Seminars in Hematology
Volume 46 , Pages S16-S21 , April 2009

Practical Considerations for the Management of Patients in the Tyrosine Kinase Inhibitor Era

  • Michael O'Dwyer

      Affiliations

    • Department of Haematology, University Hospital Galway, National University of Ireland, Galway, Ireland
    • Corresponding Author InformationAddress correspondence to Michael O'Dwyer, MD, FRCPI, FRCPath, Professor of Haematology, University Hospital Galway, National University of Ireland, Galway, Ireland
    • ,
  • Ehab Atallah

      Affiliations

    • Division of Neoplastic Diseases and Related Disorders, Medical College of Wisconsin, Milwaukee, WI

References 

  1. National Comprehensive Cancer Network. NCCN: Clinical practice guidelines in oncology (Chronic myelogenous leukemia). 2009;2006 National Comprehensive Cancer Network, Inc. Version 2. Jenkintown, PA
  2. Hochhaus A, Drucker 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. Blood. 2007;110:15a–16a
  3. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645–652
  4. Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99:1928–1937
  5. Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG, 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. 2002;99:3530–3539
  6. Deininger MW, O'Brien SG, Ford JM, Druker BJ. Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol. 2003;21:1637–1647
  7. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, 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
  8. Guilhot F. Indications for imatinib mesylate therapy and clinical management. Oncologist. 2004;9:271–281
  9. Berman E, Nicolaides M, Maki RG, Fleisher M, Chanel S, Scheu K, et al. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med. 2006;354:2006–2013
  10. Fitter S, Dewar AL, Kostakis P, To LB, Hughes TP, Roberts MM, et al. Long-term imatinib therapy promotes bone formation in CML patients. Blood. 2008;111:2538–2547
  11. Jonsson S, Olsson B, Ohlsson C, Lorentzon M, Mellstrom D, Wadenvik H. Increased cortical bone mineralization in imatinib treated patients with chronic myelogenous leukemia. Haematologica. 2008;93:1101–1103
  12. Kantarjian HM, Larson RA, Guilhot F, O'Brian SG, Druker BJ. IRIS study group: Declining rates of adverse events (AEs), rare occurrence of serious AEs (SAEs), and no unexpected long-term side effects at 5 years in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) initially treated with imatinib (IM) in the International Randomized Study of Interferon vs STI571 (IRIS). Blood. 2006;108:2136
  13. Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354:2531–2541
  14. Goldman JM. How I treat chronic myeloid leukemia in the imatinib era. Blood. 2007;110:2828–2837
  15. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417
  16. Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004;47:6658–6661
  17. Weisberg E, Manley PW, Breitenstein W, Bruggen J, Cowan-Jacob SW, Ray A, et al. Characterization of AMN107, a selective inhibitor of native and mutant BCR-ABL. Cancer Cell. 2005;7:129–141
  18. Golemovic M, Verstovsek S, Giles F, Cortes J, Manshouri T, Manley PW, et al. AMN107, a novel aminopyrimidine inhibitor of BCR-ABL, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Clin Cancer Res. 2005;11:4941–4947
  19. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004;305:399–401
  20. Hochhaus A, Kantarjian H, Baccarani M, le Coutre P, Haque A, Gallagher N, et al. Minimal cross-intolerance between nilotinib and imatinib in patients with imatinib-intolerant chronic myelogenous leukaemia (CML) in chronic phase (CP) or accelerated phase (AP). Hematologica. 2008;93(Suppl 1):56–57
  21. Jabbour E, Hochhaus A, le Coutre P, Rosti G, Bhalla KN, Gallagher N, 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). J Clin Oncol. 2008;26:387s
  22. Guilhot F, Goldberg SL, Stone RM, Mauro M, Matloub Y, Chen TT, et al. Dasatinib lack of cross intolerance to imatinib in patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are intolerant to imatinib—a retrospective safety analysis. Haematologica. 2008;93(Suppl 1):51
  23. Khoury HJ, Goldberg SL, Mauro MJ, Stone RM, Matloub Y, Chen T, et al. Dasatinib lack of cross intolerance to imatinib in patients with chronic myelogenous leukemia chronic phase (CML-CP) intolerant to imatinib: A retrospective analysis of safety. J Clin Oncol. 2008;26:375s
  24. le Coutre P, Ottmann OG, Giles F, Kim DW, Cortes J, Gattermann N, 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. 2008;111:1834–1839
  25. le Coutre P, O'Dwyer M, Mendes W, Woodman R. The occurrence of pleural/pericardial effusions in Ph+ CML patients failing prior tyrosine kinase inhibitors (TKI) before starting nilotinib – analysis of data from compassionate use program Hematologica. 2008;93 Suppl 1:226.
  26. Cervantes F, Baccarani M, Lipton J, Matloub Y, Sinha R, Stone RM, et al. Dasatinib long-term efficacy in patients with chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to imatinib: a two-year update of the START-C study. Haematologica. 2008;93(Suppl 1):372
  27. Mauro MJ, Baccarani M, Cervantes F, Lipton JH, Matloub Y, Sinha R, et al. Dasatinib 2-year efficacy in patients with chronic-phase chronic myelogenous leukemia (CML-CP) with resistance or intolerance to imatinib (START-C). J Clin Oncol. 2008;26(Suppl):374s
  28. Hochhaus A, Druker B, Sawyers C, Guilhot F, Schiffer CA, Cortes J, 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-alpha treatment. Blood. 2008;111:1039–1043
  29. Novartis.CML Alliance. www.CMLalliance.com2008;
  30. Tsang J, Rudychev I, Pescatore SL. Prescription compliance and persistency in chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST) patients (pts) on imatinib (IM) [abstract 6119]. J Clin Oncol. 2006;24
  31. Cortes J, O'Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response. Blood. 2004;104:2204–2205
  32. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, 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. 2007;110:3540–3546
  33. Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007;109:2303–2309
  34. Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008;26:3204–3212

 Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals.

 STATEMENT OF CONFLICT OF INTEREST: Drs O'Dwyer and Atallah have received honoraria from Novartis Pharmaceuticals Corp.

PII: S0037-1963(09)00021-3

doi: 10.1053/j.seminhematol.2009.01.010

Seminars in Hematology
Volume 46 , Pages S16-S21 , April 2009

Article Tools

* Image Usage & Resolution