scholarly journals Second‐ or third‐generation tyrosine kinase inhibitors in first‐line treatment of chronic myeloid leukemia in general population: Is there a real benefit?

2021 ◽  
Author(s):  
Jim Canet ◽  
Pascale Cony‐Makhoul ◽  
Sébastien Orazio ◽  
Edouard Cornet ◽  
Xavier Troussard ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
General Population ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Third Generation ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

scholarly journals Outcomes of Chronic Phase Chronic Myeloid Leukemia after Treatment with Multiple Tyrosine Kinase Inhibitors

2020 ◽  
Vol 9 (5) ◽  
pp. 1542
Author(s):  
Jee Hyun Kong ◽  
Elliott F. Winton ◽  
Leonard T. Heffner ◽  
Manila Gaddh ◽  
Brittany Hill ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Response ◽  
Line Treatment ◽  
First Line ◽  
Blastic Phase

We sought to evaluate the outcomes of chronic phase (CP) chronic myeloid leukemia (CML) in an era where five tyrosine kinase inhibitors (TKIs) are commercially available for the treatment of CML. Records of patients diagnosed with CP CML, treated with TKIs and referred to our center were reviewed. Between January 2005 and April 2016, 206 patients were followed for a median of 48.8 (1.4–190.1) months. A total of 76 (37%) patients received one TKI, 73 (35%) received two TKIs and 57 (28%) were exposed to >3 TKIs (3 TKIs, n = 33; 4 TKIs, n = 17; 5 TKIs, n = 7). Nineteen (9.2%) patients progressed to advanced phases of CML (accelerated phase, n = 6; myeloid blastic phase, n = 4; lymphoid blastic phase, n = 9). One third (n = 69) achieved complete molecular response (CMR) at first-line treatment. An additional 55 patients achieved CMR after second-line treatment. Twenty-five patients (12.1%) attempted TKI discontinuation and 14 (6.8%) stopped TKIs for a median of 6.3 months (range 1–53.4). The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs). The best OS was observed in patients tolerating and responding to first line TKI, but multiple TKIs led patients to gain treatment-free remission.

scholarly journals Cardiovascular Toxicities of Tyrosine Kinase Inhibitor in CML

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Samip R Master ◽  
Richard Preston Mansour
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Conflicts Of Interest ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
First Line Treatment

Background: Cardiovascular (CV) toxicity is a known toxicity of tyrosine kinase inhibitors (TKI) used for chronic myeloid leukemia (CML). Imatinib, dasatinib, nilotinib and bosutinib are all approved for first line treatment for CML. We did a retrospective analysis on adverse effects (AE) of TKIs that has been made available to public by the FDA. Methods: The FDA has made the data on AEs of various treatments available to general public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the CV AEs of various TKIs for the years 2017-2019. Results: The percentage of CV AE compared to total AEs reported for Imatinib, Dasatinib, Bosutinib , Nilotinib and Ponatinib were 7.2%, 10.5%, 15.8%, 23.4% and 23.5% respectively. The percentage of CV AE leading to death for Imatinib, Dasatinib, Bosutinib , Nilotinib and Ponatinib were 8.3%, 9.1%, 9.1%, 13.7 % and 18.6% respectively. Conclusions: Out of the reported cases of AEs to TKIs approved for front line CML, nilotinib appears to have more CV AE compared to imatinib, dasatinib and bolutinib. Imatinib appears to have least CV AE out of the total AEs reported Disclosures No relevant conflicts of interest to declare.

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