Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia

被引:489
作者
Picard, Stephane
Titier, Karine
Etienne, Gabriel
Teilhet, Ernmanuelle
Ducint, Dominique
Bernard, Marie-Agnes
Lassalle, Regis
Marit, Gerald
Reiffers, Josy
Begaud, Bernard
Moore, Nicholas
Molimard, Mathieu
Mahon, Francois-Xavier
机构
[1] Univ Victor Segalen Bordeaux 2, Lab Hematopoiese Normale & Pathol, INSERM E217, F-33076 Bordeaux, France
[2] CHU Bordeaux, Dept Clin Pharmacol & Toxicol, Bordeaux, France
[3] INSERM U657, Bordeaux, France
[4] Reg Canc Ctr, Dept Hematol, Inst Bergonie, Bordeaux, France
[5] CHU Bordeaux, Dept Hematol & Blood Dis, Bordeaux, France
关键词
D O I
10.1182/blood-2006-07-036012
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Using high-performance liquid chrometography-tandem mass spectrometry, we assessed trough imatinib plasma levels in 68 patients with chronic myeloid leukemia (CML) who responded or not to standard-close imatinib, after at least 12 months' treatment. Mean trough imatinib plasma levels were significantly higher in the group with complete cytogenetic response (56 patients) than in the group without (12 patients; P = .03) and higher in the group with major molecular response (MMR) than in the group without (34 patients [1452 +/- 649 ng/mL] versus 34 patients [869 +/- 427 ng/mL]; P < .001). Regarding trough imatinib plasma levels and their discrimination potential for MMR, the area under receiver operating characteristic curve was 0.775, with best sensitivity (77%) and specificity (71%) at a plasma threshold of 1002 ng/mL. Therefore, monitoring of imatinib plasma levels could be very useful for the management of patients with CML or should at least be checked in the case of treatment failure or suboptimal response.
引用
收藏
页码:3496 / 3499
页数:4
相关论文
共 20 条
[1]  
Buchdunger E, 1996, CANCER RES, V56, P100
[2]  
Colombat M, 2006, HAEMATOL-HEMATOL J, V91, P162
[3]   BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571 [J].
Donato, NJ ;
Wu, JY ;
Stapley, J ;
Gallick, G ;
Lin, H ;
Arlinghaus, R ;
Talpaz, M .
BLOOD, 2003, 101 (02) :690-698
[4]   Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells [J].
Druker, BJ ;
Tamura, S ;
Buchdunger, E ;
Ohno, S ;
Segal, GM ;
Fanning, S ;
Zimmermann, J ;
Lydon, NB .
NATURE MEDICINE, 1996, 2 (05) :561-566
[5]   Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. [J].
Druker, BJ ;
Talpaz, M ;
Resta, DJ ;
Peng, B ;
Buchdunger, E ;
Ford, JM ;
Lydon, NB ;
Kantarjian, H ;
Capdeville, R ;
Ohno-Jones, S ;
Sawyers, CL .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) :1031-1037
[6]   Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification [J].
Gorre, ME ;
Mohammed, M ;
Ellwood, K ;
Hsu, N ;
Paquette, R ;
Rao, PN ;
Sawyers, CL .
SCIENCE, 2001, 293 (5531) :876-880
[7]   Monitoring CML patients responding to treatment with tyrosine kinase inhibitors:: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results [J].
Hughes, Timothy ;
Deininger, Michael ;
Hochhaus, Andreas ;
Branford, Susan ;
Radich, Jerald ;
Kaecla, Jaspal ;
Baccarani, Michele ;
Cortes, Jorge ;
Cross, Nicholas C. P. ;
Druker, Brian J. ;
Gabert, Jean ;
Grimwade, David ;
Hehlmann, Ruediger ;
Kamel-Reid, Suzanne ;
Lipton, Jeffrey H. ;
Longtine, Janina ;
Martinelli, Giovanni ;
Saglio, Giuseppe ;
Soverini, Simona ;
Stock, Wendy ;
Goldman, John M. .
BLOOD, 2006, 108 (01) :28-37
[8]   Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia [J].
Hughes, TP ;
Kaeda, J ;
Branford, S ;
Rudzki, Z ;
Hochhaus, A ;
Hensley, ML ;
Gathmann, I ;
Bolton, AE ;
van Hoomissen, IC ;
Goldman, JM ;
Radich, JP ;
Taylor, K ;
Durrant, S ;
Schwarer, A ;
Joske, D ;
Seymour, J ;
Grigg, A ;
Ma, D ;
Arthur, C ;
Bradstock, K ;
Joshua, D ;
Lechner, K ;
Verhoef, G ;
Louwagie, A ;
Martiat, P ;
Straetmans, N ;
Bosly, A ;
Shepherd, J ;
Shustik, C ;
Lipton, J ;
Kovacs, DM ;
Turner, AR ;
Nielsen, JL ;
Birgens, H ;
Bjerrum, OW ;
Guilhot, F ;
Reiffers, J ;
Rousselot, P ;
Facon, T ;
Harousseau, JL ;
Tulliez, M ;
Guerci, A ;
Blaise, D ;
Maloisel, F ;
Michallet, M ;
Fischer, T ;
Hossfeld, D ;
Mertelsmann, R ;
Andreesen, R ;
Nerl, C .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (15) :1423-1432
[9]   High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia [J].
Kantarjian, H ;
Talpaz, M ;
O'Brien, SS ;
Garcia-Manero, G ;
Verstovsek, S ;
Giles, F ;
Rios, MB ;
Shan, JQ ;
Letvak, L ;
Thomas, D ;
Faderl, S ;
Ferrajoli, A ;
Cortes, J .
BLOOD, 2004, 103 (08) :2873-2878
[10]   Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL [J].
Kantarjian, Hagop ;
Giles, Francis ;
Wunderle, Lydia ;
Bhalla, Kapil ;
O'Brien, Susan ;
Wassmann, Barbara ;
Tanaka, Chiaki ;
Manley, Paul ;
Rae, Patricia ;
Mietlowski, William ;
Bochinski, Kathy ;
Hochhaus, Andreas ;
Griffin, James D. ;
Hoelzer, Dieter ;
Albitar, Maher ;
Dugan, Margaret ;
Cortes, Jorge ;
Alland, Leila ;
Ottmann, Oliver G. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (24) :2542-2551