Low-dose tyrosine kinase inhibitors in patients with chronic myeloid leukemia: a retrospective study in China

Chen, Yilin; Liu, Zelin; Zou, Jing; Wang, Danyu; He, Wenjuan; Li, Meng; Cheng, Fanjun; Li, Weiming

doi:10.3324/haematol.2022.280637

Cited by 6 publications

(13 citation statements)

References 14 publications

(18 reference statements)

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“…Moreover, dose-halving therapy yields higher molecular recurrence-free survival rate compared to direct TKI discontinuation ( Luo et al, 2022 ). Our recent study also confirmed the feasibility of TKI dose reduction therapy for Chinese CML patients ( Chen et al, 2022 ). The concern of whether dose reduction before TKI discontinuation affects patient’s access to TFR is also of interest to investigators.…”

Section: Introductionsupporting

confidence: 76%

Successful treatment discontinuation in CML patients with full-dose and low-dose TKI: Results from real-world practice

et al. 2023

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Background: In clinical studies, some patients who achieve deep molecular response (DMR) can successfully discontinue tyrosine kinase inhibitor (TKI). TKI dose reduction is also an important aspect of alleviating adverse effects and improving quality of life. This study aimed to explore the outcome after drug withdrawal in Chinese CML patients.Methods: We conducted a retrospective analysis of the outcome of 190 patients who stopped TKI. 27 patients experienced dose reduction before TKI discontinuation. The median duration of TKI treatment and MR4 before discontinuation was 82 months and 61 months.Results: With median follow-up after stopping TKI treatment of 17 months, the estimated TFR (Treatment Free Remission) were 76.9% (95%CI, 70.2%–82.4%), 68.8% (95%CI, 61.3%–75.2%), and 65.5% (95%CI, 57.4%–72.5%) at 6, 12 and 24 months. For full-dose and low-dose TKI groups, the TFR at 24 months was 66.7% and 55.8% (p = 0.320, log-rank). Most patients (56/57) quickly achieved MMR after restarting TKI treatment. Multivariable analysis showed that patients with TKI resistance had a higher risk of molecular relapse than patients without TKI resistance (p < 0.001).Conclusion: TFR rates were not impaired in patients experiencing dose reduction before TKI discontinuation compared to patients with full-dose TKI. Our data on Chinese population may provide a basis for the safety and feasibility of TKI discontinuation, including discontinuation after dose reduction, in clinical practice.

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Section: Introductionsupporting

confidence: 76%

Successful treatment discontinuation in CML patients with full-dose and low-dose TKI: Results from real-world practice

et al. 2023

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“…These limited prospective results demonstrated that low‐dose TKI is feasible and effective in newly diagnosed patients or patients with MMR. In our previous study, seven out of ten patients not in MMR achieved MMR or deeper molecular response with low‐dose treatment 36 . In a study of patients with prior TKI intolerance treated with low‐dose ponatinib, 40.4% patients had improved treatment response over a median of 19.2 months of ponatinib treatment 37 .…”

Section: Discussionmentioning

confidence: 92%

“…In our previous study, seven out of ten patients not in MMR achieved MMR or deeper molecular response with low‐dose treatment. 36 In a study of patients with prior TKI intolerance treated with low‐dose ponatinib, 40.4% patients had improved treatment response over a median of 19.2 months of ponatinib treatment. 37 These limited results suggested that low‐dose TKI could improve treatment response, but prospective studies with large samples are still needed to confirm.…”

Section: Discussionmentioning

confidence: 99%

Quality‐of‐life, mental health, and perspective on TKI dose reduction as a prelude to discontinuation in chronic phase chronic myeloid leukemia

Chen

Yang

et al. 2023

Cancer Medicine

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BackgroundTreatment‐free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality‐of‐life (QoL) and mental health in CML patients with full‐dose TKI, low‐dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation.MethodsWe conducted a cross‐sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation.Results1450 responses were included in the analysis. 44.3% of respondents reported a moderate‐to‐severe impact of TKI treatment on their QoL. 17% of respondents had moderate‐to‐severe anxiety. 24.4% of respondents had moderate‐to‐severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long‐term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full‐dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping.ConclusionsTKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation.Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality‐of‐life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.

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“…Первоначально дозы ИТК разрабатывались в рамках стратегии, аналогично используемой для химиотерапии, т. е. дозы, на один уровень ниже максимально переносимой. Позднее было установлено, что эффективность препарата может быть аналогичной или сохраняться после достижения ответа при более низких дозах ИТК [70,77,[82][83][84]. Продолжительный опыт применения ИТК при ХМЛ обозначил новую концепцию в терапии опухоли -разработку долгосрочной таргетной терапии в оптимальной биологической дозе [85][86][87][88].…”

Section: сниженные дозы ингибиторов тирозинкиназ: кому и когдаunclassified

25 years of experience in the treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: results, opportunities, questions

Tsyba,

Turkina

2024

Medicinskij sovet

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More than 25 years ago, the discovery of imatinib, the first ATP-competitive inhibitor of BCR::ABL1, the driving oncoprotein of chronic myeloid leukemia, revolutionized patients life by transforming a fatal condition into a chronic disease. The review analyzes data on the effectiveness of chronic myeloid leukemia therapy with tyrosine kinase inhibitors and a number of provisions that require discussion and, possibly, revision at the present stage. The first clinical trials of imatinib, the first ATP- competitive inhibitor of BCR::ABL1, started in 1998, demonstrated extremely high therapeutic efficacy, impressively increasing the rates of relapse-free and overall survival in patients with chronic myeloid leukemia. The life expectancy of the overwhelming number of patients has become comparable to the life expectancy of the main population. Over the years, the arsenal of therapeutic agents for the treatment of chronic myeloid leukemia has been significantly enriched: three ATP-competitive tyrosine kinase inhibitors of the 2nd generation have been created and approved for use, 2 drugs of the 3rd generation: ponatinib, and the first allosteric tyrosine kinase inhibitor asciminib have been registered for the treatment of patients with the T315I mutation. Regular cytogenetic and molecular genetic monitoring makes it possible to adequately assess the volume of the leukemic clone and is an integral part of evaluating the effectiveness of therapy, allowing to control and maintain remission in a number of patients without the use of tyrosine kinase inhibitors. Today imatinib remains the key drug of the 1st line of therapy, at the same time, the appointment of 2nd generation tyrosine kinase inhibitors in the first line of therapy can lead to an earlier and deeper response. The choice of the drug for each individual patient, taking into account the best tolerability and maximum effectiveness, allows individualizing treatment and expanding the possibilities of therapy.

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Low-dose tyrosine kinase inhibitors in patients with chronic myeloid leukemia: a retrospective study in China

Abstract: Not available.

Cited by 6 publications

References 14 publications

Successful treatment discontinuation in CML patients with full-dose and low-dose TKI: Results from real-world practice

Successful treatment discontinuation in CML patients with full-dose and low-dose TKI: Results from real-world practice

Quality‐of‐life, mental health, and perspective on TKI dose reduction as a prelude to discontinuation in chronic phase chronic myeloid leukemia

25 years of experience in the treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: results, opportunities, questions

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