Successful use of long-term follow-up in patients with chronic myeloid leukemia with a deep molecular response at reduced doses of 2nd generation tyrosine kinase inhibitors: clinical cases and literature review

2020 ◽  
Vol 92 (7) ◽  
pp. 90-94
Author(s):  
M. A. Gurianova ◽  
E. Yu. Chelysheva ◽  
O. A. Shukhov ◽  
A. G. Turkina
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Molecular Response ◽  
Long Term Treatment ◽  
Deep Molecular Response

Therapy with tyrosine kinase inhibitors (TKI) allows to achieve a deep molecular response in 6070% of patients with chronic myeloid leukemia (CML). According to the current guidelines CML patients receive a long-term treatment with TKI in standard dose. The frequently observed adverse effects (AE) of TKI therapy are mostly dose-dependent. A new treatment approach with TKI use in reduced dose is desirable for the CML patients with existing AE or with a high risk of AE occurrence. We report the two cases of successful long-term treatment of CML patients with reduced doses of second generation TKIs. The aim of the TKI dose reduction was to reduce the clinical manifestations of drug toxicities and to prevent the AE.

scholarly journals BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia

2017 ◽  
Vol 24 (6) ◽  
pp. 433-452 ◽  
Author(s):  
Sandra Cuellar ◽  
Michael Vozniak ◽  
Jill Rhodes ◽  
Nicholas Forcello ◽  
Daniel Olszta
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Patient Centered ◽  
Long Term Treatment

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug–drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug–drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug–drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist–patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

scholarly journals Early Dynamics of Chronic Myeloid Leukemia on Nilotinib Predicts Deep Molecular Response

2021 ◽  
Author(s):  
Yuji Okamoto ◽  
Mitsuhito Hirano ◽  
Kai Morino ◽  
Masashi K. Kajita ◽  
Shinji Nakaoka ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Myeloproliferative Disorder ◽  
Initial Time ◽  
Molecular Response ◽  
Early Prediction ◽  
Deep Molecular Response

AbstractChronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase1,2. ABL1-selective tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML3–7. The ultimate goal of CML treatment is likely to be TKI-free maintenance of deep molecular response (DMR), which is defined by quantitative measurement of BCR-ABL1 transcripts on the international scale (IS)8, and durable DMR is a prerequisite to reach this goal9. Thus, an algorithm to enable the early prediction of DMR achievement on TKI therapy is quite valuable. Here, we show that our mathematical framework based on a clinical trial dataset10 can accurately predict the response to frontline nilotinib. We found that our simple dynamical model can predict nilotinib response by using two common laboratory findings (observation values): IS11,12 and white blood cell (WBC) count. Furthermore, our proposed method identified patients who failed to achieve DMR with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs in clinical practice.Significance StatementChronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. The goal of this treatment is the sequential achievement of deep molecular response (DMR). Tyrosine kinase inhibitors (TKIs) are effective in the reduction because they inhibit CML cell proliferation. However, because of individual differences in the TKI efficacy, some patients are unable to achieve DMR, so that early prediction of DMR reachability is necessary for personalized medicine. By combining time series analysis and mathematical modeling, we developed a mathematical method that accurately predicts patients who do not achieve DMR in the early stages of TKI administration. Our prediction method gives a basis of effective personalized treatments for CML patients.

scholarly journals Biological Mechanisms of Sustaining Deep Molecular Response in Chronic Myeloid Leukemia Upon Withdrawal of Tyrosine Kinase Inhibitors

2021 ◽  
Vol 14 (4) ◽  
pp. 427-435
Author(s):  
Ekaterina Yurevna Chelysheva ◽  
M.A. Guryanova ◽  
A.G. Turkina
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Molecular Response ◽  
Biological Mechanisms ◽  
Deep Molecular Response ◽  
Cell Proliferation Control

The feasibility of treatment-free follow-up in chronic myeloid leukemia (CML) patients is an important issue in the era of tyrosine kinase inhibitors (TKI). The clinical trials of TKI withdrawal in case of a stable deep molecular response prove the probability of sustaining molecular remission in 40-60 % of patients. Treatment-free remission (TFR), even under persistence of residual leukemia cells, suggests that there are special biologically determined mechanisms of tumor cell proliferation control, which are independent of BCR-ABL kinase activity. The search for factors determining differences in residual leukemia clone kinetics upon TKI withdrawal is an objective which is crucial for understanding TFR as a new biological phenomenon. The review provides worldwide evidence dealing with the study of immunological, genetic, and other biological mechanisms underlying the control of minimal residual disease upon TKI discontinuation in CML patients.

scholarly journals Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 243-247
Author(s):  
Delphine Rea
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Treatment Free Remission

Abstract The paradigm for managing patients with chronic myeloid leukemia is evolving. In the recent past, restoring a normal life expectancy while patients are receiving never-ending targeted therapy with BCR–ABL1 tyrosine kinase inhibitors through prevention of progression to blast phase and mitigation of iatrogenic risks was considered the best achievable outcome. Now, long-term treatment-free remission with continued response off tyrosine kinase inhibitor therapy is recognized as the most optimal benefit of treatment. Indeed, numerous independent clinical trials provided solid proof that tyrosine kinase inhibitor discontinuation was feasible in patients with deep and sustained molecular responses. This article discusses when tyrosine kinase inhibitors may be safely stopped in clinical practice on the basis of the best and latest available evidence.

Sign in / Sign up

Export Citation Format

Share Document