Practical management of patients with chronic myeloid leukemia who develop tyrosine kinase inhibitor-resistant BCR-ABL1 mutations

Therapeutic Advances in Hematology

Volumn 5, Issue 4, 2014, Pages 107-120

  Ai, Jing ^a   Tiu, Ramon V ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

BCR ABL1; chronic myeloid leukemia; DNA mutational analysis; drug resistance; missense mutation

Indexed keywords

EID: 84993705074     PISSN: 20406207     EISSN: 20406215     Source Type: Journal    
DOI: 10.1177/2040620714537865     Document Type: Review

References (67)

1. Alikian M. Gerrard G. Subramanian P. Mudge K. Foskett P. Khorashad J. et al. (2012) Bcr-Abl1 kinase domain mutations: methodology and clinical evaluation. Am J Hematol 87: 298–304.
2. American Cancer Society (2013) Cancer Facts and Figures 2013. Available at: http://www.cancer.org/research/cancerfactsfigures/cancerfactsfigures/cancer-facts-figures-2013 (accessed 19 November 2013).
3. Baccarani M. Saglio G. Goldman J. Hochhaus A. Simonsson B. Appelbaum F. et al. (2006) Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European Leukemianet. Blood 108: 1809–1820.
4. Bixby D. Talpaz M. (2009) Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematology Am Soc Hematol Educ Progra 461–476.
5. Bjorkholm M. Ohm L. Eloranta S. Derolf A. Hultcrantz M. Sjoberg J. et al. (2011) Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008. J Clin Oncol 29: 2514–2520.
6. Branford S. Rudzki Z. Walsh S. Parkinson I. Grigg A. Szer J. et al. (2003) Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 102: 276–283.
7. Brouckova A. Soverini S. de Benedittis C. Klamova H. Salek C. Trneny M. et al. (2012) Ultradeep-amplicon pyrosequencing for mutation detection in the kinase domain of BCR-ABL revealed artificial low-level variants that need to be avoided for relevant mutational data interpretation. Blood (ASH Annual Meeting Abstracts) 120: 1396.
8. Brummendorf T. Kantarjian H. Gambacorti-Passerini C. Guilhot F. Akard L. Doshi V. et al. (2012) Assessment of early molecular response as a predictor of long-term clinical outcomes in the phase 3 BELA Study. Blood (ASH Annual Meeting Abstracts) 120: 69.
9. Brunner A. Campigotto F. Sadrzadeh H. Drapkin B. Chen Y. Neuberg D. et al. (2013) Trends in all-cause mortality among patients with chronic myeloid leukemia: a Surveillance, Epidemiology, and End Results database analysis Cancer 119: 2620–2629.
10. Choy B. Mcclarty G. Chan A. Thelander L. Wright J. (1988) Molecular mechanisms of drug resistance involving ribonucleotide reductase: hydroxyurea resistance in a series of clonally related mouse cell lines selected in the presence of increasing drug concentrations. Cancer Res 48: 2029–2035.
11. Cortes J. Jones D. O'Brien S. Jabbour E. Konopleva M. Ferrajoli A. et al. (2010) Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol 28: 392–397.
12. Cortes J. Kantarjian H. Shah N. Bixby D. Mauro M. Flinn I. et al. (2012 a) Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med 367: 2075–2088.
13. Cortes J. Kim D. Pinilla-Ibarz J. Le Coutre P. Paquette R. Chuah C. et al. (2012 b) A pivotal phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+All) resistant or intolerant to dasatinib or nilotinib, or with the T315i BCR-ABL mutation: 12-month follow-up of the PACE trial. Blood (ASH Annual Meeting Abstracts) 120: 163.
14. Cortes J. Lipton J. Rea D. Digumarti R. Chuah C. Nanda N. et al. (2012 c) Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315i mutation. Blood 120: 2573–2580.
15. Deininger M. Buchdunger E. Druker B. (2005) The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 105: 2640–2653.
16. Deininger M. O'Brien S. Guilhot F. Goldman J. Hochhaus A. Hughes T. et al. (2009) International Randomized Study of Interferon Vs STI 571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood (ASH Annual Meeting Abstracts) 114: 1126.
17. Deininger M. Mcgreevey L. Willis S. Bainbridge T. Druker B. Heinrich M. (2004) Detection of ABL kinase domain mutations with denaturing high-performance liquid chromatography. Leukemia 18: 864–871.
18. Druker B. Guilhot F. O'Brien S. Goldman J. Hochhaus A. Hughes T. et al. (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355: 2408–2417.
19. Ernst T. Gruber F. Pelz-Ackermann O. Maier J. Pfirrmann M. Muller M. et al. (2009) A co-operative evaluation of different methods of detecting BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on second-line dasatinib or nilotinib therapy after failure of imatinib. Haematologica 94: 1227–1235.
20. Faderl S. Talpaz M. Estrov Z. Kantarjian H. (1999) Chronic myelogenous leukemia: biology and therapy. Ann Intern Med 131: 207–219.
21. Golas J. Arndt K. Etienne C. Lucas J. Nardin D. Gibbons J. et al. (2003) SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K 562 xenografts in nude mice. Cancer Res 63: 375–381.
22. Gorre M. Mohammed M. Ellwood K. Hsu N. Paquette R. Rao P. et al. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293: 876–880.
23. Hait W. Choudhury S. Srimatkandada S. Murren J. (1993) Sensitivity of K 562 human chronic myelogenous leukemia blast cells transfected with a human multidrug resistance cDNA to cytotoxic drugs and differentiating agents. J Clin Invest 91: 2207–2215.
24. Hanfstein B. Muller M. Hehlmann R. Erben P. Lauseker M. Fabarius A. et al. (2012) Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 26: 2096–2102.
25. Hochhaus A. Hughes T. Saglio G. Guilhot F. Al-Ali H. Rosti G. et al. (2012) Outcome of patients with chronic myeloid leukemia in chronic phase (CML-CP) based on early molecular response and factors associated with early response: 4-year follow-up data from ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Patients). Blood (ASH Annual Meeting Abstracts) 120: 167.
26. Hochhaus A. Saglio G. Larson R. Kim D. Etienne G. Rosti G. et al. (2013) Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood 121: 3703–3708.
27. Huang W. Metcalf C. Sundaramoorthi R. Wang Y. Zou D. Thomas R. et al. (2010) Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)-methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J Med Chem 53: 4701-4711.
28. Hughes T. Deininger M. Hochhaus A. Branford S. Radich J. Kaeda J. et al. (2006) 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. Blood 108: 28–37.
29. Jabbour E. Kantarjian H. Jones D. Talpaz M. Bekele N. O'Brien S. et al. (2006) Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia 20: 1767–1773.
30. Kantarjian H. Larson R. Cortes J. Deering K. Mauro M. (2013) Current practices in the management of chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk 13: 48–54.
31. Kantarjian H. O'Brien S. Jabbour E. Garcia-Manero G. Quintas-Cardama A. Shan J. et al. (2012 a) Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood 119: 1981–1987.
32. Kantarjian H. Shah N. Cortes J. Baccarani M. Agarwal M. Undurraga M. et al. (2012 b) Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 119: 1123–1129.
33. Kantarjian H. Shah N. Hochhaus A. Cortes J. Shah S. Ayala M. et al. (2010) Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 362: 2260–2270.
34. Lahaye T. Riehm B. Berger U. Paschka P. Muller M. Kreil S. et al. (2005) Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer 103: 1659–1669.
35. Landolfo S. Guarini A. Riera L. Gariglio M. Gribaudo G. Cignetti A. et al. (2000) Chronic myeloid leukemia cells resistant to interferon-alpha lack STAT 1 expression. Hematol J 1: 7–14.
36. Laneuville P. Dilea C. Yin O. Woodman R. Mestan J. Manley P. (2010) Comparative in vitro cellular data alone are insufficient to predict clinical responses and guide the choice of BCR-ABL inhibitor for treating imatinib-resistant chronic myeloid leukemia. J Clin Oncol 28: e169–e171; author reply e172.
37. Lange T. Ernst T. Gruber F. Maier J. Cross M. Muller M. et al. (2013) The quantitative level of T315I mutated BCR-ABL predicts for major molecular response to second-line nilotinib or dasatinib treatment in patients with chronic myeloid leukemia. Haematologica 98: 714–717.
38. Larson R. Hochhaus A. Hughes T. Clark R. Etienne G. Kim D. et al. (2012) Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 26: 2197–2203.
39. Levinson N. Boxer S. (2012) Structural and Spectroscopic analysis of the kinase inhibitor bosutinib and an isomer of bosutinib binding to the ABL tyrosine kinase domain. PloS ONE 7: e29828.
40. Lombardo L. Lee F. Chen P. Norris D. Barrish J. Behnia K. et al. (2004) Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src / Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 47: 6658–6661.
41. Manley P. Stiefl N. Cowan-Jacob S. Kaufman S. Mestan J. Wartmann M. et al. (2010) Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib. Bioorg Med Chem 18: 6977–6986.
42. Marin D. Ibrahim A. Lucas C. Gerrard G. Wang L. Szydlo R. et al. (2012) Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol 30: 232–238.
43. National Comprehensive Cancer Network (NCCN) (2014) Clinical Practice Guidelines in Oncology. Chronic Myelogenous Leukemia. Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf (accessed 19 November 2013).
44. O'Brien S. Guilhot F. Larson R. Gathmann I. Baccarani M. Cervantes F. et al. (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348: 994–1004.
45. O'Hare T. Eide C. Deininger M. (2007) Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 110: 2242–2249.
46. O'Hare T. Walters D. Stoffregen E. Jia T. Manley P. Mestan J. et al. (2005) In vitro activity of Bcr-Abl inhibitors AMN 107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 65: 4500–4505.
47. Quintas-Cardama A. Cortes J. (2009) Molecular biology of BCR-ABL1-positive chronic myeloid leukemia. Blood 113: 1619–1630.
48. Quintas-Cardama A. Kantarjian H. Cortes J. (2009) Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control 16: 122–131.
49. Radich J. Kopecky K. Appelbaum F. Kamel-Reid S. Stock W. Malnassy G. et al. (2012) A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia. Blood 120: 3898–3905.
50. Razga F. Jurcek T. Zackova D. Dvorakova D. Toskova M. Jeziskova I. et al. (2012) Role of treatment in the appearance and selection of BCR-ABL1 kinase domain mutations. Mol Diagn Ther 16: 251–259.
51. Redaelli S. Piazza R. Rostagno R. Magistroni V. Perini P. Marega M. et al. (2009) Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR / ABL mutants. J Clin Oncol 27: 469–471.
52. Reddy E. Aggarwal A. (2012) The ins and outs of Bcr-Abl inhibition. Genes Cancer 3: 447–454.
53. Roche-Lestienne C. Soenen-Cornu V. Grardel-Duflos N. Lai J. Philippe N. Facon T. et al. (2002) Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood 100: 1014–1018.
54. Saglio G. Kantarjian H. Shah N. Jabbour E. Quintas-Cardama A. Steegmann J. et al. (2012) Early response (molecular and cytogenetic) and long-term outcomes in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): exploratory analysis of DASISION 3-year data. Blood (ASH Annual Meeting Abstracts) 120: 1675.
55. Saglio G. Kim D. Issaragrisil S. Le Coutre P. Etienne G. Lobo C. et al. (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362: 2251–2259.
56. Schindler T. Bornmann W. Pellicena P. Miller W. Clarkson B. Kuriyan J. (2000) Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 289: 1938–1942.
57. Shah N. Nicoll J. Nagar B. Gorre M. Paquette R. Kuriyan J. et al. (2002) Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2: 117–125.
58. Shah N. Skaggs B. Branford S. Hughes T. Nicoll J. Paquette R. et al. (2007) Sequential ABL kinase inhibitor therapy selects for compound drug-resistant bcr-abl mutations with altered oncogenic potency. J Clin Invest 117: 2562–2569.
59. Soverini S. Colarossi S. Gnani A. Rosti G. Castagnetti F. Poerio A. et al. (2006) Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res 12: 7374–7379.
60. Soverini S. de Benedittis C. Machova Polakova K. Brouckova A. Horner D. Iacono M. et al. (2013) Unraveling the complexity of tyrosine kinase inhibitor-resistant populations by ultra-deep sequencing of the BCR-ABL kinase Domain. Blood 122: 1634–1648.
61. Soverini S. Gnani A. Colarossi S. Castagnetti F. Abruzzese E. Paolini S. et al. (2009) Philadelphia-positive patients who already harbor imatinib-resistant BCR-ABL kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors. Blood 114: 2168–2171.
62. Soverini S. Gnani A. de Benedittis C. Castagnetti F. Gugliotta G. Iacobucci I. et al. (2011 a) Low-level BCR-ABL mutations are very rare in chronic myeloid leukemia patients who are in major molecular response on first-line nilotinib. Leuk Res 35: 1527–1529.
63. Soverini S. Martinelli G. Rosti G. Bassi S. Amabile M. Poerio A. et al. (2005) ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol 23: 4100–4109.
64. Soverini S. Rosti G. Iacobucci I. Baccarani M. Martinelli G. (2011 b) Choosing the best second-line tyrosine kinase inhibitor in imatinib-resistant chronic myeloid leukemia patients harboring BCR-ABL kinase domain mutations: how reliable is the IC50? Oncologist 16: 868–876.
65. Weisberg E. Manley P. Breitenstein W. Bruggen J. Cowan-Jacob S. Ray A. et al. (2005) Characterization of AMN107, a selective inhibitor of native and mutant BCR-ABL. Cancer Cell 7: 129–141.
66. Weisberg E. Manley P. Cowan-Jacob S. Hockhaus A. Griffin J. (2007) Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 7: 345-356
67. Zhou T. Commodore L. Huang W. Wang Y. Thomas M. Keats J. et al. (2011) Structural mechanism of the pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance. Chem Biol Drug Des 77: 1–11.