The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis

Franck E. Nicolini, Amr R. Ibrahim, Simona Soverini, Giovanni Martinelli, Martin C. Müller, Andreas Hochhaus, Inge H. Dufva, Dong Wook Kim, Jorge Cortes, Michael J. Mauro, Charles Chuah, Hélène Labussière, Stéphane Morisset, Catherine Roche-Lestienne, Eric Lippert, Sandrine Hayette, Senaka Peter, Wei Zhou, Véronique Maguer-Satta, Mauricette MichalletJohn Goldman, Jane F. Apperley, François Xavier Mahon, David Marin, Gabriel Etienne

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1510-1516
Number of pages7
JournalHaematologica
Volume98
Issue number10
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Matched-Pair Analysis
Protein-Tyrosine Kinases
Mutation
Survival
Homologous Transplantation
Kaplan-Meier Estimate
Survival Analysis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Proportional Hazards Models
Imatinib Mesylate
Chronic Disease
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis. / Nicolini, Franck E.; Ibrahim, Amr R.; Soverini, Simona; Martinelli, Giovanni; Müller, Martin C.; Hochhaus, Andreas; Dufva, Inge H.; Kim, Dong Wook; Cortes, Jorge; Mauro, Michael J.; Chuah, Charles; Labussière, Hélène; Morisset, Stéphane; Roche-Lestienne, Catherine; Lippert, Eric; Hayette, Sandrine; Peter, Senaka; Zhou, Wei; Maguer-Satta, Véronique; Michallet, Mauricette; Goldman, John; Apperley, Jane F.; Mahon, François Xavier; Marin, David; Etienne, Gabriel.

In: Haematologica, Vol. 98, No. 10, 01.10.2013, p. 1510-1516.

Research output: Contribution to journalArticle

Nicolini, FE, Ibrahim, AR, Soverini, S, Martinelli, G, Müller, MC, Hochhaus, A, Dufva, IH, Kim, DW, Cortes, J, Mauro, MJ, Chuah, C, Labussière, H, Morisset, S, Roche-Lestienne, C, Lippert, E, Hayette, S, Peter, S, Zhou, W, Maguer-Satta, V, Michallet, M, Goldman, J, Apperley, JF, Mahon, FX, Marin, D & Etienne, G 2013, 'The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis', Haematologica, vol. 98, no. 10, pp. 1510-1516. https://doi.org/10.3324/haematol.2012.080234
Nicolini, Franck E. ; Ibrahim, Amr R. ; Soverini, Simona ; Martinelli, Giovanni ; Müller, Martin C. ; Hochhaus, Andreas ; Dufva, Inge H. ; Kim, Dong Wook ; Cortes, Jorge ; Mauro, Michael J. ; Chuah, Charles ; Labussière, Hélène ; Morisset, Stéphane ; Roche-Lestienne, Catherine ; Lippert, Eric ; Hayette, Sandrine ; Peter, Senaka ; Zhou, Wei ; Maguer-Satta, Véronique ; Michallet, Mauricette ; Goldman, John ; Apperley, Jane F. ; Mahon, François Xavier ; Marin, David ; Etienne, Gabriel. / The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis. In: Haematologica. 2013 ; Vol. 98, No. 10. pp. 1510-1516.
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abstract = "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.",
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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

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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.

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