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

Chen, Yilin; Zhao, Hong; Guo, Jing-Ming; Zou, Jing; He, Wenjuan; Han, Danlei; Cheng, Fanjun

doi:10.3389/fphar.2023.1101743

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…A recent report by Goni et al recruited 26 CML patients on generic imatinib for ≥3 years and in sustained deep molecular response, where the median follow-up was 33 months, and 42.3% continued to be in TFR, with all patients who restarted on generic imatinib regaining a major molecular response [58]. A similar approach in 190 CML Chinese patients enrolled in the TFR protocol showed a success rate of 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 after stopping TKI, and 98.2% of patients who needed to restart TKI treatment quickly achieved MMR [59]. In a retrospective analysis of 168 CML patients recruited for the TFR protocol, 112 of the patients were treated with imatinib and 56 with second-generation TKIs, and 73.2% maintained MR 4 .…”

Section: Discussionmentioning

confidence: 99%

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study

Marin,

Wosniaki,

Sanchuki

et al. 2023

IJMS

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Chronic myeloid leukemia (CML) is a well-characterized oncological disease in which virtually all patients possess a translocation (9;22) that generates the tyrosine kinase BCR::ABL1 protein. This translocation represents one of the milestones in molecular oncology in terms of both diagnostic and prognostic evaluations. The molecular detection of the BCR::ABL1 transcription is a required factor for CML diagnosis, and its molecular quantification is essential for assessing treatment options and clinical approaches. In the CML molecular context, point mutations on the ABL1 gene are also a challenge for clinical guidelines because several mutations are responsible for tyrosine kinase inhibitor resistance, indicating that a change may be necessary in the treatment protocol. So far, the European LeukemiaNet and the National Comprehensive Cancer Network (NCCN) have presented international guidelines on CML molecular approaches, especially those related to BCR::ABL1 expression. In this study, we show almost three years’ worth of data regarding the clinical treatment of CML patients at the Erasto Gaertner Hospital, Curitiba, Brazil. These data primarily comprise 155 patients and 532 clinical samples. BCR::ABL1 quantification by a duplex-one-step RT-qPCR and ABL1 mutations detection were conducted. Furthermore, digital PCR for both BCR::ABL1 expression and ABL1 mutations were conducted in a sub-cohort. This manuscript describes and discusses the clinical importance and relevance of molecular biology testing in Brazilian CML patients, demonstrating its cost-effectiveness.

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Section: Discussionmentioning

confidence: 99%

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study

Marin,

Wosniaki,

Sanchuki

et al. 2023

IJMS

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“…With a median follow-up after stopping TKI treatment of 17 months, the estimated TFR were 76.9%, 68.8%, and 65.5% at 6, 12, and 24 months. 29 …”

Section: Tki Discontinuation and Tfrmentioning

confidence: 99%

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient

Russo,

Malagola,

Polverelli

et al. 2023

Therapeutic Advances in Hematology

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The introduction of imatinib in 2000 opened the era of tyrosine kinase inhibitors (TKIs) for CML therapy and has revolutionized the life expectancy of CML patients, which is now quite like the one of the healthy aged population. Over the last 20 years, both the TKI therapy itself and the objectives have undergone evolutions highlighted and discussed in this review. The main objective of the CML therapy in the first 10 years after TKI introduction was to abolish the disease progression from the chronic to the blastic phase and guarantee the long-term survival of the great majority of patients. In the second 10 years (from 2010 to the present), the main objective of CML therapy moved from survival, considered achieved as a goal, to treatment-free remission (TFR). Two phenomena emerged: no more than 50–60% of CML patients could be candidates for discontinuation and over 50% of them molecularly relapse. The increased cumulative incidence of specific TKI off-target side effects was such relevant to compel to discontinue or reduce the TKI administration in a significant proportion of patients and to avoid a specific TKI in particular settings of patients. Therefore, the treatment strategy must be adapted to each category of patients. What about the patients who do not get or fail the TFR? Should they be compelled to continue the TKIs at the maximum tolerated dose? Alternative strategies based on the principle of minimal effective dose have been tested with success and they are now re-evaluated with more attention, since they guarantee survival and probably a better quality of life, too. Moving from treating the disease to treating the patient is an important change of paradigm. We can say that we are entering a personalized CML therapy, which considers the patients’ age, their comorbidities, tolerability, and specific objectives. In this scenario, the new techniques supporting the monitoring of the patients, such as the digital PCR, must be considered. In the present review, we present in deep this evolution and comment on the future perspectives of CML therapy.

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Treatment‐free remission as a new goal in the management of chronic myeloid leukemia: Clinical and biological aspects

Cattaneo,

Bucelli,

Bellani

et al. 2024

Hematological Oncology

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The therapeutic armamentarium of chronic myeloid leukemia (CML) has dramatically improved after small molecule tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 became available, with a life expectancy now close to that of the general population. Although highly effective, these drugs also have a toxicity profile that is often mild to moderate, but sometimes severe. Indeed, long‐term treatment with TKIs can lead to chronic adverse events that can negatively affect patients' quality of life and can promote significant morbidity and mortality, particularly in the case of second‐ or third‐generation TKIs. Treatment discontinuation has therefore become an emerging goal for CML patients and numerous studies have evaluated in off‐TKI subjects what requirements are appropriate for an attempt at treatment‐free remission (TFR). TFR eligibility is currently limited to a small population of subjects with both deep and sustained molecular responses to TKIs. For those attempting TFR, average success rates are promising, with 25%–30% of patients experiencing prolonged TFR. In case of failure to maintain sustained TFR, safety results to date are reassuring, with almost all patients responding successfully to resumption of TKIs, and advanced‐phase disease progression representing a very rare event. The purpose of this review is to discuss guidelines for TKI discontinuation, clinical advances from clinical trials and real‐life experiences, and describe areas of research, particularly regarding the biological factors capable of predicting the success of TFR.

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

Cited by 4 publications

References 34 publications

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient

Treatment‐free remission as a new goal in the management of chronic myeloid leukemia: Clinical and biological aspects

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