Comment on low‐dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment‐free remission in chronic myeloid leukemia patients: Results of a retrospective study

Cancer ◽  
2020 ◽  
Author(s):  
Leonardo Campiotti ◽  
Matteo B. Suter ◽  
Francesco Dentali
Keyword(s):  
Retrospective Study ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Kinase Inhibitors ◽  
Treatment Discontinuation ◽  
Treatment Free Remission

Sustained molecular response in chronic myeloid leukemia deep responders treated with low dose tyrosine kinase inhibitors

2017 ◽  
Vol 59 (3) ◽  
pp. 766-769 ◽  
Author(s):  
Emilie Cayssials ◽  
Florence Tartarin ◽  
Joëlle Guilhot ◽  
Nathalie Sorel ◽  
Jean Claude Chomel ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Kinase Inhibitors ◽  
Molecular Response

scholarly journals Tyrosine kinase inhibitors and pregnancy in chronic myeloid leukemia: opinion, evidence, and recommendations

2020 ◽  
Vol 11 ◽  
pp. 204062072096612
Author(s):  
Elisabetta Abruzzese ◽  
Michael Mauro ◽  
Jane Apperley ◽  
Ekaterina Chelysheva
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Disease Burden ◽  
Kinase Inhibitors ◽  
Position Paper ◽  
Therapeutic Interventions ◽  
Therapy Discontinuation ◽  
Treatment Free Remission

With survival expectation that of age-matched controls and given excellent response and worldwide access to tyrosine kinase inhibitors (TKI), family planning is increasingly important for a considerable fraction of patients with chronic myeloid leukemia (CML). The potential for therapy discontinuation (“treatment free remission”) can afford the opportunity for a CML patient in deep response to plan and carry a pregnancy to full term without any therapeutic interventions. However, the reality of pregnancy desired or occurring when patients are not eligible for treatment-free remission raises the discussion of therapy choices during pregnancy. To date there are no official guidelines available to assist patients and clinicians with these decisions. This first position paper aims to analyze information published and presented surrounding this challenging area, with focus on different scenarios of disease burden and time from CML diagnosis, including CML discovered during pregnancy and pregnancy during CML treatment. An updated review, supported by data and presented together with authors’ joint recommendations, is aimed to counsel the practical management of CML patients and pregnancy.

scholarly journals DYRK2 controls a key regulatory network in chronic myeloid leukemia stem cells

2020 ◽  
Vol 52 (10) ◽  
pp. 1663-1672
Author(s):  
Chun Shik Park ◽  
H. Daniel Lacorazza
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Stem Cell Population ◽  
Leukemia Stem Cells ◽  
Treatment Free Remission

Abstract Chronic myeloid leukemia is a hematological cancer driven by the oncoprotein BCR-ABL1, and lifelong treatment with tyrosine kinase inhibitors extends patient survival to nearly the life expectancy of the general population. Despite advances in the development of more potent tyrosine kinase inhibitors to induce a durable deep molecular response, more than half of patients relapse upon treatment discontinuation. This clinical finding supports the paradigm that leukemia stem cells feed the neoplasm, resist tyrosine kinase inhibition, and reactivate upon drug withdrawal depending on the fitness of the patient’s immune surveillance. This concept lends support to the idea that treatment-free remission is not achieved solely with tyrosine kinase inhibitors and that new molecular targets independent of BCR-ABL1 signaling are needed in order to develop adjuvant therapy to more efficiently eradicate the leukemia stem cell population responsible for chemoresistance and relapse. Future efforts must focus on the identification of new targets to support the discovery of potent and safe small molecules able to specifically eradicate the leukemic stem cell population. In this review, we briefly discuss molecular maintenance in leukemia stem cells in chronic myeloid leukemia and provide a more in-depth discussion of the dual-specificity kinase DYRK2, which has been identified as a novel actionable checkpoint in a critical leukemic network. DYRK2 controls the activation of p53 and proteasomal degradation of c-MYC, leading to impaired survival and self-renewal of leukemia stem cells; thus, pharmacological activation of DYRK2 as an adjuvant to standard therapy has the potential to induce treatment-free remission.

Optimizing patient selection for treatment-free remission

2020 ◽  
Vol 26 (5) ◽  
pp. 1220-1224
Author(s):  
Caitlin R Rausch ◽  
Shilpa Paul
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Heterogeneous Data ◽  
Healthy Population ◽  
Molecular Response ◽  
Treatment Free Remission

The advent of BCR–ABL1 tyrosine kinase inhibitors has revolutionized the treatment and prognosis of chronic myeloid leukemia. Life expectancy for patients with chronic phase chronic myeloid leukemia now nears that of the healthy population; however, optimal outcomes require continuous tyrosine kinase inhibitor administration, which can impact patient quality of life. Consequently, the concept of treatment-free remission has been explored in patients achieving and sustaining a deep molecular response. Heterogeneous data exist with multiple tyrosine kinase inhibitors; however, nilotinib is currently the only therapy that has been approved by the US Food and Drug Administration for treatment-free remission. The decision to pursue treatment-free remission is one that relies heavily on both patient- and disease-related factors. Herein, we will discuss relevant considerations to be made when determining an optimal candidate for treatment-free remission.

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