TY - JOUR
T1 - Chronic myeloid leukemia in the tyrosine kinase inhibitor era
T2 - What is the "best" therapy?
AU - Agrawal, Meetu
AU - Garg, Ravin J.
AU - Kantarjian, Hagop
AU - Cortes, Jorge
N1 - Funding Information:
Disclosure Drs. Cortes and Kantarjian both have research support from Novartis, BMS, and Pfizer.
PY - 2010/9
Y1 - 2010/9
N2 - The introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myeloid leukemia (CML). By directly targeting the Bcr-Abl kinase, imatinib leads to durable cytogenetic remissions and in turn improved survival. However, many patients with CML develop resistance, fail to respond, or become intolerant to imatinib due to side effects. This has spurred interest in developing second-generation TKIs to overcome the mechanisms of resistance that lead to treatment failure, specifically Bcr-Abl1 kinase domain mutations. Two second-generation TKIs, nilotinib and dasatinib, are approved for the treatment of CML after imatinib failure or intolerance. Unfortunately, many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T315I. Various other strategies are now in use to optimize the treatment of CML, including dose optimization of imatinib, combination therapy, upfront use of second-generation TKIs, and use of maintenance therapy with interferon-α and vaccines. This review highlights progress made in the treatment of CML in the past year.
AB - The introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myeloid leukemia (CML). By directly targeting the Bcr-Abl kinase, imatinib leads to durable cytogenetic remissions and in turn improved survival. However, many patients with CML develop resistance, fail to respond, or become intolerant to imatinib due to side effects. This has spurred interest in developing second-generation TKIs to overcome the mechanisms of resistance that lead to treatment failure, specifically Bcr-Abl1 kinase domain mutations. Two second-generation TKIs, nilotinib and dasatinib, are approved for the treatment of CML after imatinib failure or intolerance. Unfortunately, many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T315I. Various other strategies are now in use to optimize the treatment of CML, including dose optimization of imatinib, combination therapy, upfront use of second-generation TKIs, and use of maintenance therapy with interferon-α and vaccines. This review highlights progress made in the treatment of CML in the past year.
KW - Chronic myeloid leukemia
KW - Dasatinib
KW - Imatinib
KW - Nilotinib
UR - http://www.scopus.com/inward/record.url?scp=77956265263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956265263&partnerID=8YFLogxK
U2 - 10.1007/s11912-010-0116-1
DO - 10.1007/s11912-010-0116-1
M3 - Review article
C2 - 20640942
AN - SCOPUS:77956265263
SN - 1523-3790
VL - 12
SP - 302
EP - 313
JO - Current Oncology Reports
JF - Current Oncology Reports
IS - 5
ER -