TY - JOUR
T1 - The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis
AU - Nicolini, Franck E.
AU - Ibrahim, Amr R.
AU - Soverini, Simona
AU - Martinelli, Giovanni
AU - Müller, Martin C.
AU - Hochhaus, Andreas
AU - Dufva, Inge H.
AU - Kim, Dong Wook
AU - Cortes, Jorge
AU - Mauro, Michael J.
AU - Chuah, Charles
AU - Labussière, Hélène
AU - Morisset, Stéphane
AU - Roche-Lestienne, Catherine
AU - Lippert, Eric
AU - Hayette, Sandrine
AU - Peter, Senaka
AU - Zhou, Wei
AU - Maguer-Satta, Véronique
AU - Michallet, Mauricette
AU - Goldman, John
AU - Apperley, Jane F.
AU - Mahon, François Xavier
AU - Marin, David
AU - Etienne, Gabriel
PY - 2013/10/1
Y1 - 2013/10/1
N2 - The BCR-ABL T315I mutation confers resistance to currently licensed tyrosine kinase inhibitors in chronic myelogenous leukemia. However, the impact of this mutation on survival in early stages of disease, in chronic phase, has never been detailed. Using matched pair analysis, a cohort of 64 patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for T315I+ patients versus not reached for T315I- ones; P=0.006) and failure-free survival (since imatinib-resistance: 34.7 months for T315I+ patients versus not reached for T315I- patients; P=0.003). In addition, Cox proportional hazard models adjusted on overall survival demonstrated the negative influence of the T315I mutation (P=0.02, HR=2.54). These results confirm early assumptions concerning the poor prognosis of chronic phase chronic myelogenous leukemia patients with the T315I mutation who are not eligible for allogeneic transplantation, and demonstrate the need for more therapeutic options.
AB - The BCR-ABL T315I mutation confers resistance to currently licensed tyrosine kinase inhibitors in chronic myelogenous leukemia. However, the impact of this mutation on survival in early stages of disease, in chronic phase, has never been detailed. Using matched pair analysis, a cohort of 64 patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for T315I+ patients versus not reached for T315I- ones; P=0.006) and failure-free survival (since imatinib-resistance: 34.7 months for T315I+ patients versus not reached for T315I- patients; P=0.003). In addition, Cox proportional hazard models adjusted on overall survival demonstrated the negative influence of the T315I mutation (P=0.02, HR=2.54). These results confirm early assumptions concerning the poor prognosis of chronic phase chronic myelogenous leukemia patients with the T315I mutation who are not eligible for allogeneic transplantation, and demonstrate the need for more therapeutic options.
UR - http://www.scopus.com/inward/record.url?scp=84884911671&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884911671&partnerID=8YFLogxK
U2 - 10.3324/haematol.2012.080234
DO - 10.3324/haematol.2012.080234
M3 - Article
C2 - 23716543
AN - SCOPUS:84884911671
SN - 0390-6078
VL - 98
SP - 1510
EP - 1516
JO - Haematologica
JF - Haematologica
IS - 10
ER -