TY - JOUR
T1 - Chronic Myeloid Leukemia and Second-Generation Tyrosine Kinase Inhibitors
T2 - When, How, and Which One?
AU - Jabbour, Elias
AU - Kantarjian, Hagop
AU - Cortes, Jorge
PY - 2010/10
Y1 - 2010/10
N2 - Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse-event tolerance level, and risk factors.
AB - Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse-event tolerance level, and risk factors.
UR - http://www.scopus.com/inward/record.url?scp=77957096041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957096041&partnerID=8YFLogxK
U2 - 10.1053/j.seminhematol.2010.06.002
DO - 10.1053/j.seminhematol.2010.06.002
M3 - Article
C2 - 20875551
AN - SCOPUS:77957096041
SN - 0037-1963
VL - 47
SP - 344
EP - 353
JO - Seminars in hematology
JF - Seminars in hematology
IS - 4
ER -