.0%)。

结论

氟马替尼治疗TKI未达最佳反应或不耐受的CML-CP患者有较好的MMR和DMR

耐受性及安全性良好。

Abstract

Objective

To observe the efficacy and safety of flumatinib conversion in chronic myelogenous leukemia-chronicphase (CML-CP) patients with suboptimal TKI response or intolerance.

Methods

Patients who did not have the best response or intolerance to first-line imatinib

dasatinib

and nilotinib and switched to flumatinib (600 mg/d) from February 2020 to August 2022 were collected from 5 hospitals from Chongqing and affiliated hospitals of North Sichuan Medical College.The efficacy and safety of flumatinib were observed.The optimal response rate

major molecular response (MMR)

cumulative complete cytogenetic response (CCyR) rate

cumulative MMR rate

cumulative deep molecular response (DMR)

progression-free survival (PFS)

event-free survival (EFS) and adverse reactions in 3

6 and 12 months after treatment were observed and analyzed.

Results

A total of 100 patients with CML-CP were enrolled

with a median follow-up of 18(3~36) months.The optimal response rate was 92.6%(88/95)

94.4%(85/90) and 92.9%(79/85) respectively

at 3

6 and 12 months after treatment.Till August 20

2023

the cumulative CCyR and MMR rate was 98.0%(98/100) and 81.9%(77/94)

respectively

the median time to reach CCyR and MMR was 3 months

and cumulative DMR rate was 51.0%(51/100).PFS rate was 100.0%(100/100) and 1-year EFS rate was 85.6%(75/90).The most common non-hematologic adverse reactions of flumatinib were diarrhea and abdominal pain (7.0%)

followed by renal dysfunction (6.0%) and musculoskeletal pain (2.0%).The main hematologic adverse reactions were thrombocytopenia (12.0%)

anemia (6.0%) and leukopenia (2.0%).

Conclusion

Flumatinib has better MMR and DMR and is well tolerated in CML-CP patients with TKI resistance or intolerance.

关键词

Keywords

references

ROWLEY J D. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining[J]. Nature, 1973, 243(5405): 290-293. DOI: 10.1038/243290a0.

HEHLMANN R, LAUSEKER M, SAUßELE S, et al . Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study Ⅳ and impact of non-CML determinants[J ] . Leukemia, 2017, 31(11): 2398-2406. DO I: 10.1038/leu.2017.253.

BOWER H, BJÖRKHOLM M, DICKMAN P W, et al . Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population[J ] . J Clin Oncol, 2016, 34(24): 2851-2857. DOI: 10.1200/JCO.2015.66.2866.

DRUKER B J, GUILHOT F, O'BRIEN S G, et al . Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia[J ] . N Engl J Med, 2006, 355(23): 2408-2417. DOI: 10.1056/NEJMoa062867.

SHAH N P, ROUSSELOT P, SCHIFFER C, et al . Dasatinib in imatinib-resistant or-intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034[J ] . Am J Hematol, 2016, 91(9): 869-874. DOI: 10.1002/ajh.24423.

KANTARJIAN H M, GILES F, GATTERMANN N, et al . Nilotinib (formerly AMN 107 ), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance[J ] . Blood, 2007, 110(10): 3540-3546. DOI: 10.1182/blood-2007-03-080689..

CORTES J E, JIMENE Z C A, MAURO M J, et al . Pleural effusion in dasatinib-treated patients with chronic myeloid leukemia in chronic phase: identification and management[J ] . Clin Lymphoma Myeloma Leuk, 2017, 17(2): 78-82. DOI: 10.1016/j.clml.2016.09.012.

KANTARJIAN H M, HUGHES T P, LARSON R A, et al . Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis[J ] . Leukemia, 2021, 35(2): 440-453. DOI: 10.1038/s41375-020-01111-2.

ZHANG L, MENG L, LIU B C, et al . Flumatinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: a phase Ⅲ, randomized, open-label, multi-center FESTnd study[J ] . Clin Cancer Res, 2021, 27(1): 70-77. DOI: 10.1158/1078-0432.CCR-20-1600.

中华医学会血液学分会. 慢性髓性白血病中国诊断与治疗指南(2020年版)[J]. 中华血液学杂志, 2020, 41(5): 353-364. DOI: 10.3760/cma.j.issn.0253-2727.2020.05.001.

Chinese Society of Hematology of Chinese Medical Association. The guidelines for diagnosis and treatment of chronic myeloid leukemia in China(2020 edition)[J]. Chin J Hematol, 2020, 41(5): 353-364. DOI: 10.3760/cma.j.issn.0253-2727.2020.05.001.

CHIN R, LEE B Y. Common terminology criteria for adverse events v3.0 (CTCAE)[M ] // Princ iples and practice of clinical trial medicine. New York: Academic Press, 2008: 461-533. DOI: 10.1016/B978-0-12-373695-6.00022-3 http://dx.doi.org/10.1016/B978-0-12-373695-6.00022-3 .

BACCARANI M, CORTES J, PANE F, et al . Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet[J ] . J Clin Oncol, 2009, 27(35): 6041-6051. DOI: 10.1200/JCO.2009.25.0779.

DUSETZINA S B, WINN A N, ABEL G A, et al . Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia[J ] . J Clin Oncol, 2014, 32(4): 306-311. DOI: 10.1200/JCO.2013.52.9123.

IBRAHIM A R, ELIASSON L, APPERLEY J F, et al . Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy[J ] . Blood, 2011, 117(14): 3733-3736. DOI: 10.1182/blood-2010-10-309807.

FERDINAND R, MITCHELL S A, BATSON S, et al . Treatments for chronic myeloid leukemia: a qualitative systematic review[J ] . J Blood Med, 2012, 3: 51-76. DOI: 10.2147/JBM.S33380.

郭勇鑫, 陆天, 陈文明, 等. 氟马替尼治疗伊马替尼耐药或不耐受慢性粒细胞白血病的效果及安全性[J]. 白血病·淋巴瘤, 2023, 32(1): 45-50. DOI: 10.3760/cma.j.cn115356-20220712-00203.

GUO Y X, LU T, CHEN W M, et al . Efficacy and safety of flumatinib in treatment of imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia[J ] . J Leuk Lymphoma, 2023, 32(1): 45-50. DOI: 10.3760/cma.j.cn115356-20220712-00203.

HEHLMANN R, CORTES J E, ZYCZYNSKI T, et al . Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic-phase chronic myeloid leukemia in routine clinical practice: simplicity[J ] . Am J Hematol, 2019, 94(1): 46-54. DOI: 10.1002/ajh.25306.

GUÉRIN A, CHEN L, IONESCU-ITTU R, et al . Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase[J ] . Curr Med Res Opin, 2014, 30(11): 2317-2328. DOI: 10.1185/03007995.2014.944973.

RASHEED W, FLAIM B, SEYMOUR J F. Reversible severe pulmonary hypertension secondary to dasatinib in a patient with chronic myeloid leukemia[J]. Leuk Res, 2009, 33(6): 861-864. DOI: 10.1016/j.leukres.2008.09.026.

MINAMI M, ARITA T, IWASAKI H, et al . Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib[J ] . Br J Haematol, 2017, 177(4): 578-587. DOI: 10.1111/bjh.14608.

YANG M J, XI Q M, JIA W Q, et al . Structure-based analysis and biological characterization of imatinib derivatives reveal insights towards the inhibition of wild-type BCR-ABL and its mutants[J ] . Bioorg Med Chem Lett, 2019, 29(24): 126758. DOI: 10.1016/j.bmcl.2019.126758.

LUO H, QUAN H, XIE C, et al . HH-GV-678, a novel selective inhibitor of Bcr-Abl, outperforms imatinib and effectively overrides imatinib resistance[J ] . Leukemia, 2010, 24(10): 1807-1809. DOI: 10.1038/leu.2010.169.

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