Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response

被引:28
作者
Cervantes, Francisco [1 ]
Correa, Juan-Gonzalo [1 ]
Perez, Isabel [2 ]
Garcia-Gutierrez, Valentin [3 ]
Redondo, Sara [2 ]
Colomer, Dolors [4 ]
Jimenez-Velasco, Antonio [5 ]
Steegmann, Juan-Luis [6 ]
Sanchez-Guijo, Fermin [7 ]
Ferrer-Marin, Francisca [8 ]
Pereira, Arturo [1 ]
Osorio, Santiago
机构
[1] Univ Barcelona, Dept Hematol, Hosp Clin, IDIBAPS, Villarroel 170, E-08036 Barcelona, Spain
[2] Hosp Gregorio Maranon, Madrid, Spain
[3] Hosp Ramon & Cajal, Madrid, Spain
[4] Hosp Clin Barcelona, IDIBAPS, Hematopathol Unit, Barcelona, Spain
[5] Hosp Reg Univ Malaga, IBIMA, Malaga, Spain
[6] Hosp Princesa, Madrid, Spain
[7] IBSAL Hosp Clin Univ, Salamanca, Spain
[8] UCAM, Hosp Univ Morales Meseguer, IMIB, Murcia, Spain
关键词
Chronic myeloid leukemia; Imatinib; Toxicity; Dose reduction; Deep molecular response; QUALITY-OF-LIFE; CHRONIC MYELOGENOUS LEUKEMIA; PATIENTS RECEIVING IMATINIB; CHRONIC-PHASE; FOLLOW-UP; DISEASE; DISCONTINUATION; INTOLERANCE; RESISTANCE; DASATINIB;
D O I
10.1007/s00277-016-2839-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To determine whether a lower imatinib dose could minimize toxicity while maintaining the molecular response (MR), imatinib dose was reduced to 300 mg daily in 43 patients with chronic myeloid leukemia (CML) in sustained deep molecular response to first-line imatinib 400 mg daily. At the time of dose reduction, median duration of the deep response was 4.1 (interquartile range (IQR) 2.2-5.9) years; molecular response was MR4, MR4.5, and MR5 of the international scale in 6, 28, and 9 patients, respectively. Toxicity grade was 1, 2, and 3 in 28, 8, and 1 patients, respectively; 6 patients underwent dose reduction without having side effects. With a median of 1.6 (IQR 0.7-3.2) years on imatinib 300 mg daily, only one patient lost the deep molecular response to MR3. At the last follow-up, response was MR3, MR4, MR4.5, and MR5 in 1, 3, 9, and 30 patients, respectively. Toxicity improvement was observed in 23 (62.2 %) of the 37 patients with side effects, decreasing to grade 0 in 20 of them. All but one anemic patients improved (p = 0.01), the median Hb increase in this subgroup of patients being 1 g/dL. In CML patients with sustained deep response to the standard imatinib dose, reducing to 300 mg daily significantly improves tolerability and preserves efficacy.
引用
收藏
页码:81 / 85
页数:5
相关论文
共 21 条
[1]   Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group [J].
Cervantes, Francisco ;
Lopez-Garrido, Pilar ;
Montero, Maria-Isabel ;
Jonte, Fermin ;
Martinez, Jesus ;
Hernandez-Boluda, Juan-Carlos ;
Calbacho, Maria ;
Sureda, Anna ;
Perez-Rus, Gloria ;
Nieto, Jose B. ;
Perez-Lopez, Cristina ;
Roman-Gomez, Jose ;
Gonzalez, Marcos ;
Pereira, Arturo ;
Colomer, Dolors .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (08) :1317-1324
[2]  
Cortes J, 2009, BLOOD, V114, P267
[3]   Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia [J].
Cross, N. C. P. ;
White, H. E. ;
Colomer, D. ;
Ehrencrona, H. ;
Foroni, L. ;
Gottardi, E. ;
Lange, T. ;
Lion, T. ;
Polakova, K. Machova ;
Dulucq, S. ;
Martinelli, G. ;
Leibundgut, E. Oppliger ;
Pallisgaard, N. ;
Barbany, G. ;
Sacha, T. ;
Talmaci, R. ;
Izzo, B. ;
Saglio, G. ;
Pane, F. ;
Mueller, M. C. ;
Hochhaus, A. .
LEUKEMIA, 2015, 29 (05) :999-1003
[4]   Imatinib for newly diagnosed patients with chronic myeloid leukemia: Incidence of sustained responses in an intention-to-treat analysis [J].
de Lavallade, Hugues ;
Apperley, Jane F. ;
Khorashad, Jamshid S. ;
Milojkovic, Dragana ;
Reid, Alistair G. ;
Bua, Marco ;
Szydlo, Richard ;
Olavarria, Eduardo ;
Kaeda, Jaspal ;
Goldman, John M. ;
Marin, David .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (20) :3358-3363
[5]   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
[6]   Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib [J].
Efficace, F. ;
Baccarani, M. ;
Breccia, M. ;
Cottone, F. ;
Alimena, G. ;
Deliliers, G. L. ;
Barate, C. ;
Specchia, G. ;
Di Lorenzo, R. ;
Luciano, L. ;
Turri, D. ;
Martino, B. ;
Stagno, F. ;
Dabusti, M. ;
Bergamaschi, M. ;
Leoni, P. ;
Simula, M. P. ;
Levato, L. ;
Fava, C. ;
Veneri, D. ;
Sica, S. ;
Rambaldi, A. ;
Rosti, G. ;
Vignetti, M. ;
Mandelli, F. .
LEUKEMIA, 2013, 27 (07) :1511-1519
[7]   A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment [J].
Faber, Edgar ;
Divoka, Martina ;
Skoumalova, Ivana ;
Novak, Martin ;
Maresova, Ivana ;
Micova, Katerina ;
Friedecky, David ;
Adam, Tomas ;
Jarosova, Marie ;
Indrak, Karel .
LEUKEMIA & LYMPHOMA, 2016, 57 (02) :370-375
[8]   Quality of Life and Long-Term Therapy in Patients with Chronic Myeloid Leukemia [J].
Flynn, Kathryn E. ;
Atallah, Ehab .
CURRENT HEMATOLOGIC MALIGNANCY REPORTS, 2016, 11 (02) :80-85
[9]   Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up [J].
Gambacorti-Passerini, Carlo ;
Bruemmendorf, Tim H. ;
Kim, Dong-Wook ;
Turkina, Anna G. ;
Masszi, Tamas ;
Assouline, Sarit ;
Durrant, Simon ;
Kantarjian, Hagop M. ;
Khoury, H. Jean ;
Zaritskey, Andrey ;
Shen, Zhi-Xiang ;
Jin, Jie ;
Vellenga, Edo ;
Pasquini, Ricardo ;
Mathews, Vikram ;
Cervantes, Francisco ;
Besson, Nadine ;
Turnbull, Kathleen ;
Leip, Eric ;
Kelly, Virginia ;
Cortes, Jorge E. .
AMERICAN JOURNAL OF HEMATOLOGY, 2014, 89 (07) :732-742
[10]   Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase [J].
Guerin, Annie ;
Chen, Lei ;
Ionescu-Ittu, Raluca ;
Marynchenko, Maryna ;
Nitulescu, Roy ;
Hiscock, Robert ;
Keir, Christopher ;
Wu, Eric Qiong .
CURRENT MEDICAL RESEARCH AND OPINION, 2014, 30 (11) :2317-2328