scholarly journals Imatinib—A New Tyrosine Kinase Inhibitor for First-Line Treatment of Chronic Myeloid Leukemia in 2015

JAMA Oncology ◽  
2015 ◽  
Vol 1 (2) ◽  
pp. 143 ◽  
Author(s):  
Carlo Gambacorti-Passerini ◽  
Rocco Piazza
Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Samip R Master ◽  
Richard Preston Mansour

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.


2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi

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.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2569-2569
Author(s):  
Nancy Cribb ◽  
Tazmin Merali ◽  
Bonnie MK Donato

Abstract Abstract 2569 Background: New treatment options in chronic myeloid leukemia (CML) have become available in the past years. However, there is a scarcity of published data documenting how patients are treated as well as the impact of the treatment of CP-CML in Canada. Objective: To describe current treatment patterns and clinical outcomes of CP-CML patients receiving treatment in Canada. Methods: Treatment data on CP-CML patients was extracted from a cancer patient treatment summary database, ONCO-CAPPS. The database is comprised of treatment summaries of over 12,000 Canadian cancer patients from across the country. For the study, CP-CML patients aged 18 years or older, who received 400mg of imatinib as 1st-line treatment, and who completed at least 4 continuous weeks of this treatment between October 1, 2008 and December 31, 2009, were eligible for study inclusion. Results: A total of 301 patients met the selection criteria. At the time of review, 62% of patients had a confirmed diagnosis of CP-CML for 2 years or more. Of the CP-CML patients in the study who were prescribed 400mg of imatinib as their initial CP-CML treatment, 51% (155/301) received a 2nd line treatment option, either a dose modification or a change of therapy. Of those requiring 2nd line treatment, 32% (50/155) of patients received an increase in their imatinib dose, resulting in an average daily dose of 664 mg, and representing a 66% increase in the dose of imatinib. Average response times for patients who received an increase in imatinib dose for Complete Hematological Response (CHR) was 183 days, for Complete Cytogenetic Response (CCyR) was 671 days, and for Major Molecular Response (MMR) was 971 days. These response times exceed both Canadian Consensus Guidelines as well as the 2009 ELN (European Leukemia Network) recommendations. Furthermore, 45% (69/155) of patients receiving a 2nd line CML treatment experienced intolerance to imatinib 400 mg resulting in dose decrease or treatment interruption. Switching to second generation tyrosine kinase inhibitor agents (dasatinib or nilotinib) due to inadequate response, loss of response or intolerance to imatinib occurred in 20% of the population. Conclusions: Analysis of Canadian patients over time revealed that 51% of CP-CML patients initiated on 400mg imatinib received 2nd line treatment. The most frequent modification was due to intolerance. Of note, 32% received a dose escalation, which was more common than switching to a second generation tyrosine kinase inhibitor. Furthermore, response times observed amongst patients in this study whose imatinib dose was escalated exceeded timelines for treatment response determination as noted in both internationally and locally recognized treatment guidelines. Published research demonstrates that delays in achieving response are associated with increased risk of progression among patients with CML. Disclosures: Cribb: Drug Intelligence Inc.: Research Funding. Merali:Bristol-Myers Squibb Canada: Research Funding. Donato:Drug Intelligence Inc.: Research Funding.


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