open access

Vol 47, No 2 (2016)
Prace poglądowe / Reviews
Submitted: 2016-02-03
Published online: 2016-04-01
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Ponatinib in therapy of chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia

Tomasz Sacha
DOI: 10.1016/j.achaem.2016.04.002
·
Acta Haematol Pol 2016;47(2):128-138.

open access

Vol 47, No 2 (2016)
Prace poglądowe / Reviews
Submitted: 2016-02-03
Published online: 2016-04-01

Abstract

Ponatinib is a third generation tyrosine kinase inhibitor (TKI) active against wild type and mutant bcr/abl tyrosine kinase (including T315I). Ponatinib is approved for the treatment of adult patients with T315I mutation detected in CML (all phases) and in Ph+ ALL, for CML patients who are resistant to dasatinib or nilotinib and patients with Ph+ ALL who are intolerant or resistant to dasatinib and for whom subsequent imatinib treatment is not an optimal therapy. In phase II registration study (PACE), 267 patients with CML in chronic phase (CP), 83 in accelerated (AC) and 94 patients in blastic phase (BP) of CML or Ph+ALL were enrolled. T315I mutation was detected in 64, 18 and 46 patients, respectively. Two or more or three or more TKIs were used before ponatinib in 93% and 58% of patients, respectively for median period of 16.7 months. Major cytogenetic response (MCyR) by 12 months was achieved in 59% of CP CML patients (median follow-up 36 months), and major hematological response (MaHR) by 6 months in 55% of AC CML patients, and in 34% of BP CML and Ph+ALL patients (median follow-up 15.16 and 6 months, respectively). Efficacy of ponatinib as a first-line treatment for CP CML patients was shown in phase II and III trials. Serious adverse reactions have been reported with ponatinib, including vascular occlusion, heart failure and hepatotoxicity. Ponatinib is a valuable treatment option for patients with CML and Ph+ALL resistant or intolerant to previous therapy with TKIs and those with T315I mutation.

Abstract

Ponatinib is a third generation tyrosine kinase inhibitor (TKI) active against wild type and mutant bcr/abl tyrosine kinase (including T315I). Ponatinib is approved for the treatment of adult patients with T315I mutation detected in CML (all phases) and in Ph+ ALL, for CML patients who are resistant to dasatinib or nilotinib and patients with Ph+ ALL who are intolerant or resistant to dasatinib and for whom subsequent imatinib treatment is not an optimal therapy. In phase II registration study (PACE), 267 patients with CML in chronic phase (CP), 83 in accelerated (AC) and 94 patients in blastic phase (BP) of CML or Ph+ALL were enrolled. T315I mutation was detected in 64, 18 and 46 patients, respectively. Two or more or three or more TKIs were used before ponatinib in 93% and 58% of patients, respectively for median period of 16.7 months. Major cytogenetic response (MCyR) by 12 months was achieved in 59% of CP CML patients (median follow-up 36 months), and major hematological response (MaHR) by 6 months in 55% of AC CML patients, and in 34% of BP CML and Ph+ALL patients (median follow-up 15.16 and 6 months, respectively). Efficacy of ponatinib as a first-line treatment for CP CML patients was shown in phase II and III trials. Serious adverse reactions have been reported with ponatinib, including vascular occlusion, heart failure and hepatotoxicity. Ponatinib is a valuable treatment option for patients with CML and Ph+ALL resistant or intolerant to previous therapy with TKIs and those with T315I mutation.

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Keywords

Chronic myeloid leukemia; Acute lymphoblastic leukemia Ph+; T315I mutation; Ponatinib; Indications; Therapy

About this article
Title

Ponatinib in therapy of chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia

Journal

Acta Haematologica Polonica

Issue

Vol 47, No 2 (2016)

Pages

128-138

Published online

2016-04-01

Page views

181

Article views/downloads

517

DOI

10.1016/j.achaem.2016.04.002

Bibliographic record

Acta Haematol Pol 2016;47(2):128-138.

Keywords

Chronic myeloid leukemia
Acute lymphoblastic leukemia Ph+
T315I mutation
Ponatinib
Indications
Therapy

Authors

Tomasz Sacha

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