Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 10: 1413 - 1419

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.10.006

Clinical research

Treatment-free remission after imatinib discontinuation in patients with chronic myeloid leukemia

  • Tianxue XU ,
  • Ying QIAN ,
  • Zhanyun LIU ,
  • Gang CAI ,
  • Yingli WU ,
  • Junmin LI ,
  • Zhixiang SHEN ,
  • Li ZHOU
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  • 1.Shanghai Institute of Hematology, Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    2.Department of Hematology, Shanghai Beizhan Hospital, Shanghai 200070, China
    3.Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
ZHOU Li, E-mail: zl10677@rjh.com.cn.

Received date: 2022-06-14

  Accepted date: 2022-09-18

  Online published: 2022-12-02

Supported by

National Natural Science Foundation of China(81570112)

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Abstract

Objective ·To analyze the outcomes of treatment-free remission (TFR) after imatinib discontinuation in patients with chronic myeloid leukemia in chronic phase (CML-CP) who meet the criteria for TFR and are willing to monitor the disease regularly, the prognostic factors and the application of droplet digital polymerase chain reaction (ddPCR) technique in monitoring TFR. Methods ·The patients with CML-CP enrolled in this study were monitored regularly after imatinib discontinuation. Molecular response and relapse were analyzed by quantitative polymerase chain reaction (QPCR) for detection of BCR-ABL transcripts. The lymphocytes subsets pre- and post-imatinib discontinuation were evaluated by flow cytometry. ddPCR was used to detect BCR-ABL and the predictive role in TFR was analyzed. Results ·① Forty-two CML-CP patients who met the criteria for TFR were assessed. With median follow-up time 41(5?93) months, 32 (76.2%) patients maintained TFR.The estimated TFR rate by 12, 24 and 48 months were 85.1%, 75.1% and 70.1%, respectively. Median TFR duration was 41 (2?93) months. The most common adverse event post-discontinuation was musculoskeletal pain of grade Ⅰ?Ⅱ (31.0%). Eight patients achieved deep molecular response (DMR) after restart of imatinib. ②58.3% of patients with continuous positive ddPCR developed molecular relapse after imatinib discontinuation, while none relapsed in those with negative detection (P<0.01). ③ The percentage of CD8+CD28- cells pre-discontinuation was lower, while the percentage of CD4+CD25+ cells post-discontinuation was higher in relapsed patients than that in TFR patients (6.2% vs 12.6%, P=0.026; 3.2% vs 2.1%, P=0.021). Conclusion ·CML-CP patients who meet the criteria of TFR may successfully maintain TFR after TKI discontinuation. ddPCR may help to predict the outcome of TFR and detect the molecular relapse earlier. Immune regulation by different T cell subsets may play a role in TFR duration to prevent relapse of disease.

Key words： treatment-free remission (TFR); imatinib; prognostic factor; chronic myeloid leukemia (CML); droplet digital polymerase chain reaction (ddPCR); lymphocyte subset

Cite this article

Tianxue XU , Ying QIAN , Zhanyun LIU , Gang CAI , Yingli WU , Junmin LI , Zhixiang SHEN , Li ZHOU . Treatment-free remission after imatinib discontinuation in patients with chronic myeloid leukemia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(10) : 1413 -1419 . DOI: 10.3969/j.issn.1674-8115.2022.10.006

References

1 SAGLIO G, GALE R P. Prospects for achieving treatment-free remission in chronic myeloid leukaemia[J]. Br J Haematol, 2020, 190(3): 318-327.
2 ROSS D M, HUGHES T P. Treatment-free remission in patients with chronic myeloid leukaemia[J]. Nat Rev Clin Oncol, 2020, 17(8): 493-503.
3 CERVEIRA N, BIZARRO S, TEIXEIRA M R, et al. When to stop TKIs in patients with chronic myeloid leukemia and how to follow them subsequently[J]. Curr Treat Options Oncol, 2021, 22(6): 49.
4 URESHINO H. Treatment-free remission and immunity in chronic myeloid leukemia[J]. Int J Hematol, 2021, 113(5): 642-647.
5 IRANI Y D, HUGHES A, CLARSON J, et al. Successful treatment-free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells[J]. Br J Haematol, 2020, 191(3): 433-441.
6 COLAFIGLI G, SCALZULLI E, DI PRIMA A, et al. Digital droplet PCR as a predictive tool for successful discontinuation outcome in chronic myeloid leukemia: is it time to introduce it in the clinical practice? [J]. Crit Rev Oncol Hematol, 2021, 157: 103163.
7 HOCHHAUS A, BACCARANI M, SILVER R T, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia[J]. Leukemia, 2020, 34(4): 966-984.
8 ETIENNE G, GUILHOT J, REA D, et al. Long-term follow-up of the French stop imatinib (STIM1) study in patients with chronic myeloid leukemia[J]. J Clin Oncol, 2017, 35(3): 298-305.
9 张丹, 朱焕玲. 慢性髓细胞白血病慢性期患者接受酪氨酸激酶抑制剂治疗停药后的临床结局及其影响因素临床分析[J]. 国际输血及血液学杂志, 2019, 42(2): 127-133.
9 ZHANG D, ZHU H L. Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia[J]. Int J Blood Transfus Hematol, 2019, 42(2): 127-133.
10 朱晓健, 游泳, 段明辉, 等. 慢性髓性白血病患者酪氨酸激酶抑制剂自动停药的多中心回顾性研究[J]. 中华血液学杂志, 2018, 39(12): 994-997.
10 ZHU X J,YOU Y, DUAN M H, et al. Tyrosine kinase inhibitors discontinuation for chronic myeloid leukemia: a multicenter retrospective analysis in China[J]. Chin J Hematol, 2018, 39(12): 994-997.
11 KIMURA S, IMAGAWA J, MURAI K, et al. Treatment-free remission after first-line dasatinib discontinuation in patients with chronic myeloid leukaemia (first-line DADI trial): a single-arm, multicentre, phase 2 trial[J]. Lancet Haematol, 2020, 7(3): e218-e225.
12 LEGROS L, NICOLINI F E, ETIENNE G, et al. Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia[J]. Cancer, 2017, 123(22): 4403-4410.
13 LEE S E, CHOI S Y, SONG H Y, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study[J]. Haematologica, 2016, 101(6): 717-723.
14 DIRAL E, LE COUTRE P, GOTTARDI E M, et al. Increased tumour burden over a 36 month period in chronic myeloid leukemia patients following imatinib discontinuation: role of digital PCR[J]. Blood, 2019,134(Suppl 1): 29.
15 COLAFIGLI G, SCALZULLI E, PORRAZZO M, et al. Digital droplet PCR at the time of TKI discontinuation in chronic-phase chronic myeloid leukemia patients is predictive of treatment-free remission outcome[J]. Hematol Oncol, 2019, 37(5): 652-654.
16 YAO D L, XU L, TAN J X. Re-balance of memory T cell subsets in peripheral blood from patients with CML after TKI treatment[J].Oncotarget, 2017, 8(47): 81852-81859.
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