Prolonged treatment-free remission in chronic myeloid leukemia patients with previous <i>BCR-ABL1</i> kinase domain mutations

Claudiani, Simone; Apperley, Jane F.; Khan, Afzal; Khorashad, Jamshid S.; Milojković, Dragana

doi:10.3324/haematol.2019.234179

Cited by 8 publications

(12 citation statements)

References 13 publications

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“…However, in one small-scale study, of the 10 patients who discontinued TKI treatment (9 of which had detectable mutations, including T315I), 5 maintained TFR [66]. Therefore, whether patients with a previously reported BCR::ABL1 kinase domain mutation can maintain TFR and thus safely make a TKI discontinuation attempt remains to be confirmed by larger studies.…”

Section: Bcr::abl1 Kinase Domain Mutationsmentioning

confidence: 99%

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

2022

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Purpose of Review Clinical factors alone do not enable us to differentiate which patients will maintain treatment-free remission (TFR) from those who are likely to relapse. Thus, patient-specific factors must also play a role. This review will update the reader on the most recent studies presenting biological factors that can help predict tyrosine kinase inhibitor (TKI) discontinuation success. Recent Findings Cellular and molecular factors with a suggested role in TFR include immune factors and leukemic stem cell (LSC) persistence; the BCR::ABL1 transcript type, halving time, and BCR::ABL1 DNA and RNA positivity; as well as other molecular factors such as somatic mutations, RNA expression, and telomere length. Summary Our review presents several biomarkers with predictive value for TFR but also highlights areas of unmet need. Future discontinuation guidelines will likely include biological factors for the personalization of TFR prediction. However, it will be important that such advances do not prevent more patients from making a TKI discontinuation attempt.

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Section: Bcr::abl1 Kinase Domain Mutationsmentioning

confidence: 99%

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

2022

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“…51,136,137 Other possible markers include regulatory T cells, cytotoxic CD8+ T lymphocyte (CTL), and somatic mutations. 134,[138][139][140] Type of BCR-ABL1 transcript also has a role; in a study by D'Adda et al, TFR maintenance was observed to be higher in CML patients with e14a2 transcript when compared with e13a2 transcripts. 141 However, all of these biomarkers are not readily available for routine clinical use, and thus, clinical parameters remain the most widely used or accessible parameters for TFR.…”

Section: Predictors and Biomarkers For Tfrmentioning

confidence: 99%

Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review

Rinaldi¹,

Winston²

2023

JBM

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Chronic myeloid leukemia (CML) is one of the most common leukemias occurring in the adult population. The course of CML is divided into three phases: the chronic phase, the acceleration phase, and the blast phase. Pathophysiology of CML revolves around Philadelphia chromosome that constitutively activate tyrosine kinase through BCR-ABL1 oncoprotein. In the era of tyrosine kinase inhibitors (TKIs), CML patients now have a similar life expectancy to people without CML, and it is now very rare for CML patients to progress to the blast phase. Only a small proportion of CML patients have resistance to TKI, caused by BCR-ABL1 point mutations. CML patients with TKI resistance should be treated with second or third generation TKI, depending on the BCR-ABL1 mutation. Recently, many studies have shown that it is possible for CML patients who achieve a long-term deep molecular response to stop TKIs treatment and maintain remission. This review aimed to provide an overview of CML, including its pathophysiology, clinical manifestations, the role of stem cells, CML treatments, and treatment-free remission.

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“…94 The authors speculated that if a patient with a BCR::ABL1 mutation promptly receives an effective alternative TKI and a DMR is achieved and maintained, the adverse outcomes associated with BCR::ABL1 mutations can be overcome. 93 Patient 3, a case of early treatment failure A 37-year-old female was diagnosed with CML in 2013 and received nilotinib as first-line therapy in a clinical trial. The transcript was e14a2/e13a2, the ELTS score was intermediate and there were no additional chromosome abnormalities at diagnosis.…”

Section: Patient 2 a Case Of Non-adherence And Late Acquisition Of Bc...mentioning

confidence: 99%

“…21 Claudiani and colleagues assessed ten patients with previous BCR::ABL1 mutations who stopped TKI due to intolerance. 93 All had maintained MR4 for at least 1 year prior to stopping TKI (median 6.3 years) and the median duration of TKI therapy before stopping was 13 years. The molecular relapse-free survival for the ten patients was 50% with 1 to 4.7 years of follow-up.…”

Section: Case Scenariosmentioning

confidence: 99%

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Measurable residual disease in chronic myeloid leukemia

Branford

Apperley

2022

haematol

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Chronic myeloid leukemia is characterized by a single genetic abnormality resulting in a fusion gene whose mRNA product is easily detected and quantified by reverse-transcriptase polymerase chain reaction analysis. Measuring residual disease was originally introduced to identify patients relapsing after allogeneic stem cell transplantation but rapidly adopted to quantify responses to tyrosine kinase inhibitors. Real-time quantitative polymerase chain reaction is now an essential tool for the management of patients and is used to influence treatment decisions. In this review we track this development including the international collaboration to standardize results, discuss the integration of molecular monitoring with other factors that affect patients’ management, and describe emerging technology. Four case histories describe varying scenarios in which the accurate measurement of residual disease identified patients at risk of disease progression and allowed appropriate investigations and timely clinical intervention.

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Prolonged treatment-free remission in chronic myeloid leukemia patients with previous BCR-ABL1 kinase domain mutations

Cited by 8 publications

References 13 publications

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review

Measurable residual disease in chronic myeloid leukemia

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