BCR-ABL Mutations in Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors and Impact on Survival

Katia Borgia Barbosa Pagnano; Israel Bendit; Carla Boquimpani; Carmino Antonio De Souza; Eliana C.M. Miranda; Ilana Zalcberg; Irene Larripa; Luciana Nardinelli; Rosana Antunes Silveira; Laura Fogliatto; Nelson Spector; Vaneuza Funke; Ricardo Pasquini; Vania Hungria; Carlos Sérgio Chiattone; Nelma Clementino; Monika Conchon; Elena Beatriz Moiraghi; Jose Luis Lopez; Carolina Pavlovsky; Miguel A. Pavlovsky; Eduardo E. Cervera; Luis Antonio Meillon; Belinda Simões; Nelson Hamerschlak; Alicia Helena Magarinos Bozzano; Ernesto Mayta; Jorge Cortes; Raquel M. Bengió

doi:10.3109/07357907.2015.1065499

BCR-ABL Mutations in Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors and Impact on Survival

Katia Borgia Barbosa Pagnano, Israel Bendit, Carla Boquimpani, Carmino Antonio De Souza, Eliana C.M. Miranda, Ilana Zalcberg, Irene Larripa, Luciana Nardinelli, Rosana Antunes Silveira, Laura Fogliatto, Nelson Spector, Vaneuza Funke, Ricardo Pasquini, Vania Hungria, Carlos Sérgio Chiattone, Nelma Clementino, Monika Conchon, Elena Beatriz Moiraghi, Jose Luis Lopez, Carolina PavlovskyMiguel A. Pavlovsky, Eduardo E. Cervera, Luis Antonio Meillon, Belinda Simões, Nelson Hamerschlak, Alicia Helena Magarinos Bozzano, Ernesto Mayta, Jorge Cortes, Raquel M. Bengió

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

Original language	English (US)
Pages (from-to)	451-458
Number of pages	8
Journal	Cancer Investigation
Volume	33
Issue number	9
DOIs	https://doi.org/10.3109/07357907.2015.1065499
State	Published - Oct 21 2015
Externally published	Yes

Keywords

BCR-ABL mutations
Chronic myeloid leukemia
Imatinib
Resistance
Tyrosine kinase inhibitors

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3109/07357907.2015.1065499

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Pagnano, K. B. B., Bendit, I., Boquimpani, C., De Souza, C. A., Miranda, E. C. M., Zalcberg, I., Larripa, I., Nardinelli, L., Silveira, R. A., Fogliatto, L., Spector, N., Funke, V., Pasquini, R., Hungria, V., Chiattone, C. S., Clementino, N., Conchon, M., Moiraghi, E. B., Lopez, J. L., ... Bengió, R. M. (2015). BCR-ABL Mutations in Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors and Impact on Survival. Cancer Investigation, 33(9), 451-458. https://doi.org/10.3109/07357907.2015.1065499

Pagnano, KBB, Bendit, I, Boquimpani, C, De Souza, CA, Miranda, ECM, Zalcberg, I, Larripa, I, Nardinelli, L, Silveira, RA, Fogliatto, L, Spector, N, Funke, V, Pasquini, R, Hungria, V, Chiattone, CS, Clementino, N, Conchon, M, Moiraghi, EB, Lopez, JL, Pavlovsky, C, Pavlovsky, MA, Cervera, EE, Meillon, LA, Simões, B, Hamerschlak, N, Bozzano, AHM, Mayta, E, Cortes, J & Bengió, RM 2015, 'BCR-ABL Mutations in Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors and Impact on Survival', Cancer Investigation, vol. 33, no. 9, pp. 451-458. https://doi.org/10.3109/07357907.2015.1065499

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title = "BCR-ABL Mutations in Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors and Impact on Survival",

abstract = "This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.",

keywords = "BCR-ABL mutations, Chronic myeloid leukemia, Imatinib, Resistance, Tyrosine kinase inhibitors",

author = "Pagnano, {Katia Borgia Barbosa} and Israel Bendit and Carla Boquimpani and {De Souza}, {Carmino Antonio} and Miranda, {Eliana C.M.} and Ilana Zalcberg and Irene Larripa and Luciana Nardinelli and Silveira, {Rosana Antunes} and Laura Fogliatto and Nelson Spector and Vaneuza Funke and Ricardo Pasquini and Vania Hungria and Chiattone, {Carlos S{\'e}rgio} and Nelma Clementino and Monika Conchon and Moiraghi, {Elena Beatriz} and Lopez, {Jose Luis} and Carolina Pavlovsky and Pavlovsky, {Miguel A.} and Cervera, {Eduardo E.} and Meillon, {Luis Antonio} and Belinda Sim{\~o}es and Nelson Hamerschlak and Bozzano, {Alicia Helena Magarinos} and Ernesto Mayta and Jorge Cortes and Bengi{\'o}, {Raquel M.}",

note = "Funding Information: KBP, VF, LF, MC,CB, BS,CP, EBMare membersofthe speakers{\textquoteright} Bureau of Bristol Myers Squibb (BMS) and Novartis. IZ received research grants from Novartis and BMS. JC received research support from Ariad, BMS, Novartis, Pfizer and Teva and is a consultant for Ariad, BMS, Pfizer and Teva. NS and RP: Novartis: Membership on an entity{\textquoteright}s Board of Directors or advisory committees. The other authors report no potential conflicts of interest. Funding Information: This study was supported in part by research funding from FAPESP (Fundac¸{\~a}o de Amparo {\`a} Pesquisa de Estado de S{\~a}o Paulo) (grants 03/12605-2R; 03/09054-4; and 05/59708-6) to KBP, from Fundac¸{\~a}o Maria Cec{\'i}lia de Souto Vidigal to IB, and from Novartis Argentina{\textquoteright} grants to RB. The authors would like to thank the data managers, physicians, and laboratory staff of the participant centers, in particular Luz Marina Majsa (from United States), Oscar Ballester (English review) and to doctors Riva ME; Lanari E; Milone J; Ventriglia V; Bullorsky E (for the contribution with their patients from Argentina); Anderson Tavares (Unicamp); Paola Cappelletti; and Simone Bonecker (INCA) (from Brazil). Publisher Copyright: {\textcopyright} 2015 Informa Healthcare USA, Inc.",

year = "2015",

month = oct,

day = "21",

doi = "10.3109/07357907.2015.1065499",

language = "English (US)",

volume = "33",

pages = "451--458",

journal = "Cancer Investigation",

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T1 - BCR-ABL Mutations in Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors and Impact on Survival

AU - Pagnano, Katia Borgia Barbosa

AU - Bendit, Israel

AU - Boquimpani, Carla

AU - De Souza, Carmino Antonio

AU - Miranda, Eliana C.M.

AU - Zalcberg, Ilana

AU - Larripa, Irene

AU - Nardinelli, Luciana

AU - Silveira, Rosana Antunes

AU - Fogliatto, Laura

AU - Spector, Nelson

AU - Funke, Vaneuza

AU - Pasquini, Ricardo

AU - Hungria, Vania

AU - Chiattone, Carlos Sérgio

AU - Clementino, Nelma

AU - Conchon, Monika

AU - Moiraghi, Elena Beatriz

AU - Lopez, Jose Luis

AU - Pavlovsky, Carolina

AU - Pavlovsky, Miguel A.

AU - Cervera, Eduardo E.

AU - Meillon, Luis Antonio

AU - Simões, Belinda

AU - Hamerschlak, Nelson

AU - Bozzano, Alicia Helena Magarinos

AU - Mayta, Ernesto

AU - Cortes, Jorge

AU - Bengió, Raquel M.

N1 - Funding Information: KBP, VF, LF, MC,CB, BS,CP, EBMare membersofthe speakers’ Bureau of Bristol Myers Squibb (BMS) and Novartis. IZ received research grants from Novartis and BMS. JC received research support from Ariad, BMS, Novartis, Pfizer and Teva and is a consultant for Ariad, BMS, Pfizer and Teva. NS and RP: Novartis: Membership on an entity’s Board of Directors or advisory committees. The other authors report no potential conflicts of interest. Funding Information: This study was supported in part by research funding from FAPESP (Fundac¸ão de Amparo à Pesquisa de Estado de São Paulo) (grants 03/12605-2R; 03/09054-4; and 05/59708-6) to KBP, from Fundac¸ão Maria Cecília de Souto Vidigal to IB, and from Novartis Argentina’ grants to RB. The authors would like to thank the data managers, physicians, and laboratory staff of the participant centers, in particular Luz Marina Majsa (from United States), Oscar Ballester (English review) and to doctors Riva ME; Lanari E; Milone J; Ventriglia V; Bullorsky E (for the contribution with their patients from Argentina); Anderson Tavares (Unicamp); Paola Cappelletti; and Simone Bonecker (INCA) (from Brazil). Publisher Copyright: © 2015 Informa Healthcare USA, Inc.

PY - 2015/10/21

Y1 - 2015/10/21

N2 - This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

AB - This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

KW - BCR-ABL mutations

KW - Chronic myeloid leukemia

KW - Imatinib

KW - Resistance

KW - Tyrosine kinase inhibitors

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VL - 33

SP - 451

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JO - Cancer Investigation

JF - Cancer Investigation

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ER -

BCR-ABL Mutations in Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors and Impact on Survival

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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