Withdrawal Syndrome After Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI

Петрова, А. Л.; Chelysheva, Ekaterina; Shukhov, Oleg; Bykova, Anastasiya; Nemchenko, Irina; Gusarova, Galina A.; Tsyba, Nikolay; Julhakyan, Hunan; Shuvaev, Vasiliy; Фоминых, М. С.; Martynkevich, Irina; Ionova, Tatyana; Turkina, Anna

doi:10.1016/j.clml.2019.12.019

Cited by 11 publications

(10 citation statements)

References 25 publications

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“…Imatinib withdrawal syndrome was associated with a higher probability of sustained MMR than patients without withdrawal syndrome (79.5% vs. 49.2%, P=0.003) in the KID study (19). However, no association between withdrawal syndrome development and the rate of molecular relapses was found in the RU-SKI study (38). These results substantiate patients with deeper molecular responses and a longer duration of molecular responses before stopping TKI had higher rates of TFR.…”

Section: Clinical Indicatorsmentioning

confidence: 62%

“…In the RU-SKI study, 98 patients treated with first or second-generation TKI were included. Survival without MMR loss at 12 and 24 months after TKI discontinuation was 53% and 52%, respectively (38). An observational study by Gabriel Etienne et al exhibited MRFS rates of 51.8% and 43.8% at 12 and 60 months, respectively, similar to the RU-SKI study (39).…”

Section: Multiple Tkismentioning

confidence: 77%

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Treatment-Free Remission in Chronic Myeloid Leukemia and New Approaches by Targeting Leukemia Stem Cells

et al. 2021

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The therapeutic landscape for chronic myeloid leukemia (CML) has improved significantly with the approval of tyrosine kinase inhibitors (TKIs) for therapeutic use. Most patients with optimal responses to TKIs can have a normal life expectancy. Treatment-free remission (TFR) after discontinuing TKI has increasingly become a new goal for CML treatment. However, TKI only “control“ CML, and relapse after discontinuation has become a key factor hindering patient access to attempt TFR. In this study, we reviewed studies on TKI discontinuation, including both first and second-generation TKI. We also reviewed predictors of relapse, new monitoring methods, and strategies targeting leukemic stem cells.

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Section: Clinical Indicatorsmentioning

confidence: 62%

Section: Multiple Tkismentioning

confidence: 77%

Treatment-Free Remission in Chronic Myeloid Leukemia and New Approaches by Targeting Leukemia Stem Cells

et al. 2021

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“…75 Some patients, who underwent TFR, experienced withdrawal symptoms after stopping TKI therapy, including muscle and bone pain. [76][77][78] The symptoms usually lasted over months, beginning within days or weeks of drug discontinuation. However, the mechanisms underlying TKI withdrawal syndrome remain unclear.…”

Section: Issues Still To Be Consideredmentioning

confidence: 99%

Exploration of treatment‐free remission in CML, based on molecular monitoring

Zhang,

Zhou,

Zhou

et al. 2023

Cancer Medicine

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BackgroundTypical chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9; 22)(q34; q11) translocation. This chromosomal translocation forms the BCR::ABL1 fusion gene. The tyrosine kinase encoded by the BCR::ABL1 is considered to be the main pathogenic diver. BCR::ABL1 is not only a therapeutic target, but also a monitoring target. Monitoring of BCR::ABL1 reveals the progression of the disease and guides the next treatment. Now for CML, the target of treatment has been focused on treatment‐free remission (TFR).MethodsWe conducted a literature review of current developments of treatment‐free remission and molecular monitoring methods.ResultsMore effective and sensitive CML monitoring methods such as digital droplet PCR (ddPCR) and next generation sequencing (NGS) have further studied the measurable residual disease (MRD) and clonal heterogeneity, which provides strong support for the exploration of TFR. We discussed some of the factors that may be related to TFR outcomes at the molecular level, along with some monitoring strategies.ConclusionCurrently, predictive indicators for treatment‐free remission outcomes and recurrence are lacking in clinical practice. In future, treatment‐free remission research should focus on combining the clinical indicators with molecular monitoring and biological markers to personalize patient conditions and guide clinicians to develop individualized treatment plans, so that more patients with CML can achieve safer and stabler treatment‐free remission.

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“…In most cases, WS is mild and self‐limited, with a median duration of 6 months and generally not requiring treatment 18 . In a recent Russian prospective study, the WS rate was higher (42%), probably because retrospective analysis might underreport the incidence of low‐grade symptoms 71 . Nevertheless, clinicians should inform patients about the possibility of this event and the rare necessity to assume medications, such as anti‐inflammatory drugs or corticosteroids.…”

Section: Risks Associated With Tki Discontinuationmentioning

confidence: 99%

Tyrosine Kinase Inhibitor discontinuation in Chronic Myeloid Leukemia: eligibility criteria and predictors of success

Inzoli

Gambacorti‐Passerini

2022

American J Hematol

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TKI discontinuation proved to be safe and feasible in patients with CML with deep and durable molecular responses, introducing an additional treatment goal for these patients beyond overall survival. However, treatment interruption is a safe procedure only with appropriate patient selection and monitoring. Clinical and biological factors associated with better outcomes do not yet offer a precise stratification of patients according to their risk of relapse. This article aims at reviewing the leading studies present in the field in order to define eligibility criteria for discontinuation and predictors of success.

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Withdrawal Syndrome After Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI

Cited by 11 publications

References 25 publications

Treatment-Free Remission in Chronic Myeloid Leukemia and New Approaches by Targeting Leukemia Stem Cells

Treatment-Free Remission in Chronic Myeloid Leukemia and New Approaches by Targeting Leukemia Stem Cells

Exploration of treatment‐free remission in CML, based on molecular monitoring

Tyrosine Kinase Inhibitor discontinuation in Chronic Myeloid Leukemia: eligibility criteria and predictors of success

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