Current issues in chronic myeloid leukemia: Monitoring, resistance, and functional cure

JNCCN Journal of the National Comprehensive Cancer Network

Volumn 10, Issue SUPPL.3, 2012, Pages

  Cortes, Jorge ^a   Goldman, John M ^b   Hughes, Timothy ^c  

^a UNIVERSITY OF TEXAS   (United States)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c CENTRE FOR CANCER BIOLOGY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; BCR ABL PROTEIN; BMS 833923; BOSUTINIB; CYTARABINE; DASATINIB; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HOMOHARRINGTONINE; HYDROXYCHLOROQUINE; IMATINIB; LDF 225; NILOTINIB; PEGINTERFERON ALPHA2A; PONATINIB; PROTEIN BCL 6; PROTEIN INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ADD ON THERAPY; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; CANCER CHEMOTHERAPY; CHRONIC MYELOID LEUKEMIA; CLINICAL PRACTICE; CYTOGENETICS; DRUG APPROVAL; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; FLUORESCENCE IN SITU HYBRIDIZATION; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL TOXICITY; GENE MUTATION; HEMATOLOGICAL PARAMETERS; HUMAN; LEUKOCYTE COUNT; LOW DRUG DOSE; NONHUMAN; OUTCOMES RESEARCH; OVERALL SURVIVAL; PATIENT MONITORING; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHILADELPHIA CHROMOSOME POSITIVE CELL; PRACTICE GUIDELINE; PREDICTION; PROGRESSION FREE SURVIVAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SPLENOMEGALY; TREATMENT FAILURE; TREATMENT OUTCOME; TREATMENT RESPONSE;

EID: 84871191881     PISSN: 15401405     EISSN: 15401413     Source Type: Journal    
DOI: 10.6004/jnccn.2012.0184     Document Type: Review

References (73)

1. Savage DG, Antman KH. Imatinib mesylate - a new oral targeted therapy. N Engl J Med 2002;346:683-693. (Pubitemid 34815874)
2. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809-1820. (Pubitemid 44394987)
3. Baccarani M, Cortes J, Pane F, et al. Chronic myelogenous leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041-6051.
4. O'Brien S, Abboud CN, Akhtari M, et al. NCCN Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia. Version 2, 2013. Available at: NCCN.org. Accessed September 17, 2012.
5. Hughes T, Deininger M, Hochhaus A, et al. 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 2006;108:28-37. (Pubitemid 43990609)
6. Cross NC, White HE, Muller MC, et al. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia 2012, in press.
7. O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronicphase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004. (Pubitemid 36302244)
8. Deininger M, O'Brien SG, Guilhot F, et al. International randomized study of interferon vs STI571 (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 [abstract]. Blood 2009;114:Abstract 1126.
9. Marin D, Milojkovic D, Olavarria E, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood 2008;112:4437-4444.
10. Alvarado Y, Kantarjian H, O'Brien S, et al. Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase. Cancer 2009:115:3709-3718.
11. Muller MC, Cross NCP, Erben P, et al. Harmonization of molecular monitoring of CML therapy in Europe. Leukemia 2009;23:1957-1963.
12. Jabbour E, Kantarjian H, O'Brien S, et al. The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood 2011;118:4541-4546.
13. Press RD, Love Z, Tronnes AA, et al. BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. Blood 2006;107:4250-4256. (Pubitemid 43801348)
14. Hughes T, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Rev 2006;20:29-41. (Pubitemid 43106716)
15. Hughes TP, Hochhaus A, Branford S, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 2010;116:3758-3765.
16. Hanfstein B, Muller MC, Erben P, et al. Molecular and cytogenetic response after 3 months of imatinib treatment is predictive for the risk of disease progression and death in newly diagnosed chronic myeloid leukemia patients: a follow-up analysis of the German CML Study IV [abstract]. Blood 2011;118:Abstract 783.
17. Hochhaus A, Saglio G, Chuah C, et al. Dasatinib and imatinib-induced reductions in BCR-ABL transcript levels below 10% at 3 months are associated with improved responses in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): analysis of molecular response kinetics in the DASISION Trial [abstract]. Blood 2011;118:Abstract 2767.
18. Marin D, Ibrahim AM, Lucas C, et al. 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 2012;20:232-238.
19. Marin D, Hedgley C, Clark RE, et al. Predictive value of early molecular response in patients with chronic myeloid leukemia treated with first-line dasatinib. Blood 2012;120:291-294.
20. Shah NP, Kantarjian H, Kim DW, et al. Six-year (yr) follow-up of patients (pts) with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia (CML-CP) receiving dasatinib [abstract]. J Clin Oncol 2012;30(Suppl):Abstract 6506.
21. Branford S, Martinelli G, Saglio G, et al. Association of early molecular response to nilotinib with probability of cytogenetic response in chronic myeloid leukemia patients (pts) who fail imatinib [abstract]. J Clin Oncol 2010;28(Suppl):Abstract 6513.
22. Quintas-Cardama A, Kantarjian HM, Cortes JE. Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control 2009;16:122-131.
23. Bixby D, Talpaz M. Seeking the causes and solutions to imatinib-resistance in chronic myeloid leukemia. Leukemia 2011;25:7-22.
24. White DL, Saunders V, Dang P, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood 2007;110:4064-4072. (Pubitemid 350248463)
25. White DL, Dang P, Engler J, et al. Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib. J Clin Oncol 2010;28:2761-2767.
26. Dulucq S, Bouchet S, Turcq B, et al. Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 2008;112:2024-2027.
27. Donato NJ, Wu JY, Stapley J, et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 2003;101:690-698. (Pubitemid 36077594)
28. Mahon FX, Hayette S, Lagarde V, et al. Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer Res 2008;68:9809-9816.
29. Soverini S, Colarossi S, Gnani A, et al. 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 2006;12:7374-7379. (Pubitemid 46095411)
30. Hochhaus A, Kantarjian HM, Baccarani M, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 2007;109:2303-2309. (Pubitemid 46425867)
31. Nicolini FE, Comm S, Le QH, et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(u)-LMC GROUP). Leukemia 2006;20:1061-1066. (Pubitemid 43797298)
32. Pagnano KB, Bendit I, Boquimpani C, et al. Bcr-Abl mutations in chronic myeloid leukemia: impact on survival and treatment with second generation inhibitors. A study on behalf of Latin American Leukemia Net (Lalnet) [abstract]. Blood 2011;118:Abstract 1701.
33. Piazza RG, Magistroni V, Andreoni F, et al. Imatinib dose increase up to 1200 mg daily can induce new durable complete cytogenetic remissions in relapsed Ph+ chronic myeloid leukemia patients. Leukemia 2005;16:1985-1987. (Pubitemid 41554008)
34. Brave M, Goodman V, Kaminskas E, et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res 2008;14:352-359. (Pubitemid 351226100)
35. Kantarjian H, Giles F, Bhalla K, et al. Update on imatinib-resistant chronic myeloid leukemia patients in chronic phase (CML-CP) on nilotinib therapy at 24 months: clinical response, safety, and long-term outcomes [abstract]. Blood 2009;114:Abstract 1129.
36. Branford S, Melo JV, Hughes TP. Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter? Blood 2009;114:5426-5435.
37. Parker WT, Lawrence RM, Ho M, et al. Sensitive detection of BCR-ABL1 mutations in patients with chronic myeloid leukemia after imatinib resistance is predictive of outcome during subsequent therapy. J Clin Oncol 2011;29:4250-4259.
38. Saglio G, Kim DW, Issaragrasil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-2259.
39. Kantarjian H, Flinn IW, Goldberg S, et al. Nilotinib versus imatinib in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd 3-year (yr) follow-up (f/u) [abstract]. J Clin Oncol 2012;30(Suppl):Abstract 6509.
40. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-2270.
41. Hochhaus A, Shah NP, Cortes JE, et al. Dasatinib versus imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): DASISION 3-year follow-up [abstract]. J Clin Oncol 2012;30(Suppl):Abstract 6504.
42. Radich JP, Kopecky KJ, Kamel-Reid S, et al. A randomized phase ii trial of dasatinib 100 mg vs imatinib 400 mg in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): the S0325 Intergroup trial [abstract]. Blood 2010;116:Abstract LBA-6.
43. Lipton JH, Hughes TP, Leber B, et al. Switch to nilotinib versus continued imatinib in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) with detectable BCR-ABL after 2 or more years on imatinib: ENESTcmr 12-month (mo) follow-up [abstract]. J Clin Oncol 2012;30(Suppl): Abstract 6505.
44. O'Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 2009;16:401-412.
45. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Initial findings from the PACE trial: a pivotal phase 2 study of ponatinib in patients with CML and Ph+ ALL resistant or intolerant to dasatinib or nilotinib, or with the t315i mutation [abstract]. Blood 2011;118:Abstract 109.
46. Chen Y, Hu Y, Michaels S, et al. Inhibitor effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice. Leukemia 2009;23:1446-1454.
47. Nicolini F, Legros L, Roy L, et al. Homo-harringtonine (omacetaxine mepesuccinate) induces a dramatic and sustained reduction of BCR-ABLT315I mutated transcripts in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors [abstract]. Blood 2008;112:Abstract 450.
48. Nanda N, Cortes J, Lipton J, et al. Treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients who harbor the BCR-ABL T315I mutation with subcutaneous omacetaxine results in improved survival compared to historical data [abstract]. Haematologica 2011;96(Suppl 2):Abstract 1012.
49. Cortes-Franco J, Raghunadharao D, Parikh P, et al. Safety and efficacy of subcutaneous-administered omacetaxine mepesuccinate in chronic myeloid leukemia (CML) patients who are resistant or intolerant to two or more tyrosine kinase inhibitors - results of a multicenter phase 2/3 study [abstract]. Blood 2009;114:Abstract 861.
50. Cortes JE, Nicolini FE, Wetzler M, et al. Subcutaneous omacetaxine in chronic or accelerated chronic myeloid leukemia resistant to two or more tyrosine-kinase inhibitors including imatinib [abstract]. Blood 2011;118:Abstract 3761.
51. Nicolini FE, Lipton JH, Kantarjian H, et al. Subcutaneous omacetaxine mepesuccinate in patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) resistant/intolerant to two or three approved tyrosine-kinase inhibitors (TKIs) [abstract]. J Clin Oncol 2012;30(Suppl): Abstract 6513.
52. Golas JM, Arndt K, Etienne C, et al. 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 K562 xenografts in nude mice. Cancer Res 2003;63:375-381. (Pubitemid 36152495)
53. Khoury HJ, Cortes JE, Gambacorti-Passerini C, et al. Activity of bosutinib by baseline and emergent mutation status in Philadelphia chromosome-positive leukemia patients with resistance or intolerance to other tyrosine kinase inhibitors [abstract]. Blood 2011;118:Abstract 110.
54. Khoury HJ, Cortes JE, Kantarjian HM, et al. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood 2012;119:3403-3412.
55. Cortes JE, Maru A, De Souza CAA, et al. Bosutinib versus imatinib in newly diagnosed chronic phase chronic myeloid leukemia - BELA Trial: 24-month follow-up [abstract]. Blood 2011;118:Abstract 455.
56. Gambacorti-Passerini C, Lipton JH, Tee GY, et al. BELA trial update: bosutinib (BOS) versus imatinib (IM) in patients (pts) with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) after 30 months of follow-up [Abstract]. J Clin Oncol 2012;30(Suppl):Abstract 6512.
57. Saussele S, Lauseker M, Gratwohl A, et al. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood 2010;115:1880-1885.
58. Jabbour E, Cortes J, Santos FPS, et al. Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations. Blood 2011;117:3641-3647.
59. Goldman JM, Gordon MY. Why do stem CML cells survive allogeneic stem cell transplantation or imatinib? Does it really matter? Leuk Lymphoma 2006;47:1-8.
60. Melo JV, Ross DM. Minimal residual disease and discontinuation of therapy in chronic myeloid leukemia: can we aim at a cure? Hematology Am Soc Hematol Educ Program 2011;2011:136-142.
61. Mahon FX, Delbrel X, Cony-Makhoul P, et al. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J Clin Oncol 2002;20:214-220. (Pubitemid 34032614)
62. Kantarjian HM, O'Brien S, Cortes JE, et al. Complete cytogenetic and molecular responses to interferon-alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer 2003;97:1033-1041. (Pubitemid 36173155)
63. Mahon F-X, Réa D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029-1035.
64. Mahon F-X, Réa D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukemia who have maintained complete molecular response: update results of the STIM study [abstract]. Blood 2011;118:Abstract 603.
65. Ross M, Branford S, Seymour J, et al. Frequent and sustained drug-free remission in the Australasian CML8 trial of imatinib withdrawal [abstract]. Haemaologica 2012;97(Suppl 1):Abstract 0180.
66. Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus peginterferon alfa-21 in chronic myeloid leukemia. N Engl J Med 2010;363:2511-2521.
67. Simonnson B, Gedde-Dahl T, Markevam B, et al. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood 2011;118:3228-3236.
68. Hehlmann R, Lauseker M, Jung-Munkwitz S, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-α in newly diagnosed chronic myeloid leukemia. J Clin Oncol 2011;29:1634-1642.
69. Cortes J, Quintas-Cardama A, Jones D, et al. Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia: a randomized trial of frontline high-dose imatinib mesylate with or without pegylated interferon alpha-2b and granulocyte-macrophage colony-stimulating factor. Cancer 2011;117:572-580.
70. Helgason GV, Karvela M, Holyoake TL. Kill one bird with two stones: potential efficacy of BCR-ABL and autophagy inhibition in CML. Blood 2011;118:2035-2043.
71. Irvine DA, Zhang B, Allan EK, et al. Combination of the hedgehog pathway inhibitor LDE225 and nilotinib eliminates chronic myeloid leukemia stem and progenitor cells [abstract]. Blood 2009;114:Abstract 1428.
72. Jagani Z, Dorsch M, Warmuth M. Hedgehog pathway activation in chronic myeloid leukemia. A promise for a novel combination therapeutic approach? Cell Cycle 2010;9:3449-3456.
73. Hurtz C, Hatzi K, Cerchietti L, et al. BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia. J Exp Med 2011;208:2163-2174.