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Tyrosine kinase inhibitors in Ph+ acute lymphoblastic leukaemia: facts and perspectives

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Abstract

Two tyrosine kinase inhibitors (TKIs), imatinib and dasatinib, are registered for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) in adults. Other two TKIs (nilotinib and ponatinib) have been tested in the second-line, can offer an alternative in the patients who fail the first-line, and can acquire a role also in the first-line. Here, we provide a summary of the reports of TKIs, used alone, and in combination with chemotherapy. TKIs are very effective alone and with corticosteroids and are likely to improve substantially the outcome when they are combined with standard or dose-adapted chemotherapy. While the complete haematologic remission rate is always very high, close to 100 %, the cytogenetic and molecular remission rates are lower, so that TKIs are still considered as a complement to chemotherapy and as a bridge to allogeneic stem cell transplantation (allo-SCT). However, many patients relapse before transplant, and many patients still relapse, even if they have been submitted to allo-SCT. A proper use of TKIs, the introduction of ponatinib, and of “new generation” TKIs should improve further on the outcome of Ph+ ALL.

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Authors and Affiliations

  1. Unit of Blood Diseases and Stem Cell Transplantation, AO Spedali Civili di Brescia, Brescia, Italy

    Michele Malagola

  2. Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy

    Michele Malagola

  3. Department of Specialistic, Diagnostic and Experimental Medicine, S.Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy

    Cristina Papayannidis

  4. Department of Hematology/Oncology “L. and A. Seràgnoli”, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy

    Michele Baccarani

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  1. Michele Malagola
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Michele Baccarani received honoraria from Novartis, Bristol-Myers Squibb, Pfizer, and Ariad and serves on the speaker’s bureau of Novartis and Bristol Myers-Squibb. All the other authors have nothing to disclose. This paper represents original work and has not been previously published or simultaneously submitted elsewhere. This manuscript has been written, read, and approved by all the authors.

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Malagola, M., Papayannidis, C. & Baccarani, M. Tyrosine kinase inhibitors in Ph+ acute lymphoblastic leukaemia: facts and perspectives. Ann Hematol 95, 681–693 (2016). https://doi.org/10.1007/s00277-016-2617-y

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