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Incorporating Tyrosine Kinase Inhibitors into Treatment Regimens for AML and ALL: Is There a Right or Wrong Way?

  • Acute Leukemias (F Ravandi, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Although combination chemotherapy regimens have been clearly successful in treating a proportion of patients with acute leukemia, we are probably close to a ceiling of maximal benefit from such combinations. Identification of targets in the cellular signaling pathways and development of specific drugs against them have added to our armamentarium; our current challenge is how to best incorporate these agents into the currently available regimens.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Weinhouse S. National Cancer Act of 1971 – an editorial. Cancer Res. 1972;32(4):i–ii.

    CAS  PubMed  Google Scholar 

  2. Freireich EJ, Frei 3rd E, Holland JF, et al. Evaluation of a new chemotherapeutic agent in patients with 'advanced refractory' acute leukemia. Studies of 6-azauracil. Blood. 1960;16:1268–78.

    CAS  PubMed  Google Scholar 

  3. Frei 3rd E, Karon M, Levin RH, et al. The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood. 1965;26(5):642–56. Early study demonstrating the efficacy of combination therapy in childhood ALL.

    PubMed  Google Scholar 

  4. Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993;328(14):1002–6.

    Article  CAS  PubMed  Google Scholar 

  5. Ravandi F, Talpaz M, Estrov Z. Modulation of cellular signaling pathways: prospects for targeted therapy in hematological malignancies. Clin Cancer Res. 2003;9(2):535–50.

    CAS  PubMed  Google Scholar 

  6. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74. Important study clearly establishing the existence of recurring molecular events responsible for leukemogenesis and the availability of potential pathways for intervention.

    Article  Google Scholar 

  7. Pardoll D, Allison J. Cancer immunotherapy: breaking the barriers to harvest the crop. Nat Med. 2004;10(9):887–92.

    Article  CAS  PubMed  Google Scholar 

  8. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–7.

    Article  CAS  PubMed  Google Scholar 

  9. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344(14):1038–42.

    Article  CAS  PubMed  Google Scholar 

  10. Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542–51.

    Article  PubMed  Google Scholar 

  11. Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075–88.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Kantarjian H, O'Brien S, Cortes J, et al. Therapeutic advances in leukemia and myelodysplastic syndrome over the past 40 years. Cancer. 2008;113(7 Suppl):1933–52.

    Article  CAS  PubMed  Google Scholar 

  13. O'Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15(1):48–58.

    Article  PubMed  Google Scholar 

  14. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.

    Article  CAS  PubMed  Google Scholar 

  15. Ravandi F, Jorgensen JL, Thomas DA, et al. Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. Blood. 2013;122(7):1214–21.

    Article  CAS  PubMed  Google Scholar 

  16. Foa R, Vitale A, Vignetti M, et al. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011;118(25):6521–8.

    Article  CAS  PubMed  Google Scholar 

  17. Ottmann O, Dombret H, Martinelli G, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007;110(7):2309–15.

    Article  CAS  PubMed  Google Scholar 

  18. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783–96.

    Article  CAS  PubMed  Google Scholar 

  19. Wassmann B, Pfeifer H, Goekbuget N, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL). Blood. 2006;108(5):1469–77.

    Article  CAS  PubMed  Google Scholar 

  20. Levis M, Pham R, Smith BD, Small D. In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects. Blood. 2004;104(4):1145–50.

    Article  CAS  PubMed  Google Scholar 

  21. Stone RM, Fischer T, Paquette R, et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia. 2012;26(9):2061–8.

    Article  CAS  PubMed  Google Scholar 

  22. Schultz KR, Bowman WP, Aledo A, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin Oncol. 2009;27(31):5175–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Ravandi F, O'Brien S, Thomas D, et al. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010;116(12):2070–7.

    Article  CAS  PubMed  Google Scholar 

  24. Ravandi F, Cortes JE, Jones D, et al. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010;28(11):1856–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381–8.

    Article  CAS  PubMed  Google Scholar 

  26. Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19(18):3852–60.

    CAS  PubMed  Google Scholar 

  27. Ravandi F, Estey E, Jones D, et al. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009;27(4):504–10.

    Article  CAS  PubMed  Google Scholar 

  28. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111–21. Randomized trial demonstrating the superiority of a “chemo-free” regimen over chemotherapy in a specific acute leukemia.

    Article  CAS  PubMed  Google Scholar 

  29. Cortes JE, Kantarjian H, Foran JM, et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013;31(29):3681–7.

    Article  CAS  PubMed  Google Scholar 

  30. Ravandi F, Alattar ML, Grunwald MR, et al. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013;121(23):4655–62.

    Article  CAS  PubMed  Google Scholar 

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Conflict of Interest

Dr. Farhad Ravandi is a section editor for Current Hematologic Malignancy Reports. Dr. Ravandi has received research funding and honoraria from Bristol Myers Squibb, Celgene, Novartis, and Bayer/Onyx.

Human and Animal Rights and Informed Consent

This article does not report on any studies with human or animal subjects performed by the author.

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  1. MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    Farhad Ravandi

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  1. Farhad Ravandi
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Correspondence to Farhad Ravandi.

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Ravandi, F. Incorporating Tyrosine Kinase Inhibitors into Treatment Regimens for AML and ALL: Is There a Right or Wrong Way?. Curr Hematol Malig Rep 9, 144–147 (2014). https://doi.org/10.1007/s11899-014-0204-7

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  • DOI: https://doi.org/10.1007/s11899-014-0204-7

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