An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors

被引:4
作者
Garcia-Gutierrez, Valentin [1 ]
Carlos Hernandez-Boluda, Juan [2 ]
机构
[1] Univ Alcala, Hosp Univ Ramon y Cajal, Serv Hematol, IRYCIS, Madrid, Spain
[2] Univ Valencia, Hosp Clin Univ, Serv Hematol, INCLIVA, Valencia, Spain
关键词
Allosteric inhibition; asciminib; chronic myeloid leukemia; intolerance; resistance; STAMP inhibitor; tyrosine kinase inhibitors; ADVERSE EVENTS; PONATINIB; IMATINIB; BOSUTINIB; EFFICACY; TRIAL;
D O I
10.1080/17474086.2022.2080049
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: To date, five tyrosine kinase inhibitors (TKIs) are available for treating chronic myeloid leukemia (CML) patients in clinical practice. Despite this, a significant proportion of patients will ultimately develop failure to approved TKIs due to intolerance or resistance. Consequently, new treatment approaches are still required in this unmet clinical need. Asciminib, a first-in-class BCR:: ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to prior TKI treatment. Areas covered: This review will cover the mechanism of action, pharmacokinetic profile, and clinical data of asciminib based on available information from laboratory studies, clinical trials, and real-world evidence. Expert opinion: Recent approval of asciminib will require positioning of this drug in the treatment algorithm of CML patients failing initial TKI therapy. Available data support the lack of cross-intolerance of asciminib with other TKIs and its favorable cardiovascular toxicity profile. In addition, asciminib has demonstrated considerable efficacy in CML patients who have failed at least two TKIs, although preliminary data suggest that this efficacy may be lower in those previously exposed to ponatinib. The introduction of asciminib in clinical practice may represent an important step forward in the management of CML.
引用
收藏
页码:477 / 484
页数:8
相关论文
共 40 条
[1]  
Andorsky D., 2021, BLOOD, V138, P3599
[2]  
[Anonymous], ASCIMINIB TREATMENT
[3]   Chronic myeloid leukaemia [J].
Apperley, Jane F. .
LANCET, 2015, 385 (9976) :1447-1459
[4]   Asciminib: an investigational agent for the treatment of chronic myeloid leukemia [J].
Breccia, Massimo ;
Colafigli, Gioia ;
Scalzulli, Emilia ;
Martelli, Maurizio .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2021, 30 (08) :803-811
[5]  
Ciftciler R, 2021, EUR REV MED PHARMACO, V25, P7787, DOI 10.26355/eurrev_202112_27625
[6]   A Phase 2 Trial of Ponatinib in Philadelphia Chromosome-Positive Leukemias [J].
Cortes, J. E. ;
Kim, D. -W. ;
Pinilla-Ibarz, J. ;
le Coutre, P. ;
Paquette, R. ;
Chuah, C. ;
Nicolini, F. E. ;
Apperley, J. F. ;
Khoury, H. J. ;
Talpaz, M. ;
DiPersio, J. ;
DeAngelo, D. J. ;
Abruzzese, E. ;
Rea, D. ;
Baccarani, M. ;
Mueller, M. C. ;
Gambacorti-Passerini, C. ;
Wong, S. ;
Lustgarten, S. ;
Rivera, V. M. ;
Clackson, T. ;
Turner, C. D. ;
Haluska, F. G. ;
Guilhot, F. ;
Deininger, M. W. ;
Hochhaus, A. ;
Hughes, T. ;
Goldman, J. M. ;
Shah, N. P. ;
Kantarjian, H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (19) :1783-1796
[7]  
Cortes JE., 2018, HEMASPHERE, V2, P1
[8]   Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial [J].
Cortes, Jorge ;
Apperley, Jane ;
Lomaia, Elza ;
Moiraghi, Beatriz ;
Sutton, Maria Undurraga ;
Pavlovsky, Carolina ;
Chuah, Charles ;
Sacha, Tomasz ;
Lipton, Jeffrey H. ;
Schiffer, Charles A. ;
McCloskey, James ;
Hochhaus, Andreas ;
Rousselot, Philippe ;
Rosti, Gianantonio ;
de Lavallade, Hugues ;
Turkina, Anna ;
Rojas, Christine ;
Arthur, Christopher Kevin ;
Maness, Lori ;
Talpaz, Moshe ;
Mauro, Michael ;
Hall, Tracey ;
Lu, Vickie ;
Srivastava, Shouryadeep ;
Deininger, Michael .
BLOOD, 2021, 138 (21) :2042-2050
[9]   Third-line therapy for chronic myeloid leukemia: current status and future directions [J].
Cortes, Jorge ;
Lang, Fabian .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2021, 14 (01)
[10]   Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial [J].
Cortes, Jorge E. ;
Kim, Dong-Wook ;
Pinilla-Ibarz, Javier ;
le Coutre, Philipp D. ;
Paquette, Ronald ;
Chuah, Charles ;
Nicolini, Franck E. ;
Apperley, Jane F. ;
Khoury, H. Jean ;
Talpaz, Moshe ;
DeAngelo, Daniel J. ;
Abruzzese, Elisabetta ;
Rea, Delphine ;
Baccarani, Michele ;
Mueller, Martin C. ;
Gambacorti-Passerini, Carlo ;
Lustgarten, Stephanie ;
Rivera, Victor M. ;
Haluska, Frank G. ;
Guilhot, Francois ;
Deininger, Michael W. ;
Hochhaus, Andreas ;
Hughes, Timothy P. ;
Shah, Neil P. ;
Kantarjian, Hagop M. .
BLOOD, 2018, 132 (04) :393-404