TY - JOUR
T1 - A critical review of trials of first-line BCR-ABL inhibitor treatment in patients with newly diagnosed chronic myeloid leukemia in chronic phase
AU - Jabbour, Elias
AU - Lipton, Jeffrey H.
N1 - Funding Information:
The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and medical expertise. The authors acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing and editing support. Bristol-Myers Squibb did not influence the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript.
PY - 2013/12
Y1 - 2013/12
N2 - Background The characteristic expression of the constitutively active oncoprotein, BCR-ABL tyrosine kinase, in chronic myeloid leukemia (CML) was the basis for the development of BCR-ABL tyrosine kinase inhibitors for treatment. Three BCR-ABL inhibitors, imatinib, nilotinib, and dasatinib, have been approved by the US Food and Drug Administration for first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Methods This article reviews the key phase III clinical trials supporting the use of first-line imatinib, nilotinib, and dasatinib in patients with CML-CP, as well as findings of supportive phase II studies. Results At the time of its approval in 2001, imatinib induced unprecedented response rates in patients with CML-CP; however, resistance and intolerance to imatinib prevent 20% to 30% of patients from deriving full therapeutic benefit. Nilotinib and dasatinib, both approved in 2010 for first-line CML-CP treatment, are more potent than imatinib and less susceptible to imatinib resistance mechanisms. Comparative clinical trials of each agent with imatinib have shown that they are associated with significantly deeper and more rapid responses than standard-dose imatinib, without compromising safety. Conclusions Given that evidence suggests achievement of an early response is predictive of improved long-term outcomes, earlier use of these compounds may lead to more rapid, deeper responses corresponding with improvements in patient outcome. Although future studies will benefit from more uniform definitions of end points and methods of analysis, data from published studies of first-line BCR-ABL inhibitor treatment for patients with newly diagnosed CML-CP support the use of dasatinib or nilotinib in place of imatinib.
AB - Background The characteristic expression of the constitutively active oncoprotein, BCR-ABL tyrosine kinase, in chronic myeloid leukemia (CML) was the basis for the development of BCR-ABL tyrosine kinase inhibitors for treatment. Three BCR-ABL inhibitors, imatinib, nilotinib, and dasatinib, have been approved by the US Food and Drug Administration for first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Methods This article reviews the key phase III clinical trials supporting the use of first-line imatinib, nilotinib, and dasatinib in patients with CML-CP, as well as findings of supportive phase II studies. Results At the time of its approval in 2001, imatinib induced unprecedented response rates in patients with CML-CP; however, resistance and intolerance to imatinib prevent 20% to 30% of patients from deriving full therapeutic benefit. Nilotinib and dasatinib, both approved in 2010 for first-line CML-CP treatment, are more potent than imatinib and less susceptible to imatinib resistance mechanisms. Comparative clinical trials of each agent with imatinib have shown that they are associated with significantly deeper and more rapid responses than standard-dose imatinib, without compromising safety. Conclusions Given that evidence suggests achievement of an early response is predictive of improved long-term outcomes, earlier use of these compounds may lead to more rapid, deeper responses corresponding with improvements in patient outcome. Although future studies will benefit from more uniform definitions of end points and methods of analysis, data from published studies of first-line BCR-ABL inhibitor treatment for patients with newly diagnosed CML-CP support the use of dasatinib or nilotinib in place of imatinib.
KW - Dasatinib
KW - Imatinib
KW - Nilotinib
KW - Outcomes
KW - Response
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U2 - 10.1016/j.clml.2013.05.012
DO - 10.1016/j.clml.2013.05.012
M3 - Review article
C2 - 24095296
AN - SCOPUS:84887991063
SN - 2152-2650
VL - 13
SP - 646
EP - 656
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 6
ER -