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Traitement par inhibiteurs de tyrosine-kinase de 2e génération chez les patients en échec de l’imatinib

Treatment by second-generation tyrosine-kinase inhibitors in patients with imatinib failure

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Oncologie

Abstract

Imatinib (IM) has dramatically improved the prognosis of chronic myeloid leukemia patients. Unfortunately, 30% of the patients will have to discontinue IM first-line treatment because of failure or intolerance. Second-generation tyrosine-kinase inhibitors, for example nilotinib, dasatinib, and the not yet licensed bosutinib, have been evaluated in phase II clinical trials in this setting. With a median follow-up of at least 24months, most of the responses are sustained while the safety profile of the three drugs appears acceptable but clearly different between the drugs. This review focuses on the available data regarding the efficacy and the safety profile of the three drugs.

Résumé

L’imatinib a transformé le pronostic des patients atteints de leucémie myéloïde chronique. Néanmoins, 30 % des patients vont interrompre le traitement du fait d’une résistance ou d’une intolérance au traitement. Les inhibiteurs de tyrosine-kinase de deuxiéme génération (ITK2G) [nilotinib, dasatinib et bosutinib] ont été évalués dans cette double indication. Avec un suivi médian de plus de 24 mois, la plupart des réponses obtenues apparaissent durables, pour un profil de tolérance acceptable mais différent entre les trois molécules. Cette revue fait le point sur les données actuellement disponibles concernant l’efficacité et le profil de tolérance des trois molécules.

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Références

  1. Aichberger KJ, Herndlhofer S, Schernthaner GH, et al. (2011) Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. Am J Hematol 86: 533–539

    Article  PubMed  CAS  Google Scholar 

  2. Apperley JF, Cortes JE, Kim DW, et al. (2009) Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial. J Clin Oncol 27: 3472–3479

    Article  PubMed  CAS  Google Scholar 

  3. Baccarani M, Cortes J, Pane F, et al. (2009) Chronic myeloid leukemia: an update of concepts and management recommendations of European Leukemia-Net. J Clin Oncol 27: 6041–6051

    Article  PubMed  CAS  Google Scholar 

  4. Corbin AS, La RP, Stoffregen EP, et al. (2003) Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 101: 4611–4614

    Article  PubMed  CAS  Google Scholar 

  5. Cortes JE, Kantarjian HM, Brummendorf TH, et al. (2011) 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: 4567–4576

    Article  PubMed  CAS  Google Scholar 

  6. Gambacorti-Passerini C, Antolini L, Mahon FX, et al. (2011) Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst 103: 553–561

    Article  PubMed  CAS  Google Scholar 

  7. Giles FJ, Kantarjian HM, le Coutre PD, et al. (2012) Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase. Leukemia 26(5):959–962

    Article  PubMed  CAS  Google Scholar 

  8. Hochhaus A, O’Brien SG, Guilhot F, et al. (2009) Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 23: 1054–1061

    Article  PubMed  CAS  Google Scholar 

  9. Hughes T, Saglio G, Branford S, et al. (2009) Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol 27: 4204–4210

    Article  PubMed  CAS  Google Scholar 

  10. Kantarjian H, O’Brien S, Jabbour E, et al. (2012) Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood 119: 1981–1987

    Article  PubMed  CAS  Google Scholar 

  11. Kantarjian HM, Giles FJ, Bhalla KN, et al. (2011) Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood 117: 1141–1145

    Article  PubMed  CAS  Google Scholar 

  12. Kim DH, Kamel-Reid S, Chang H, et al. (2009) Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia. Haematologica 94: 135–139

    Article  PubMed  CAS  Google Scholar 

  13. Kreutzman A, Juvonen V, Kairisto V, et al. (2010) Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood 116: 772–782

    Article  PubMed  CAS  Google Scholar 

  14. le Coutre PD, Giles FJ, Hochhaus A, et al. (2012) Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. Leukemia 26(6):1189–1194

    Article  PubMed  Google Scholar 

  15. le Coutre PD, Turkina A, Kim DW, et al. (2009) Efficacy and safety of nilotinib in elderly patients with imatinib-resistant or -intolerant chronic myeloid leukemia (CML) in chronic phase (CP): a Sub-Analysis of the ENACT (Expanding Nilotinib Access in Clinical Trials) Study. ASH Annual Meeting Abstracts 114: 3286

    Google Scholar 

  16. le Coutre P, Rea D, Abruzzese E, et al. (2011) Severe peripheral arterial disease during nilotinib therapy. J Natl Cancer Inst 103: 1347–1348

    Article  PubMed  Google Scholar 

  17. Lipton JH, le Coutre PD, Wang J, et al. (2008) Nilotinib in elderly chronic myeloid leukemia patients in chronic phase (CMLCP) with imatinib resistance or intolerance: efficacy and safety analysis. ASH Annual Meeting Abstracts 112: 3233

    Google Scholar 

  18. Milojkovic D, Nicholson E, Apperley JF, et al. (2010) Early prediction of success or failure of treatment with secondgeneration tyrosine-kinase inhibitors in patients with chronic myeloid leukemia. Haematologica 95: 224–231

    Article  PubMed  CAS  Google Scholar 

  19. Montani D, Bergot E, Gunther S, et al. (2012) Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 125: 2128–2137

    Article  PubMed  CAS  Google Scholar 

  20. Mustjoki S, Ekblom M, Arstila TP, et al. (2009) Clonal expansion of T/NK-cells during tyrosine-kinase inhibitor dasatinib therapy. Leukemia 23: 1398–405

    Article  PubMed  CAS  Google Scholar 

  21. Nicolini FE, Masszi T, Shen Z, et al. (2012) Expanding Nilotinib Access in Clinical Trials (ENACT), an open-label multicenter study of oral nilotinib in adult patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase or blast crisis. Leuk Lymphoma 53: 907–914

    Article  PubMed  CAS  Google Scholar 

  22. Nicolini FE, Turkina A, Shen ZX, et al. (2012) Expanding Nilotinib Access in Clinical Trials (ENACT): an open-label, multicenter study of oral nilotinib in adult patients with imatinib-resistant or imatinib-intolerant Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. Cancer 118: 118–126

    Article  PubMed  CAS  Google Scholar 

  23. Porkka K, Khoury HJ, Paquette RL, et al. (2010) Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer 116: 377–386

    Article  PubMed  CAS  Google Scholar 

  24. Quintas-Cardama A, Kantarjian H, O’Brien S, et al. (2007) Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol 25: 3908–3914

    Article  PubMed  CAS  Google Scholar 

  25. Saglio G, Hochhaus A, Goh YT, et al. (2010) Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of followup in a phase 3 study: efficacy and tolerability of 140 mg once daily and 70 mg twice daily. Cancer 116: 3852–3861

    Article  PubMed  CAS  Google Scholar 

  26. Shah NP, Kim DW, Kantarjian H, et al. (2010) Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica 95: 232–240

    Article  PubMed  CAS  Google Scholar 

  27. Soverini S, Hochhaus A, Nicolini FE, et al. (2011) BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine-kinase inhibitors: recommendations from an expert panel on behalf of European Leukemia-Net. Blood 118: 1208–1215

    Article  PubMed  CAS  Google Scholar 

  28. Weisberg E, Manley PW, Breitenstein W, et al. (2005) Characterization of AMN107, a selective inhibitor of native and mutant BCR-ABL. Cancer Cell 7: 129–141

    Article  PubMed  CAS  Google Scholar 

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Correspondence to G. Etienne.

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Etienne, G. Traitement par inhibiteurs de tyrosine-kinase de 2e génération chez les patients en échec de l’imatinib. Oncologie 14, 589–595 (2012). https://doi.org/10.1007/s10269-012-2214-1

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  • DOI: https://doi.org/10.1007/s10269-012-2214-1

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