Treatment of chronic myeloid leukemia in era of imatinib

Czech version

Authors: K. Indrák; E. Faber; M. Jarošová
Authors‘ workplace: Hemato-onkologická klinika Lékařské fakulty UP a FN Olomouc, přednosta prof. MUDr. Karel Indrák, DrSc.
Published in: Vnitř Lék 2009; 55(Suppl 1)(Supplementum 1): 65-73

Overview

Authors introduce their review with description of historic achievements that enabled to reach the actual stage of knowledge on ethiopathogenesis of chronic myeloid leukemia (CML), to synthetize first tyrosine kinase inhibitor – imatinib (Glivec, IM) and to develop the revolutionary targeted treatment of CML. Targeted therapy has both completely changed prognosis of patients with CML and stimulated further discoveries in ethiopathogenesis of other malignancies that was followed also by introduction of specific targeted treatment. Authors explain basic terms of cytogenetic and molecular evaluation of treatment results, determination of optimal therapeutic response and failure during targeted treatment of CML. They provide overview of imatinib failure management, experience with second generation tyrosine kinase inhibitors and review the actual role of allogeneic hematopoietic stem cell transplantation in CML. According to the recent recommendations for CML treatment issued by National Comprehensive Cancer Network (NCCN 1/2009) regular monitoring using highly sofisticated laboratory methods every 3 months is necessary. In case of failure monitoring should be even more frequent and possibility of participation in international trials may play an important role. Finaly, pitfalls of targeted treatment mainly treatment failure, intolerance and leukemic stem cell resistance to tyrosine kinase inhibitors are discussed. Continual research of mechanisms of resistance, development of new and reintroduction of „older“ drugs like interferon alpha provide substantial hope for the future CML management.

Key words:
chronic myeloid leukemia– Philadelphia chromosom– tyrosine kinase inhibitor– imatinib– dasatinib– nilotinib– cytogenetic response– molecular response– allogeneic hematopoietic stem cell transplantation

Sources

1. Nowell P, Hungerford D. A minute chromosome in human chronic granulocytic leukemia. Science 1960; 132: 1497.

2. Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290–293.

3. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990; 247: 824–830.

4. Goldman JM, Melo JV. Chronic myeloid leukemia – advances in biology a new approches to treatment. N Engl J Med 2003; 349: 1451–1464.

5. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 2000; 96: 3343–3356.

6. van Etten RA. Mechanism of transformation by the BCR-ABL oncogene: new perspectives in the post‑imatinib era. Leuk Res 2004; 28 (Suppl 1): 21–28.

7. Sawyers CL. Chronic myeloid leukemia. N Engl J Med 1999; 340: 1330–1340.

8. Schindler T, Bornmann W, Pellicena P et al. Structural mechanism for STI-571 inhibition of Abelson Tyrosine Kinase. Science 2000; 289: 1938–1942.

9. O’Brien SG, Guilhot F, Goldman JM et al. International Randomized Study of Interferon Versus STI571 (IRIS) 7-Year Follow‑up: Sustained Survival, Low Rate of Transformation and Increased Rate of Major Molecular Response (MMR) in Patients (pts) with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML‑CP) Treated with Imatinib (IM). ASH Annual Meeting 2008; 112. Abstract 186.

10. Faber E, Hluší A, Indrák K et al. Imatinib (Glivec®) v léčbě nemocných s akcelerovanou fází chronické myeloidní leukemie a Ph pozitivní akutní lymfoblastické leukemie. Trans Hemat dnes 2003; 9: 159–165.

11. Voglová J, Poznarová A, Chrobák L et al. Imatinib mesylát (Glivec®) v léčbě chronické fáze chronické myeloidní leukemie.Vnitř Lék 2004; 50: 21–29.

12. Baccarani M, Saglio G, Goldman J et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006; 108: 1809–1820.

13. Hochhaus A, Dreyling M. ESMO Guidelines Working Group. Chronic myelogenous leukemia: ESMO clinical recommendations for the diagnosis, treatment and follow‑up. Ann Oncol 2008; 19 (Suppl 2): i63–i64.

14. NCCN Clinical Practice Guidelines in Oncology TM: Chronic Myelogenous Leukemia. Updated Version V. I. 2009 (www.ncccn.org).

15. Klamová H, Voglová J. Diagnostické a léčebné postupy u chronické myeloidní leukemie dospělých v roce 2008. Trans Hemat dnes 2008; 14 (Suppl 1): 87–90.

16. Mahon FX, Huguet F, Guilhot F et al. Is it possible to stop imatinib in patients with chronic myeloid leukemia? An update from a french pilot study and first results from the multicentre “Stop imatinib” (STIM) study. Program and abstracts of the 50th american society of hematology annual meeting and exposition. ASH Annual Meeting 2008: 112: Abstract 187.

17. Hochhaus A, Muller MC, Radich J et al. Dasatinib‑associated major molecular responses are rapidly achieved in patients with chronic myeloid leukemia in chronic phase (CML‑CP) following resistance, suboptimal response or intolerance on imatinib. ASH Annual Meeting 2008; 112: Abstract 1095.

18. Baccarani M, Rosti G, Saglio G et al. Dasatinib time to and durability of major and complete cytogenetic response (MCyR and CCyR) in patients with chronic myeloid leukemia in chronic phase (CML‑CP). ASH Annual Meeting 2008; 112. Abstract 450.

19. Shah NP, Kantarjian HM, Kim DW et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib‑resistant and imatinib-intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 2008; 26: 3204–3212.

20. Shah NP, Kim DW, Kantarjian HM et al. Dasatinib dose‑optimization in chronic phase chronic myeloid leukemia (CML‑CP): two‑year data from CA180-034 show equivalent long term efficacy and improved safety with 100 mg once daily dose. ASH Annual Meeting) 2008; 112. Abstract 3225.

21. Muller MC, Cortes J, Kim DW et al. Dasatinib efficacy in patients with chronic myeloid leukemia in chronic phase (CML‑CP) and pre‑existing BCR-ABL mutations. ASH Annual Meeting 2008; 112. Abstract 449.

22. Kantarjian HM, Giles F, Bhalla KN et al. Nilotinib in chronic myeloid leukemia patients in vhronic phase (CML‑CP) with imatinib resistance or intolerance: 2-year rollow‑up results of a phase 2 study. ASH Annual Meeting 2008; 112. Abstract 3238.

23. Jabbour E, Kantarjian HM, Baccarani M et al. Minimal cross-intolerance between nilotinib and imatinib in patients with imatinib-intolerant chronic myeloid leukemia in chronic phase (CML‑CP) or accelerated phase (CML‑AP). ASH Annual Meeting 2008; 112. Abstract 3215.

24. Cortes J, O’Brien S, Borthakur G et al. Efficacy of dasatinib in patients with previously untreated chronic myelogenous leukemia (CML) in early chronic phase (CML‑CP). ASH Annual Meeting 2008; 112. Abstract 182.

25. Cortes J, O’Brien S, Jones D et al. Efficacy of nilotinib (formerly AMN107) in patients (pts) with newly diagnosed previously untreated philadelphia chromosome (Ph)-positive chronic myelogenous leukemia in early chronic phase (CML‑CP). ASH Annual Meeting 2008; 112. Abstract 446.

26. Rosti G, Castagnetti F, Poerio A et al. High and early rates of cytogenetic and molecular response with nilotinib 800 mg daily as first line treatment of ph-positive chronic myeloid leukemia in chronic phase of a phase 2 trial of the gimema CML working party. ASH Annual Meeting 2008; 112. Abstract 181.

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

28. Melo JV, Chuah C. Novel Agents in CML Therapy: Tyrosine Kinase Inhibitors and Beyond. Hematology Am Soc Hematol Edu Program 2008; 2008: 427–435.