Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors

被引:55
作者
Falchi, Lorenzo [1 ]
Kantarjian, Hagop M. [1 ]
Wang, Xuemei [2 ]
Verma, Dushyant [1 ]
Quintas-Cardama, Alfonso [1 ]
O'Brien, Susan [1 ]
Jabbour, Elias J. [1 ]
Ravandi-Kashani, Farhad [1 ]
Borthakur, Gautam [1 ]
Garcia-Manero, Guillermo [1 ]
Verstovsek, Srdan [1 ]
Burger, Jan A. [1 ]
Luthra, Raja [3 ]
Cortes, Jorge E. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA
关键词
CHRONIC MYELOGENOUS LEUKEMIA; ALPHA PLUS CYTARABINE; IMATINIB MESYLATE; INTERFERON-ALPHA; THERAPY; CML; DISCONTINUATION; DASATINIB; REMISSION; NILOTINIB;
D O I
10.1002/ajh.23560
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Most patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKI) achieve complete cytogenetic response (CCyR). An increasing number of patients also achieve deep molecular responses (MR). We determined the frequency and significance of deep MR after TKI therapy for CML in CP. MR included: major molecular response (MMR), MR4, MR4.5, and undetectable transcripts (UND), i.e., BCR-ABL/ABL of <= 0.1, <= 0.01, <= 0.0032%, and undetectable transcripts, respectively. Four hundred eighty-three patients received imatinib 400 mg/day (IM400, 71, July 2000 to April 2001), imatinib 800 mg/day (IM800, 204, June 2001 to July 2005), nilotinib (106, July 2005 to date), or dasatinib (102, November 2005 to date). UND rates at 36 months were 18.1, 30.6, 29.2, and 28.6%, respectively. Patients achieving UND have superior transformation-free survival (TFS) and overall survival (OS) versus those obtaining <= MMR, but not other MR levels. At the 18- and 24-month landmark analysis, patients achieving UND have no advantage in TFS and OS compared to those achieving a lesser degree of MR. Among patients achieving MR4.5, those who maintain it for >= 2 years (susMR4.5) have no additional benefit in TFS or OS. Most patients with early CP CML receiving TKI achieve MMR. BCR-ABL transcripts become undetectable in a significant fraction of them. Deeper MR at 18 or 24 months are not associated with a benefit in TFS or OS. Furthermore, achieving susMR4.5 does not appear to further reduce the risk of transformation or death. Am. J. Hematol. 88: 1024-1029, 2013. (C) 2013 Wiley Periodicals, Inc.
引用
收藏
页码:1024 / 1029
页数:6
相关论文
共 29 条
[1]   Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia [J].
Branford, S. ;
Cross, N. C. P. ;
Hochhaus, A. ;
Radich, J. ;
Saglio, G. ;
Kaeda, J. ;
Goldman, J. ;
Hughes, T. .
LEUKEMIA, 2006, 20 (11) :1925-1930
[2]   Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase [J].
Branford, S ;
Rudzki, Z ;
Harper, A ;
Grigg, A ;
Taylor, K ;
Durrant, S ;
Arthur, C ;
Browett, P ;
Schwarer, AP ;
Ma, D ;
Seymour, JF ;
Bradstock, K ;
Joske, D ;
Lynch, K ;
Gathmann, I ;
Hughes, TP .
LEUKEMIA, 2003, 17 (12) :2401-2409
[3]   Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML [J].
Branford, Susan ;
Yeung, David T. ;
Ross, David M. ;
Prime, Jodi A. ;
Field, Chani R. ;
Altamura, Haley K. ;
Yeoman, Alexandra L. ;
Georgievski, Jasmina ;
Jamison, Bronte A. ;
Phillis, Stuart ;
Sullivan, Brad ;
Briggs, Nancy E. ;
Hertzberg, Mark ;
Seymour, John F. ;
Reynolds, John ;
Hughes, Timothy P. .
BLOOD, 2013, 121 (19) :3818-3824
[4]   Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate [J].
Cortes, J ;
Talpaz, M ;
O'Brien, S ;
Jones, D ;
Luthra, R ;
Shan, J ;
Giles, F ;
Faderl, S ;
Verstovsek, S ;
Garcia-Manero, G ;
Rios, MB ;
Kantarjian, H .
CLINICAL CANCER RESEARCH, 2005, 11 (09) :3425-3432
[5]   Front-Line and Salvage Therapies With Tyrosine Kinase Inhibitors and Other Treatments in Chronic Myeloid Leukemia [J].
Cortes, Jorge ;
Hochhaus, Andreas ;
Hughes, Timothy ;
Kantarjian, Hagop .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (05) :524-531
[6]   Phase III, Randomized, Open-Label Study of Daily Imatinib Mesylate 400 mg Versus 800 mg in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecular End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study [J].
Cortes, Jorge E. ;
Baccarani, Michele ;
Guilhot, Francois ;
Druker, Brian J. ;
Branford, Susan ;
Kim, Dong-Wook ;
Pane, Fabrizio ;
Pasquini, Ricardo ;
Goldberg, Stuart L. ;
Kalaycio, Matt ;
Moiraghi, Beatriz ;
Rowe, Jacob M. ;
Tothova, Elena ;
De Souza, Carmino ;
Rudoltz, Marc ;
Yu, Richard ;
Krahnke, Tillmann ;
Kantarjian, Hagop M. ;
Radich, Jerald P. ;
Hughes, Timothy P. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (03) :424-430
[7]   Nilotinib As Front-Line Treatment for Patients With Chronic Myeloid Leukemia in Early Chronic Phase [J].
Cortes, Jorge E. ;
Jones, Dan ;
O'Brien, Susan ;
Jabbour, Elias ;
Konopleva, Marina ;
Ferrajoli, Alessandra ;
Kadia, Tapan ;
Borthakur, Gautam ;
Stigliano, Denise ;
Shan, Jianqin ;
Kantarjian, Hagop .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (03) :392-397
[8]   Results of Dasatinib Therapy in Patients With Early Chronic-Phase Chronic Myeloid Leukemia [J].
Cortes, Jorge E. ;
Jones, Dan ;
O'Brien, Susan ;
Jabbour, Elias ;
Ravandi, Farhad ;
Koller, Charles ;
Borthakur, Gautam ;
Walker, Brenda ;
Zhao, Weiqiang ;
Shan, Jianqin ;
Kantarjian, Hagop .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (03) :398-404
[9]   High-Dose Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: High Rates of Rapid Cytogenetic and Molecular Responses [J].
Cortes, Jorge E. ;
Kantarjian, Hagop M. ;
Goldberg, Stuart L. ;
Powell, Bayard L. ;
Giles, Francis J. ;
Wetzler, Meir ;
Akard, Luke ;
Burke, John M. ;
Kerr, Robert ;
Saleh, Mansoor ;
Salvado, August ;
McDougall, Karen ;
Albitar, Maher ;
Radich, Jerald .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (28) :4754-4759
[10]   Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia [J].
Druker, Brian J. ;
Guilhot, Francois ;
O'Brien, Stephen G. ;
Gathmann, Insa ;
Kantarjian, Hagop ;
Gattermann, Norbert ;
Deininger, Michael W. N. ;
Silver, Richard T. ;
Goldman, John M. ;
Stone, Richard M. ;
Cervantes, Francisco ;
Hochhaus, Andreas ;
Powell, Bayard L. ;
Gabrilove, Janice L. ;
Rousselot, Philippe ;
Reiffers, Josy ;
Cornelissen, Jan J. ;
Hughes, Timothy ;
Agis, Hermine ;
Fischer, Thomas ;
Verhoef, Gregor ;
Shepherd, John ;
Saglio, Giuseppe ;
Gratwohl, Alois ;
Nielsen, Johan L. ;
Radich, Jerald P. ;
Simonsson, Bengt ;
Taylor, Kerry ;
Baccarani, Michele ;
So, Charlene ;
Letvak, Laurie ;
Larson, Richard A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (23) :2408-2417