Nilotinib for the treatment of chronic myeloid leukemia

Expert Review of Hematology

Volumn 1, Issue 1, 2008, Pages 29-39

  Kim, Theo Daniel ^a   Dörken, Bernd ^a   le Coutre, Philipp ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

BCR ABL; chronic myeloid leukemia; nilotinib; Philadelphia chromosome; resistance; tyrosine kinase inhibitor

Indexed keywords

4 METHYL N (3 (4 METHYLIMIDAZOL 1 YL) 5 (TRIFLUOROMETHYL)PHENYL) 3 ((4 PYRIDIN 3 YLPYRIMIDIN 2 YL)AMINO)BENZAMIDE; 4-METHYL-N-(3-(4-METHYLIMIDAZOL-1-YL)-5-(TRIFLUOROMETHYL)PHENYL)-3-((4-PYRIDIN-3-YLPYRIMIDIN-2-YL)AMINO)BENZAMIDE; ANTINEOPLASTIC AGENT; IMATINIB; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; PYRIMIDINE DERIVATIVE;

ARTICLE; CHEMISTRY; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL (TOPIC); DRUG ANTAGONISM; DRUG RESISTANCE; DRUG SCREENING; ECONOMICS; HUMAN; METABOLISM;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, NEOPLASM; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PYRIMIDINES;

EID: 77950670010     PISSN: 17474086     EISSN: 17474094     Source Type: Journal    
DOI: 10.1586/17474086.1.1.29     Document Type: Article

References (63)

1. Hehlmann R, Hochhaus A, Baccarani M. Chronic myeloid leukaemia. Lancet 370 (9584), 342–350 (2007).
2. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 96 (10), 3343–3356 (2000).
3. Druker BJ, Tamura S, Buchdunger E et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2 (5), 561–566 (1996).
4. Cohen MH, Johnson JR, Pazdur R. U.S. Food and Drug Administration Drug Approval Summary: conversion of imatinib mesylate (STI571; Gleevec) tablets from accelerated approval to full approval. Clin. Cancer Res. 11 (1), 12–19 (2005).
5. 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).
6. Hochhaus A, Druker BJ, Larson RA, O’Brien SG, Gathmann I, Guilhot F. IRIS 6-year follow-up: sustained survival and declining annual rate of transformation in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Presented at: American Society of Hematology Annual Meeting. Atlanta, GA, USA, 8–11 December 2007 (Abstract 25).
7. Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 8 (11), 1018–1029 (2007).
8. Gorre ME, Mohammed M, Ellwood K et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293 (5531), 876–880 (2001).
9. O’Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 110 (7), 2242–2249 (2007).
10. Shah NP, Nicoll JM, Nagar B et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2 (2), 117–125 (2002).
11. 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 108 (6), 1809–1820 (2006).
12. Sawyers CL, Hochhaus A, Feldman E et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a Phase II study. Blood 99 (10), 3530–3539 (2002).
13. Talpaz M, Silver RT, Druker BJ et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a Phase 2 study. Blood 99 (6), 1928–1937 (2002).
14. 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).
15. Branford S, Seymour JF, Grigg A et al. BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria. Clin. Cancer Res. 13 (23), 7080–7085 (2007).
16. Colombat M, Fort MP, Chollet C et al. Molecular remission in chronic myeloid leukemia patients with sustained complete cytogenetic remission after imatinib mesylate treatment. Haematologica 91 (2), 162–168 (2006).
17. Cortes J, O’Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response. Blood 104 (7), 2204–2205 (2004).
18. Rousselot P, Huguet F, Rea D et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 109 (1), 58–60 (2007).
19. Bhatia R, Holtz M, Niu N et al. Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood 101 (12), 4701–4707 (2003).
20. Graham SM, Jorgensen HG, Allan E et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 99 (1), 319–325 (2002).
21. Holtz MS, Slovak ML, Zhang F, Sawyers CL, Forman SJ, Bhatia R. Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation. Blood 99 (10), 3792–3800 (2002).
22. Deininger MW, O’Brien SG, Ford JM, Druker BJ. Practical management of patients with chronic myeloid leukemia receiving imatinib. J. Clin. Oncol. 21 (8), 1637–1647 (2003).
23. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305 (5682), 399–401 (2004).
24. Talpaz M, Shah NP, Kantarjian H et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 354 (24), 2531–2541 (2006).
25. Apperley JF. Part II: management of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 8 (12), 1116–1128 (2007).
26. Quintas-Cardama A, Kantarjian H, Cortes J. Flying under the radar: the new wave of BCR-ABL inhibitors. Nat. Rev. Drug Discov. 6 (10), 834–848 (2007).
27. Manley PW, Breitenstein W, Bruggen J et al. Urea derivatives of STI571 as inhibitors of Bcr-Abl and PDGFR kinases. Bioorg. Med. Chem. Lett. 14 (23), 5793–5797 (2004).
28. Weisberg E, Manley PW, Breitenstein W et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 7 (2), 129–141 (2005).
29. Golemovic M, Verstovsek S, Giles F et al. AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Clin. Cancer Res. 11 (13), 4941–4947 (2005).
30. O’Hare T, Walters DK, Stoffregen EP et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 65 (11), 4500–4505 (2005).
31. Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin JD. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br. J. Cancer 94 (12), 1765–1769 (2006).
32. Stover EH, Chen J, Lee BH et al. The small molecule tyrosine kinase inhibitor AMN107 inhibits TEL-PDGFRβ and FIP1L1-PDGFRα in vitro and in vivo. Blood 106 (9), 3206–3213 (2005).
33. Weisberg E, Wright RD, Jiang J et al. Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity. Gastroenterology 131 (6), 1734–1742 (2006).
34. von Bubnoff N, Gorantla SH, Kancha RK, Lordick F, Peschel C, Duyster J. The systemic mastocytosis-specific activating cKit mutation D816V can be inhibited by the tyrosine kinase inhibitor AMN107. Leukemia 19 (9), 1670–1671 (2005).
35. 14C]-AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl tyrosine kinase, in healthy subjects. Blood 106, (2005) (Abstract 4887).
36. + ALL). J. Clin. Oncol. 24 (18 Suppl.), (2006) (Abstract 3095).
37. Kantarjian H, Giles F, Wunderle L et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N. Engl. J. Med. 354 (24), 2542–2551 (2006).
38. Kantarjian HM, Giles F, Gattermann N et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood 110 (10), 3540–3546 (2007).
39. Kantarjian HM, Giles FJ, Bhalla KN et al. Nilotinib in chronic myelogenous leukemia in chronic phase (CML-CP) patients with imatinib-resistance or -intolerance: updated Phase 2 results. Haematologica 93 (Suppl. 1), (2008) (Abstract 0883).
40. le Coutre P, Ottmann OG, Giles F et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood 111 (4), 1834–1839 (2008).
41. le Coutre P, Giles FJ, Hochhaus A et al. Nilotinib in imatinib-resistant or -intolerant patients with chronic myelogenous leukemia in accelerated phase (CML-AP): update of a Phase 2 study. Haematologica 93 (Suppl. 1), Abstract 0118 (2008).
42. Giles FJ, Larson RA, Kantarjian HM et al. Nilotinib in chronic myelogenous leukemia in blast crisis (CML-BC) patients with imatinib-resistance or -intolerance: updated Phase 2 results. Haematologica 93 (Suppl. 1), Abstract 0117 (2008).
43. Abruzzese E, Alimena G, le Coutre P et al. Nilotinib in chronic myelogenous leukemia patients who failed prior imatinib and dasatinib therapy: updated results of an open-label Phase II study. J. Clin. Oncol. 26 (Suppl.), Abstract 7055 (2008).
44. Cortes JE, O’Brien SM, Ferrajoli A et al. Efficacy of nilotinib (AMN107) in patients (Pts) with newly diagnosed, previously untreated Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia in early chronic phase (CML-CP). J. Clin. Oncol. 26 (Suppl.), Abstract 7016 (2008).
45. Rosti G, Castagnetti F, Palandri F et al. Nilotinib 800 mg daily as first line treatment of chronic myeloid leukemia in early chronic phase: results of a Phase 2 trial of the GIMEMA CML Working Party. Haematologica 93 (Suppl. 1), Abstract 0404 (2008).
46. Singer JB, Shou Y, Giles F et al. UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. Leukemia 21 (11), 2311–2315 (2007).
47. + CML patients failing prior tyrosine kinase inhibitors (TKI) before starting nilotinib – analysis of data from compassionate use program. Haematologica 93 (Suppl. 1), Abstract 0557 (2008).
48. Hochhaus A, Kantarjian HM, Baccarani M et al. Minimal cross-intolerance between nilotinib and imatinib in patients with imatinib-intolerant chronic myelogenous leukemia (CML) in chronic phase (CP) or accelerated phase (AP). Haematologica 93 (Suppl. 1), Abstract 0141 (2008).
49. Kantarjian H, Sawyers C, Hochhaus A et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N. Engl. J. Med. 346 (9), 645–652 (2002).
50. Tam CS, Kantarjian H, Garcia-Manero G et al. Failure to achieve a major cytogenetic response by twelve months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia. Blood 112 (3), 516–518 (2008).
51. Bradeen HA, Eide CA, O’Hare T et al. Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. Blood 108 (7), 2332–2338 (2006).
52. Ray A, Cowan-Jacob SW, Manley PW, Mestan J, Griffin JD. Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study. Blood 109 (11), 5011–5015 (2007).
53. von Bubnoff N, Manley PW, Mestan J, Sanger J, Peschel C, Duyster J. Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107). Blood 108 (4), 1328–1333 (2006).
54. Willis SG, Lange T, Demehri S et al. High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood 106 (6), 2128–2137 (2005).
55. Jabbour E, Kantarjian H, Jones D et al. Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood 112 (1), 53–55 (2008).
56. + leukemias. Blood 109 (5), 2112–2120 (2007).
57. Shah NP, Skaggs BJ, Branford S et al. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J. Clin. Invest. 117 (9), 2562–2569 (2007).
58. + CML cells. Blood 109 (9), 4016–4019 (2007).
59. Konig H, Holtz M, Modi H et al. Enhanced BCR-ABL kinase inhibition does not result in increased inhibition of downstream signaling pathways or increased growth suppression in CML progenitors. Leukemia 22 (4), 748–755 (2008).
60. Copland M, Hamilton A, Elrick LJ et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 107 (11), 4532–4539 (2006).
61. Verstovsek S, Akin C, Manshouri T et al. Effects of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, on human mast cells bearing wild-type or mutated codon 816 c-kit. Leuk. Res. 30 (11), 1365–1370 (2006).
62. von Bubnoff N, Gorantla SP, Thone S, Peschel C, Duyster J. The FIP1L1-PDGFRA T674I mutation can be inhibited by the tyrosine kinase inhibitor AMN107 (nilotinib). Blood 107 (12), 4970–4971 (2006).
63. Hochhaus A, Druker B, Sawyers C et al. Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment. Blood 111 (3), 1039–1043 (2008).