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Contemporary treatment methods of adult patients with BCR/ABL1 positive chronic myeloid leukemia


Authors: Katarína Slezáková;  Martin Mistrík;  Angelika Bátorová
Authors‘ workplace: Klinika hematológie a transfuziológie LF UK, SZU a UN Bratislava, Slovenská republika
Published in: Vnitř Lék 2020; 66(4): 214-224
Category:

Overview

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia that is characterised by Philadelphia chromosome (Ph1 chromosome) and/or fusion gene BCR-ABL1 in bone marrow. Interpheron α and bone marrow transplantation used to be the main treatment modalities for patients with CML 20 years ago. Due to the introduction of imatinib mesylate since the year 2000 the outcome of CML patients has dramatically improved. The survival of both younger and elderly patients in the case of an optimal response has been prolonged and currently is close to survival of healthy population. Although, one third of patients does not respond well to first line imatinib and needs to change the treatment to second line tyrosine kinase inhibitors (TKI: bosutinib, dasatinib and nilotinib). Younger patients without cardiologic and metabolic disorders and those with poor risk profile score may have benefit from TKI of 2nd generation as a 1st line treatment option with the aim of reaching deeper molecular response and the chance of treatment free remission (TFR) in future. By older patients with severe comorbidities and in patients with good risk profile score imatinib as a 1st line treatment option can be used. For patients who are resistant simultaneously to 2nd generation TKI and for patients with mutation T315I ponatinib – TKI of 3rd generation can be used effectively. Intolerance and toxicity of TKI´s are the main barriers of effective CML treatment. TKI selection for each patient should be individual. Patient´s cooperation with medical team is crucial and inevitable in long time treatment process. The chance for TFR has become feasible for approximately 40–60 % CML patients in deep and durable molecular remission and represents a further important milestone in the management of CML patients.

Keywords:

remission – bosutinib – dasatinib – hematopoietic stem cell transplantation – chronic myeloid leukemia – imatinib – nilotinib – ponatinib – Tyrosine kinase inhibitors


Sources

1. O’Brien S, Berman E, Moore JO et al. NCCN Task Force report: tyrosine kinase inhibitor therapy selection in the management of patients with chronic myelogenous leukemia. J Natl Compr Cancer Netw 2011; 9: (Suppl. 2): S1–S25.

2. Hehlmann R, Hochhaus A, Baccarani M European Leukemia Net. Chronic myeloid leukaemia. Lancet 2007; 370: 342–350.

3. Bower H, Björkholm M, Dickman PW et al. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol 2016; 34: 2851–2857.

4. Sokal JE, Cox EB, Baccarani M et al. Prognostic discrimination in „good‑risk“ chronic granulocytic leukemia. Blood 1984; 63: 789–799.

5. Žáčková D Tyrozinkinázové inhibitory v léčbě starších pacientů s chronickou myeloidní leukémií - editorial. Vnitř Lék 2015; 61: 760–761.

6. Hochhaus A, Larson RA, Guilhot MD et al. Long‑Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med 2017; 376: 917–927.

7. Kantarjian H, Shah NP, Hochhaus A et al. Dasatinib versus imatinib in newly diagnosed chronic‑phase chronic myeloid leukkemia. N Engl J Med 2010; 362: 2260–2270.

8. Hehlmann R, Lauseker M, Saußele S et al. Assesment of imatinib as first‑line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non‑CML determinants. Leukemia 2017; 31: 2398–2406.

9. Kantarjian HM, Giles F, Bhalla K et al. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow‑up results. Blood 2011; 117: 1141–114.

10. Klamová H, Žižková H, Burda P et al. Současné trendy v léčbě a diagnostice chronické myeloidní leukemie. Transfuze Hematol dnes 2017; 23: (Suppl. 1): S34–S46.

11. Etienne G, Guilhot J, Rea D et al. Long‑Term Follow‑Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia. J Clin Oncol 2017; 35: 298–305.

12. Saussele S, Richter J, Gilhot J et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO‑SKI): a prespecified interim analysis of a prospective, multicentre, non‑randomised, trial. Lancet Oncol 2018; 19: 747–757.

13. Réa D, Nicolini FE, Tulliez M et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G‑TKI study. Blood 2017; 129: 846–854.

14. Baccarani M, Deininger MW, Rosti G et al. European LeukemiaNet Recommendations for the management of chronic myeloid leukemia 2013. Blood 2013; 122: 872–884.

15. Alhuraiji A, Kantarjian H, Boddu P et al. Prognostic significance of additional chromozomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors. Am J Hematol. 2018; 93: 84–90.

16. Radich JP, Deininger M, Abboud CN et al. Chronic Myeloid Leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Vanc Netw 2018; 16: 1108–1135.

17. Cohen MH, Williams G, Johnson G et al. Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res 2002; 8: 935–942.

18. Guilhot J, Baccarani M, Clark RE et al. Definitions, methodological and statictical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European Leukemia Net. Blood 2012; 119: 5963–5971.

19. Hehlman R, Berger U, Pfirrmann M et al. Drug treatment is superior to allografting as first‑line therapy in chronic myeloid leukemia. Blood 2007; 109: 4686–4692.

20. Gratwohl A, Pfirrmann M, Zander A et al. Long‑term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment. Leukemia 2016; 30: 562–569.

21. Westin JR, Kurzrock R It’s about time: lessons for solid tumors from chronic myelogenous leukemia therapy. Mol Cancer Ther 2012; 11: 2549–2555.

22. Mayer J, Klamová H, Žáčková D et al. Imatinib v první linii léčby nemocných s nově diagnotikovanou chronickou myeloidní leukemií v chronické fázi. Transfuze Hematol dnes 2008; 14: 150–158.

23. Hughes T, White D Which TKI? An embarrassment of riches for chronic myeloid leukemia patients. Hematology 2013; 2013: 168–175.

24. 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.

25. Breccia M, Cannella L, Frustraci A et al. Pleural‑pericardial effusion as uncommon complication in CML patients treated with Imatinib. Eur J Haematol 2005; 74: 89–90.

26. Hochhaus A, Baccarani M, Deininger M et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 2008; 22: 1200–1206.

27. Shah NP, Kim DW, Kantarjian H et al. 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 2010; 95: 232–240.

28. Cortes JE, Saglio G, Kantarjian HM et al. Final 5-year study results of DASISION: The dasatinib versus imatinib study in treatment‑naïve chronic myeloid patients trial. J Clin On‑ col 2016; 34: 2333–2340.

29. Breccia M, Stagno F, Luciano L et al. Dasatinib first‑line: Multicentric Italian experience outside clinical trials. Leuk Res 2016; 40: 24–29.

30. Shah NP, Rousselot P, Schiffer Ch et al. Dasatinib in imatinib‑resistant or intolerant chronic‑phase, chronic myeloid leukemia patients: 7-year follow‑up of study CA180-034. Am J Hematol 2016; 91: 869–874.

31. Saglio G, Kim DW, Issaragrisil S et al. Nilotinib verzus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010; 362: 2251–2259.

32. Saglio G, Hochhaus A, Hughes TP et al. ENESTnd Update: nilotinib (NIL) vs imatinib(IM) in patients (PTS) with newly diagnosed chronic myeloid leukemia in chronic phase (CML‑CP) and the impact of early molecular response (EMR) and Sokal risk at diagnosis on long‑term outcomes. Blood 2013; 122: abstract 92.

33. 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.

34. Hochhaus A, Saglio G, Larson RA et al. Nilotinib is associated with a reduced incidence of BCR‑ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood 2013; 121: 3703–3708.

35. Castagnetti F, Breccia M, Gugliotta G et al. Nilotinib 300 mg twice daily: an academic single‑arm study of newly diagnosed chronic phase chronic myeloid leukemia patients. Haematologica 2016; 101: 1200–1207.

36. Cortes JE, Kantarjian HM, Brümmendorf TH et al. Safety and efficacy of bosutinib (SKI606) in chronic phase Philadelphia chromosome‑positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 2011; 118: 4567–4576.

37. Cortes JE, Gambacorti‑Passerini C, Deininger MW et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol 2018; 36: 231–237.

38. Cortes JE, Khoudry HJ, Kantarjian HM et al. Long‑term bosutinib for chronic phase chronic myeloid keukemia after failure of imatinib plus dasatinib and/or nilotinib. Am J Hematol 2016; 91: 1206-1214.

39. O’Hare T, Shakespeare WC, Zhu X et al. AP24534, a pan‑BCR/ABL inhibitor for chronic myeloid leukemia, potently imhibits the T315I mutant and overcomes mutation‑based resistance. Cancer Cell 2009; 16: 401–412.

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Diabetology Endocrinology Internal medicine

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