Molecular monitoring to improve outcomes in patients with chronic myeloid leukemia in chronic phase: Importance of achieving treatment-free remission

American Journal of Hematology

Volumn 90, Issue 3, 2015, Pages 242-249

  Erba, Harry P ^a  

^a Heerskink School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMATINIB; INTERFERON; PROTEIN TYROSINE KINASE INHIBITOR; ANTINEOPLASTIC AGENT; BCR ABL PROTEIN; BCR-ABL1 FUSION PROTEIN, HUMAN; BENZAMIDE DERIVATIVE; PHARMACOLOGICAL BIOMARKER; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRIMIDINE DERIVATIVE;

CANCER PATIENT; CANCER PROGNOSIS; CANCER RISK; CHRONIC DISEASE; CHRONIC MYELOID LEUKEMIA; HUMAN; LEUKEMIA RELAPSE; LEUKEMIA REMISSION; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STEM CELL; TREATMENT FREE REMISSION; TREATMENT OUTCOME; TREATMENT RESPONSE; ANTAGONISTS AND INHIBITORS; DRUG MONITORING; GENETICS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; METABOLISM; PATHOLOGY; PROGNOSIS; REMISSION;

ANTINEOPLASTIC AGENTS; BENZAMIDES; BIOMARKERS, PHARMACOLOGICAL; DRUG MONITORING; FUSION PROTEINS, BCR-ABL; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; PIPERAZINES; PROGNOSIS; PROTEIN KINASE INHIBITORS; PYRIMIDINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REMISSION INDUCTION;

EID: 84923075854     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.23902     Document Type: Review

References (66)

1. Shtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985;315:550-554.
2. Kurzrock R, Gutterman JU, Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med 1988;319:990-998.
3. Tkachuk DC, Westbrook CA, Andreeff M, et al. Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization. Science 1990;250:559-562.
4. O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004.
5. 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. Blood 2009;114 (abstr 1126).
6. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-2259.
7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Chronic Myelogenous Leukemia. V1.2015. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Accessed on October 16, 2014.
8. 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.
9. Marin D, Ibrahim AR, 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;30:232-238.
10. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041-6051.
11. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013;122:872-884.
12. Kantarjian H, O'Brien S, Jabbour E, et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: A single-institution historical experience. Blood 2012;119:1981-1987.
13. Chen Y, Wang H, Kantarjian H, Cortes J. Trends in chronic myeloid leukemia incidence and survival in the United States from 1975 to 2009. Leuk Lymphoma 2013;54:1411-1417.
14. 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.
15. Kantarjian HM, Hochhaus A, Saglio G, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol 2011;12:841-851.
16. Larson RA, Kim DW, Jootar S, et al. ENESTnd 5-y update: Long-term outcomes of patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline nilotinib (NIL) vs imatinib (IM). J Clin Oncol 2014;32 (abstr 7073).
17. Cortes JE, Hochhaus A, Kim DW, et al. Four-year (yr) follow-up of patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) receiving dasatinib or imatinib: Efficacy based on early response. Blood 2013;122 (abstr 653).
18. Ibrahim AR, Eliasson L, Apperley JF, et al. Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long term therapy. Blood 2011;117:3733-3736.
19. Kantarjian H, Cortes J. Considerations in the management of patients with Philadelphia chromosome-positive chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy. J Clin Oncol 2011;29:1512-1516.
20. Hehlmann R, Müller MC, Lauseker M, et al. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: Results from the randomized CML-Study IV. J Clin Oncol 2014;32:415-423.
21. Hughes TP, Saglio G, Kantarjian HM, et al. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood 2014;123:1353-1360.
22. Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood 2014;123:494-500.
23. Brummendorf TH, Kantarjian HM, Gambacorti-Passerini C, et al. Assessment of early molecular response as a predictor of long-term clinical outcomes in the phase 3 BELA study. Blood 2012;120:69.
24. 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.
25. Branford S, Fletcher L, Cross NC, et al. Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood 2008;112:3330-3338.
26. Cross NC, White HE, Muller MC, et al. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia 2012;26:2172-2175.
27. Ross DM, Branford S, Seymour JF, et al. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia 2010;10:1719-1724.
28. Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: Results from the TWISTER study. Blood 2013;122:515-522.
29. Falchi L, Kantarjian HM, Wang X, et al. Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J Hematol 2013;88:1024-1029.
30. Chen L, Guerin A, Xie J, et al. Monitoring and switching patterns of patients with chronic myeloid leukemia treated with imatinib in community settings: A chart review analysis. Curr Med Res Opin 2012;28:1831-1839.
31. Goldberg SL, Chen L, Guerin A, et al. Association between molecular monitoring and long term outcomes in chronic myelogenous leukemia patients treated with first line imatinib. Curr Med Res Opin 2013;29:1075-1082.
32. Hanfstein B, Muller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 2012;26:2096-2102.
33. Branford S, Kim DW, Soverini S, et al. Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib. J Clin Oncol 2012;30:4323-4329.
34. Kim DD, Lee H, Kamel-Reid S, Lipton JH. BCR-ABL1 transcript at 3 months predicts long-term outcomes following second generation tyrosine kinase inhibitor therapy in the patients with chronic myeloid leukaemia in chronic phase who failed Imatinib. Br J Haematol 2013;160:630-639.
35. Etienne G, Dulucq S, Nicolini FE, et al. Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib frontline therapy. Haematologica 2014;99:458-464.
36. 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.
37. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med 1994;330:820-825.
38. Talpaz M, Kantarjian H, Kurzrock R, et al. Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia: Philadelphia chromosome-positive patients. Ann Intern Med 1991;114:532-538.
39. Hehlmann R, Heimpel H, Hasford J, et al. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. Blood 1994;84:4064-4077.
40. Ohnishi K, Ohno R, Tomonaga M, et al. A randomized trial comparing interferon-alpha with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase. Blood 1995;86:906-916.
41. 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.
42. 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.
43. Mauro MJ, Druker BJ, Maziarz RT. Divergent clinical outcome in two CML patients who discontinued imatinib therapy after achieving a molecular remission. Leuk Res 2004;28:S71-S73.
44. Rousselot P, Huguet F, Rea D, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 2007;109:58-60.
45. Mahon FX, Rea 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.
46. Mahon FX, Rea D, Guilhot J, et al. Long term follow-up after imatinib cessation for patients in deep molecular response: The update results of the STIM1 study. Blood 2013;122 (abstr 255).
47. Kuwabara A, Babb A, Ibrahim A, et al. Poor outcome after reintroduction of imatinib in patients with chronic myeloid leukemia who interrupt therapy on account of pregnancy without having achieved an optimal response. Blood 2010;116:1014-1016.
48. Goh HG, Kim YJ, Kim DW, et al. Previous best responses can be re-achieved by resumption after imatinib discontinuation in patients with chronic myeloid leukemia: Implication for intermittent imatinib therapy. Leuk Lymphoma 2009;50:944-951.
49. Koskenvesa P, Mustjoki S, Rasanen A, et al. Imatinib discontinuation following a major molecular response: Impact of interferon alpha and leukemia stem cell burden (the STOP study). Blood 2008;112 (abstr 2121).
50. Merante S, Orlandi E, Bernasconi P, et al. Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation. Haematologica 2005;90:979-981.
51. Rousselot P, Charbonnier A, Cony-Makhoul P, et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol 2014;32:424-430.
52. Lee SE, Choi SY, Bang JH, et al. Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib. Am J Hematol 2013;88:449-454.
53. Branford S, Yeung DT, Ross DM, et al. Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML. Blood 2013;121:3818-3824.
54. Spector N, Clementino NCD, Dorlhiac-Llacer PE, et al. Effect of continued imatinib (IM) in pts with detectable BCR-ABL after≥2 years on study on deep molecular responses (MR): 36-month update from ENESTcmr. J Clin Oncol 2014;32 (abstr 7025).
55. Rea D, Rousselot P, Guilhot F, et al. Discontinuation of second generation (2G) tyrosine kinase inhibitors (TKI) in chronic phase (CP)-chronic myeloid leukemia (CML) patients with stable undetectable BCR-ABL transcripts. Blood 2012;120 (abstr 916).
56. Bonifazi F, de Vivo A, Rosti G, et al. Chronic myeloid leukemia and interferon-alpha: A study of complete cytogenetic responders. Blood 2001;98:3074-3081.
57. Mahon FX, Baccarani M, Mauro MJ, et al. Treatment-free remission (TFR) following nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTfreedom, ENESTop, ENESTgoal, and ENESTpath. J Clin Oncol 2014;32 (abstr TPS7124).
58. Saussele S, Richter J, Guilhot J, et al. First interim analysis of a pan-European STOP trial using standardized molecular criteria: Results of the EURO-SKI trial. Haematologica 2014;99 (abstr LB2440).
59. Kimura S, Imagawa J, Okada M, et al. Discontinuation of dasatinib in patients with CML who have maintained complete molecular response for at least one year: Results from a prospective discontinuation (DADI) trial. Haematologica 2014;99 (abstr P289).
60. Graham SM, Jorgensen HG, Allan E, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 2002;99:319-325.
61. Jorgensen HG, Allan EK, Jordanides NE, et al. Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells. Blood 2007;109:4016-4019.
62. Copland M, Hamilton A, Elrick LJ, et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 2006;107:4532-4539.
63. Dierks C, Beigi R, Guo GR, et al. Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell 2008;14:238-249.
64. Zhao C, Chen A, Jamieson CH, et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 2009;458:776-779.
65. David A, Zhang B, Ho Y, et al. Combination of the hedgehog pathway inhibitor LDE225 and nilotinib targets the leukemic stem cell population in chronic myeloid leukaemia. Haematologica 2011;96:221 (abstr 0521).
66. Chen M, Gallipoli P, DeGeer D, et al. Targeting primitive chronic myeloid leukemia cells by effective inhibition of a new AHI-1-BCR-ABL-JAK2 complex. J Natl Cancer Inst 2013;105:405-423.