Advertisement

Der Onkologe

, Volume 24, Issue 5, pp 427–442 | Cite as

Chronische myeloische Leukämie

  • Thomas ErnstEmail author
  • Ellen Obstfelder
  • Andreas Hochhaus
CME
  • 490 Downloads

Zusammenfassung

Die Einführung des Tyrosinkinaseinhibitors (TKI) Imatinib verbesserte die Prognose bei chronischer myeloischer Leukämie (CML) erheblich. Mit den Zweitgenerationsinhibitoren Nilotinib, Dasatinib und Bosutinib werden im Vergleich zu Imatinib raschere und tiefere molekulare Remissionen mit verändertem Nebenwirkungsprofil erzielt. Lang andauernde, behandlungsfreie Remissionen bei einer steigenden Zahl von Patienten verstärken die Hoffnung auf eine Heilbarkeit der CML. Entscheidend ist ein konsequentes zytogenetisches und molekulares Follow-up der CML-Patienten mit standardisierten Methoden, um den Remissionsstatus regelmäßig zu überprüfen. Der Einsatz von Interferon-α parallel zu oder nach einer TKI-Therapie geht mit der Induktion einer Immunantwort gegen den leukämischen Klon einher, was die Remissionsrate weiter erhöht. Ein neuer allosterischer Kinaseinhibitor (Asciminib) könnte die CML-Therapie künftig weiter verbessern.

Schlüsselwörter

Myeloproliferative Neoplasien Tyrosinkinaseinhibitor Minimale Resterkrankung BCR-ABL Molekulares Monitoring 

Chronic myeloid leukemia

Abstract

The advent of tyrosine kinase inhibitors (TKI) imatinib has considerably improved prognosis of patients with chronic myeloid leukemia (CML). In comparison to imatinib, first-line use of second-generation inhibitors nilotinib, dasatinib, and bosutinib has led to faster and deeper molecular remissions accompanied by a novel adverse event profile. Long-lasting treatment-free remission in an important minority of patients prompted the hope for curability of CML. An essential part of the management of CML patients is consequent cytogenetic and molecular follow-up with standardized methods to regularly assess the remission status. The use of interferon-α in parallel with or after TKI therapy is associated with the induction of an immune response against the leukemic clone with further improvement of the remission rate. A novel allosteric kinase inhibitor (asciminib) could further improve treatment of CML patients in the near future.

Keywords

Myeloproliferative neoplasms Tyrosinkinase inhibitor  Minimal residual disease Molecular monitoring 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

A. Hochhaus erhielt Forschungsunterstützung von den Firmen Novartis, BMS, Ariad, Pfizer und MSD. T. Ernst und E. Obstfelder geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Hehlmann R et al (2007) Chronic myeloid leukaemia. Lancet 370:342–350CrossRefPubMedGoogle Scholar
  2. 2.
    Arber DA et al (2016r) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405CrossRefPubMedGoogle Scholar
  3. 3.
    Baccarani M et al (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122:872–884CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pfirrmann M et al (2016) Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia 30(1):48–56CrossRefPubMedGoogle Scholar
  5. 5.
    Hochhaus A et al (2017) Long-term outcomes of imatinib treatment for CML. N Engl J Med 376(10):917–927CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Eskazan AE et al (2017) Outcomes of chronic myeloid leukemia patients with early molecular response at 3 and 6 months: a comparative analysis of generic imatinib and glivec. Clin Lymphoma Myeloma Leuk 17(12):804–811CrossRefPubMedGoogle Scholar
  7. 7.
    Weisberg E et al (2007) Second generation inhibitors of bcr-abl for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 7:345–356CrossRefPubMedGoogle Scholar
  8. 8.
    Hochhaus A et al (2016) Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5‑year update of the randomized ENESTnd trial. Leukemia 30:1044–1054CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cortes JE et al (2016) Final 5‑year study results of DASISION: the dasatinib versus Imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol 34:2333–2340CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    La Rosée P et al (2013) Improved tolerability by a modified intermittent treatment schedule of dasatinib for patients with chronic myeloid leukemia resistant or intolerant to imatinib. Ann Hematol 92:1345–1350CrossRefPubMedGoogle Scholar
  11. 11.
    Cortes JE et al (2018) Bosutinib versus imatinib for newly diagnosed CML: results from the randomized BFORE trial. J Clin Oncol 36(3):231–237CrossRefPubMedGoogle Scholar
  12. 12.
    Preudhomme C (2010) Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 363:2511–2521CrossRefPubMedGoogle Scholar
  13. 13.
    Simonsson B et al (2011) Combination of pegylated IFN-alpha2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood 118:3228–3235CrossRefPubMedGoogle Scholar
  14. 14.
    Burchert A et al (2010) Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia. J Clin Oncol 28:1429–1435CrossRefPubMedGoogle Scholar
  15. 15.
    Burchert A et al (2015) Interferon alpha 2 maintenance therapy may enable high rates of treatment discontinuation in chronic myeloid leukemia. Leukemia 29:1331–1335CrossRefPubMedGoogle Scholar
  16. 16.
    Mahon FX et al (2010) 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 11:1029–1035CrossRefPubMedGoogle Scholar
  17. 17.
    Saussele S et al. (2018) Discontinuation of treatment in chronic myeloid leukemia – prospective analysis of molecular recurrence-free survival in the EURO-SKI trial. Lancet Oncol (im Druck)Google Scholar
  18. 18.
    Schmidt M et al (2014) Molecular defined clonal evolution in patients with chronic myeloid leukemia independent of the BCR-ABL status. Leukemia 28(12):2292–2299CrossRefPubMedGoogle Scholar
  19. 19.
    Kantarjian HM 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 117:1141–1145CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    le Coutre PD 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 26:1189–1194CrossRefPubMedGoogle Scholar
  21. 21.
    Giles FJ et al (2012) Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase. Leukemia 26:959–962CrossRefPubMedGoogle Scholar
  22. 22.
    Hochhaus A et al (2008) Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 22:1200–1206CrossRefPubMedGoogle Scholar
  23. 23.
    Apperley JF et al (2009) Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START A trial. J Clin Oncol 27:3472–3479CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cortes J et al (2007) Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 109:3207–3213CrossRefPubMedGoogle Scholar
  25. 25.
    Hughes T 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 27:4204–4210CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Müller MC et al (2009) Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting bcr-abl mutations. Blood 114:4944–4953CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Cortes JE et al (2013) A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med 369:1783–1796CrossRefPubMedGoogle Scholar
  28. 28.
    Lipton JH et al (2016) Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol 17:612–621CrossRefPubMedGoogle Scholar
  29. 29.
    Saussele S et al (2010) 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 115:1880–1885CrossRefPubMedGoogle Scholar
  30. 30.
    Hehlmann R (2012) How I treat CML blast crisis. Blood 120:737–747CrossRefPubMedGoogle Scholar
  31. 31.
    Cross NC et al (2012) Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia 26:2172–2175CrossRefPubMedGoogle Scholar
  32. 32.
    Hanfstein B et al (2012) Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 26:2096–2102CrossRefPubMedGoogle Scholar
  33. 33.
    Hanfstein B et al (2014) Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib. Leukemia 28:1988–1992CrossRefPubMedGoogle Scholar
  34. 34.
    Hochhaus A, La Rosée P (2004) Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia 18:1321–1331CrossRefPubMedGoogle Scholar
  35. 35.
    Soverini S 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 LeukemiaNet. Blood 118:1208–1215CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • Thomas Ernst
    • 1
    Email author
  • Ellen Obstfelder
    • 1
  • Andreas Hochhaus
    • 1
  1. 1.Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin IIUniversitätsklinikum JenaJenaDeutschland

Personalised recommendations