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Expert Review of Anticancer Therapy Volume 13, 2013 - Issue 12
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Theme: General - Reviews

Tyrosine kinase inhibition: a therapeutic target for the management of chronic-phase chronic myeloid leukemia

Elias J JabbourThe University of Texas, MD Anderson Cancer Center, Houston, TX, USACorrespondence[email protected]
,
Jorge E CortesThe University of Texas, MD Anderson Cancer Center, Houston, TX, USA
&
Hagop M KantarjianThe University of Texas, MD Anderson Cancer Center, Houston, TX, USA
Pages 1433-1452 | Published online: 10 Jan 2014

References

  • Druker BJ, Guilhot F, O'Brien SG et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 355(23), 2408–2417 (2006).
  • Baccarani M, Pileri S, Steegmann J-L et al.; ESMO Guidelines Working Group. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 23(Suppl. 7), vii72–vii77 (2012).
  • Bartram CR, de Klein A, Hagemeijer A et al. Translocation of c-ab 1 oncogene correlates with the presence of a Philadelphia chromosome in chronic myelogenous leukemia. Nature 306(5940), 277–280 (1983).
  • Shtalrid M, Talpaz M, Blick M et al. Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy. J. Clin. Oncol. 6(10), 1569–1575 (1988).
  • Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat. Rev. Cancer 5(3), 172–183 (2005).
  • Thielen N, Ossenkoppele GJ, Schuurhuis G-J, Janssen JJ. New insights into the pathogenesis of chronic myeloid leukemia: towards a path to cure. Neth. J. Med. 69(10), 430–440 (2011).
  • Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds). WHO Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, Lyon, France (2001).
  • Kantarjian HM, Deisseroth A, Kurzrock R, Estrov Z, Talpaz M. Chronic myelogenous leukemia: a concise update. Blood 82(3), 691–703 (1993).
  • Swerdlow SH, Campo E, Harris NL et al. (Eds). WHO Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, Lyon, France (2008).
  • Calabretta B, Perrotti D. The biology of CML blast crisis. Blood 103(11), 4010–4022 (2004).
  • Sokal JE, Baccarani M, Russo D, Tura S. Staging and prognosis in chronic myelogenous leukemia. Semin. Hematol. 25(1), 49–61 (1988).
  • Quintas-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin. Proc. 81(7), 973–988 (2006).
  • O'Brien S, 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. 348(11), 994–1004 (2003).
  • Hughes TP, Kaeda J, Branford S et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 349(15), 1423–1432 (2003).
  • Faderl S, Kurzrock R, Estrov Z. Chronic myelogenous leukemia: biology and therapy. Ann. Intern. Med. 131(3), 207–219 (1999).
  • Baccarani M, Deininger MW, Rosti G et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122(6), 872–884 (2013).
  • Hochhaus A, O'Brien SG, Guilhot F et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 23(6), 1054–1061 (2009).
  • Deininger M, O'Brien SG, Guilhot F et al. International randomized study of interferon vs ST1571 (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. Presented at: American Society of Hematology 51st Annual Meeting. New Orleans, LA, USA, 5–8 December 2009. Blood 114(22), Abstract 1126 (2009).
  • Gambacorti-Passerini C, Antolini L, Mahon FX et al. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J. Natl Cancer Inst. 103(7), 553–561 (2011).
  • Cortes JE, Jones D, O'Brien S, Jabbour E. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J. Clin. Oncol. 28(3), 398–404 (2010).
  • Fullmer A, Kantarjian H, Cortes J et al. Nilotinib for the treatment of Philadelphia-chromosome-positive chronic myeloid leukemia. Expert Opin. Pharmacother. 11(18), 3065–3072 (2010).
  • Saglio G, Kim DW, Issaragrisil SM et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 362(24), 2251–2259 (2010).
  • 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. 12(9), 841–851 (2011).
  • Larson RA, Hochhaus A, Hughes TP et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 26(10), 2197–2203 (2012).
  • Hochhaus A, Saglio G, Larson R et al. Nilotinib shows sustained benefit compared with imatinib in patients (Pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd 4-year follow-up (F/U). Presented at: 18th Congress of the European Hematology Association. Stockholm, Sweden, 13–16 June 2013. Haematologica 98(Suppl. 1), Abstract P712 (2013).
  • Kantarjian HM, Shah NP, Hochhaus A et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 362(24), 2260–2270 (2010).
  • Kantarjian HM, Shah NP, Cortes JE et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 119(5), 1123–1129 (2012).
  • 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. Presented at: American Society of Clinical Oncology Annual Meeting. Chicago, IL, USA, 1–5 June 2012. J. Clin. Oncol. 30(Suppl.), Abstract 6504 (2012).
  • Cortes JE, Kim DW, Kantarjian HM et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J. Clin. Oncol. 30(28), 3486–3492 (2012).
  • 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. Presented at: American Society of Clinical Oncology Annual Meeting. Chicago, IL, USA, 1–5 June 2012. J. Clin. Oncol. 30(Suppl.), Abstract 6512 (2012).
  • de Lavallade H, Apperley JF, Khirashad JS et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J. Clin. Oncol. 26(20), 3358–3363 (2008).
  • Lucas CM, Wang L, Austin GM et al. A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials. Leukemia 22(10), 1963–1966 (2008).
  • Michallet M, Tulliez M, Corm S et al. Management of chronic myeloid leukaemia in clinical practice in France: results of the French subset of patients from the UNIC study. Curr. Med. Res. Opin. 26(2), 307–317 (2010).
  • Kantarjian HM, O'Brien S, Jabbour E et al. Impact of treatment end point definitions on perceived differences in long-term outcome with tyrosine kinase inhibitor therapy in chronic myeloid leukemia. J. Clin. Oncol. 29(23), 3173–3178 (2011).
  • Fava C, Kantarjian HM, Jabbour E et al. Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase. Blood 113(21), 5058–5063 (2009).
  • Jabbour E, Cortes JE, Kantarjian HM. Molecular monitoring in chronic myeloid leukemia: response to tyrosine kinase inhibitors and prognostic implications. Cancer 112(10), 2112–2118 (2008).
  • Jabbour E, Kantarjian H, O'Brien S et al. The achievement of an early complete cytogenetic response is a major determinant of outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood 118(17), 4541–4546 (2011).
  • Guilhot F, Druker B, Larson RA et al. High rates of durable response are achieved with imatinib after treatment with interferon alpha plus cytarabine: results from the International Randomized Study of Interferon and STI571 (IRIS) trial. Haematologica 94(12), 1669–1675 (2009).
  • Jabbour E, Kantarjian HM, O'Brien S et al. Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia: what is the optimal response? J. Clin. Oncol. 29(32), 4260–4265 (2011).
  • 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 112(12), 4437–4444 (2008).
  • Hughes T, 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 116(19), 3758–3765 (2010).
  • Kantarjian H, O'Brien S, Shan J et al. Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia. Need for new response definitions? Cancer 112(4), 837–845 (2008).
  • 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. 29(12), 1634–1642 (2011).
  • 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) (Epub ahead of print).
  • Kantarjian HM, Shan J, Jones D et al. Significance of increasing levels of minimal residual disease in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic response. J. Clin. Oncol. 27(22), 3659–3663 (2009).
  • 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 26(9), 2096–2102 (2012).
  • Saglio G, Kantarjian HM, Shah N et al. 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. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 1675 (2012).
  • 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 120(2), 291–294 (2012).
  • Hochhaus A, Hughes TP, Saglio G et al. 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). Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 167 (2012).
  • Rousselot P, Guilhot J, Preudhomme C et al. Relationship between molecular responses and disease progression in patients (pts) treated first line with imatinib (Im) based regimens: impact of treatment arm within the French Spirit trial from the French CML group (FI LMC). Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 168 (2012).
  • 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. 30(3), 232–238 (2012).
  • Neelakantan P, Gerrard G, Foroni L et al. Can the combination of the measurement of BCR-ABL1 transcript levels at 3 and 6 months improve the prognostic value of the 3 month measurement? Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 68 (2012).
  • Jain P, Kantarjian HM, Nazha A et al. Early molecular and cytogenetic responses predicts for significantly longer event free survival (EFS) and overall survival (OS) in patients (pts) with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) – an analysis of 4 tyrosine kinase inhibitor (TKI) modalities (standard dose imatinib, high dose imatinib, dasatinib and nilotinib). Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 70 (2012).
  • Hughes T, Branford S, White DL et al. Impact of early dose intensity on cytogenetic and molecular responses in chronic-phase CML patients receiving 600 mg/day of imatinib as initial therapy. Blood 112(10), 3965–3973 (2008).
  • Kantarjian HM, Talpaz M, O'Brien S et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood 103(8), 2873–2878 (2004).
  • Cortes JE, Kantarjian HM, Goldberg SL et al. High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses. J. Clin. Oncol. 27(28), 4754–4759 (2009).
  • Castagnetti F, Palandri F, Amabie M et al. Results of high dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase 2 trial of the GIMEMA CML Working Party. Blood 113(15), 3428–3434 (2009).
  • Baccarani M, Rosti G, Castagnetti F et al. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study. Blood 113(19), 4497–4504 (2009).
  • Cortes JE, Baccarani M, Guilhot F et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. J. Clin. Oncol. 28(3), 424–430 (2010).
  • Hehlmann R, Lauseker M, Hanfstein B et al. Complete molecular remission (CMR4.5) of CML is induced faster by dose-optimized imatinib and predicts better survival – results from the randomized CML-Study IV. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 67 (2012).
  • Breccia M, Alimena G. Second-generation tyrosine kinase inhibitors as first-line treatment strategy in newly diagnosed chronic phase chronic myeloid leukemia patients. Curr. Cancer Drug Targets 12(4), 391–401 (2012).
  • Katouli AA, Komarova NL. Optimizing combination therapies with existing and future CML drugs. PLoS One 5, e12300 (2010).
  • Komarova NL, Katouli AA, Wodarz D. Combination of two but not three current targeted drugs can improve therapy of chronic myeloid leukemia. PLoS One 4:e4423 (2009).
  • Cortes JE, 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 117(3), 572–580 (2011).
  • Simonsson B, Gedde-Dahl T, Markevarn 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 118(12), 3228–3235 (2011).
  • Preudhomme C, Guilhot J, Nicolini FE et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N. Engl. J. Med. 363(26), 2511–2521 (2010).
  • Lipton JH, Khoroshko N, Golenkov A et al. Phase II, randomized, multicenter, comparative study of peginterferon-alpha-2a (40 kD) (Pegasys) versus interferon alpha-2a (Roferon-A) in patients with treatment-naïve, chronic-phase chronic myelogenous leukemia. Leuk. Lymphoma 48(3), 497–505 (2007).
  • Nicolini FE, Etienne G, Dubruille V et al. Pegylated interferon-α 2a in combination to nilotinib as first line therapy in newly diagnosed chronic phase chronic myelogenous leukemia provides high rates of MR4.5. Preliminary results of a Phase II study. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 166 (2012).
  • Eliasson L, Clifford S, Barber N, Marin D. Exploring chronic myeloid leukemia patients’ reasons for not adhering to the oral anticancer drug imatinib as prescribed. Leuk. Res. 35(5), 626–630 (2011).
  • Cross TJ, Bagot C, Portmann B et al. Imatinib mesylate as a cause of acute liver failure. Am. J. Hematol. 81(3), 189–192 (2006).
  • Mindikoglu AL, Regev A, Bejarano PA et al. Imatinib mesylate (Gleevec) hepatotoxicity. Dig. Dis. Sci. 52(2), 598–601 (2007).
  • Montani D, Bergot E, Gunther S et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 125(17), 2128–2137 (2012).
  • Sano M, Saotome M, Urushida T et al. Pulmonary arterial hypertension caused by treatment with dasatinib for chronic myeloid leukemia -critical alert-. Intern. Med. 51(17), 2337–2340 (2012).
  • Le Coutre P, Rea D, Abruzzese E et al. Severe peripheral arterial disease during nilotinib therapy. J. Natl Cancer Inst. 103(17), 1347–1348 (2011).
  • Gambacorti-Passerini C, Zucchetti M, Russo D et al. Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients. Clin. Cancer Res. 9(2), 625–632 (2003).
  • Soverini S, Martinelli G, Rosti G et al. 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(18), 4100–4109 (2005).
  • Wei G, Rafiyath S, Liu D. First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib. J. Hematol. Oncol. 3, 47 (2010).
  • Marin D, Bazeos A, Mahon FX et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J. Clin. Oncol. 28(14), 2381–2388 (2010).
  • Darkow T, Henk HJ, Thomas SK et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 25(6), 481–496 (2007).
  • Noens L, van Lierde MA, De Bock R et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood 113(22), 5401–5411 (2009).
  • 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 101(2), 690–698 (2003).
  • Donato NJ, Wu JY, Stapley J et al. Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia. Cancer Res. 64(2), 672–677 (2004).
  • Wu J, Meng F, Lu H et al. Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Chl protein stability in imatinib-resistant chronic myelogenous leukemia cells. Blood 111(7), 3821–3829 (2008).
  • Hu Y, Swerdlow S, Duffy TM et al. Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc. Natl Acad. Sci. USA 103(45), 16870–16875 (2006).
  • Pene-Dumitrescu T, Peterson LF, Donato NJ, Smithgall TE. An inhibitor-resistant mutant of Hck protects CML cells against the antiproliferative and apoptotic effects of the broad-spectrum Src family kinase inhibitor A-419259. Oncogene 27(56), 7055–7069 (2008).
  • Hayette S, Chabane K, Michallet M et al. Longitudinal studies of SRC family kinases in imatinib- and dasatinib-resistant chronic myelogenous leukemia patients. Leuk. Res. 35(1), 38–43 (2011).
  • Wu J, Meng F, Kong LY et al. Association between imatinib-resistant BCR-ABL mutation-negative leukemia and persistent activation of LYN kinase. J. Natl Cancer Inst. 100(13), 926–939 (2008).
  • Jabbour E, Fullmer A, Cortes JE, Kantarjian H. Clinical algorithms for the treatment of patients with chronic myeloid leukemia: the 2010 perspective. Clin. Lymphoma Myeloma Leuk. 10(Suppl 1), S6–S13 (2010).
  • Kantarjian HM, Larson RA, Guilhot F et al. Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase. Cancer 115(3), 551–560 (2009).
  • Hyun-Gyung G, Jootar S, Kim HJ et al. Efficacy of nilotinib versus high-dose imatinib in early chronic phase CML patients who have suboptimal molecular responses to standard dose imatinib (RE-NICE Multicenter Study). Presented at: American Society of Hematology 53rd Annual Meeting. San Diego, CA, USA, 10–13 December 2011. Blood 118(21), Abstract 2765 (2011).
  • Jabbour E, Kantarjian E, Shan J et al. The achievement of a 3-month complete cytogenetic response (3-mo CCyR) to second generation (2nd) tyrosine kinase inhibitors (TKI) post imatinib failure is the only predictive factor for event-free (EFS) and overall survival (OS). Presented at: American Society of Hematology 52nd Annual Meeting. Orlando, FL, USA, 4–7 December 2010. Blood 116(21), Abstract 2289 (2010).
  • Yeung DT, Osborn M, White DL et al. Upfront imatinib therapy in CML patients with rapid switching to nilotinib for failure to achieve molecular targets or intolerance achieves high overall rates of molecular response and a low risk of progression – an update of the TIDEL-II trial. Presented at: American Society of Hematology 53rd Annual Meeting. San Diego, CA, USA, 10–13 December 2011. Blood 118(21), Abstract 451 (2011).
  • Yeung DT, Osborn MP, White DL et al. Early switch to nilotinib does not overcome the adverse outcome for CML patients failing to achieve early molecular response on imatinib, despite excellent overall outcomes in the TIDEL II trial. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 3771 (2012).
  • 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 119(15), 3403–3412 (2012).
  • Cortes JE, Kantarjian HM, Brummendorf TH et al. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 118(17), 4567–4576 (2011).
  • Cortes JE, Kantarjian HM, Kim DW et al. Bosutinib as therapy for chronic phase chronic myeloid leukemia following resistance or intolerance to imatinib: 36-month minimum follow-up update. American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 3779 (2012).
  • Cortes JE, Kim DW, Pinilla-Ibarz J et al. PACE: 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 mutation: 12-month follow-up of the PACE trial. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 163 (2012).
  • Allan EK, Holyoake TL, Craig AR, Jørgensen HG. Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells. Leukemia 25(6), 985–994 (2011).
  • Ayoubi M, Kantarjan HM, Wierda W et al. A Phase 2 study of the combination of omacetaxine and imatinib in the treatment of patients with chronic myeloid leukemia (CML) in advanced stages or after failure to imatinib. Presented at: American Society of Hematology 51st Annual Meeting. New Orleans, LA, USA, 5–8 December 2009. Blood 114(22), Abstract 2193 (2009).
  • 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. Presented at: American Society of Hematology 51st Annual Meeting. New Orleans, LA, USA, 5–8 December 2009. Blood 114(22), Abstract 861 (2009).
  • 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. Presented at: American Society of Hematology 53rd Annual Meeting. San Diego, CA, USA, 10–13 December 2011. Blood 118(21), Abstract 3761 (2011).
  • Cortes J, Lipton JH, Rea D et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood 120(13), 2573–2580 (2012).
  • Kantarjian HM, Lipton JH, Baccarani M et al. Long-term follow-up of ongoing patients in 2 studies of omacetaxine mepesuccinate for chronic myeloid leukemia. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 2787 (2012).
  • Chen Y, Hu Y, Michaels S et al. Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice. Leukemia 23(8), 1446–1454 (2009).
  • 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. 11(11), 1029–1035 (2010).
  • Mahon FX, Rea 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. Presented at: American Society of Hematology 53rd Annual Meeting. San Diego, CA, USA, 10–13 December 2011. Blood 118(21), Abstract 603 (2011).
  • Ross M, 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 122(4), 515–522 (2013).
  • Takahashi N, Kyo T, Maeda Y et al. Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia. Haematologica 97(6), 903–906 (2012).
  • Legros L, Rousselot P, Giraudier S et al. Second attempt to discontinue imatinib in CP-CML patients with a second sustained complete molecular response. Blood 120(9), 1959–1960 (2012).
  • Ross DM, Bartley PA, Goyne J et al. Durable complete molecular remission of chronic myeloid leukemia following dasatinib cessation, despite adverse disease features. Haematologica 96(11), 1720–1722 (2011).
  • 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. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 916 (2012).
  • Usuki k, Yusa N, Hangaishi A et al. Sustained molecular response with maintenance dose of interferon alfa after imatinib discontinuation in patients with chronic myeloid leukemia. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 1684 (2012).
  • Burchert A, Müller MC, Kostrewa P et al. Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia. J. Clin. Oncol. 28(8), 1429–1435 (2010).
  • Branford S, Ross D, Prime J et al. Early molecular response and female sex strongly predict achievement of stable undetectable BCR-ABL1, a criterion for imatinib discontinuation in patients with CML. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 165 (2012).
  • Matsuki E, Ono Y, Tonegawa K et al. Detailed investigation on characteristics of Japanese patients with chronic phase CML who achieved a durable CMR after discontinuation of imatinib – an updated result of the Keio STIM study. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 2788 (2012).
  • Ohyashiki K, Katagiri S, Tauchi T et al. Increased natural killer cells and decreased CD3+CD8+CD62L+ T cells in CML patients who sustained complete molecular remission after discontinuation of imatinib. Br. J. Haematol. 157(2), 254–256 (2012).
  • Katagiri S, Mizoguchi I, Yoshimoto T et al. Activation levels of natural killer cells and CD8+ T cells correlate highly with sustained complete molecular response after discontinuation of imatinib in chronic myeloid leukemia patients. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 3745 (2012).
  • Kyle RMA, Lazo-Langner A, Xenocostas A et al. Patient preferences for stopping tyrosine kinase inhibitors in chronic myeloid leukemia. Presented at: American Society of Hematology 54th Annual Meeting. Atlanta, GA, USA, 8–11 December 2012. Blood 120(21), Abstract 4274 (2012).
  • Chu S, McDonald T, Lin A et al. Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment. Blood 118(20), 5565–5572 (2011).
  • Graham S, Jorgenson H, Allan E et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to ST1571 in vitro. Blood 99(1), 319–325 (2002).
  • Corbin A, Agarwal A, Loriaux M et al. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J. Clin. Invest. 121(1), 396–409 (2011).
  • Hamilton A, Helgason GV, Schemionek M et al. Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood 119(6), 1501–1510 (2011).
  • 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 24(10), 1719–1724 (2010).
  • Hamad A, Sahli Z, El Sabban M, Mouteirik M, Nasr R. Emerging therapeutic strategies for targeting chronic myeloid leukemia stem cells. Stem Cells Int. 724360 (2013).
  • Sinclair A, Latif AL, Holyoake TL. Targeting survival pathways in chronic myeloid leukemia stem cells. Br. J. Pharmacol. 169(8), 1693–1707 (2013).
  • Konopleva M, Jordan C. Leukemic stem cells and microenvironment: biology and therapeutic targeting. J. Clin. Oncol. 29(5), 591–599 (2011).
  • Nwajei F, Konopleva M. The bone marrow microenvironment as niche retreats for hematopoietic and leukemic stem cells. Adv. Hematol. 953982 (2013).

Websites

  • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myelogenous Leukemia V.1.2014. © National Comprehensive Cancer Network, Inc 2013. All rights reserved. Accessed October 2013. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. www.nccn.org/professionals/physician_gls/pdf/cml.pdf
  • Surveillance Epidemiology and End Results. SEER Stat Fact Sheets: Chronic myeloid leukemia (2012). http://archive.is/zNIo (Accessed 9 November 2012)

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