TY - JOUR
T1 - Clinical Algorithms for the Treatment of Patients With Chronic Myeloid Leukemia
T2 - The 2010 Perspective
AU - Jabbour, Elias
AU - Fullmer, Amber
AU - Cortés, Jorge E.
AU - Kantarjian, Hagop
N1 - Funding Information:
Dr. Jabbour has served on a Speaker's Bureau for Bristol-Myers Squibb Company and Novartis Pharmaceuticals Corporation. Dr. Fullmer has no relevant relationships to disclose. Dr. Cort?s has no relevant relationships to disclose. Dr. Kantarjian has received research funding from Bristol-Myers Squibb Company, Novartis Pharmaceuticals Corporation, and Wyeth Pharmaceuticals. This article includes discussion of investigational and/or unlabeled uses of drugs, including the use of first-line dasatinib or nilotinib, bosutinib, AP24534, and omacetaxine mepesuccinate in chronic myeloid leukemia.
Funding Information:
Dr. Kantarjian has received research funding from Bristol-Myers Squibb Company, Novartis Pharmaceuticals Corporation, and Wyeth Pharmaceuticals.
PY - 2010/6
Y1 - 2010/6
N2 - Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph) that results in the synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase (TK). The introduction of imatinib, a TK 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 because of toxicity (intolerance). In patients for whom standard-dose imatinib therapy (400 mg/day) fails, imatinib dose escalation (600-800 mg/day) 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 pharmacologic 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 hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph) that results in the synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase (TK). The introduction of imatinib, a TK 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 because of toxicity (intolerance). In patients for whom standard-dose imatinib therapy (400 mg/day) fails, imatinib dose escalation (600-800 mg/day) 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 pharmacologic 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.
KW - AP24534
KW - BCR-ABL
KW - Bosutinib
KW - Dasatinib
KW - Imatinib
KW - Nilotinib
KW - Omacetaxine
UR - http://www.scopus.com/inward/record.url?scp=77957357810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957357810&partnerID=8YFLogxK
U2 - 10.3816/CLML.2010.s.001
DO - 10.3816/CLML.2010.s.001
M3 - Article
C2 - 20529808
AN - SCOPUS:77957357810
SN - 2152-2650
VL - 10
SP - S6-S13
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -