Yazarlar : Hoy SM..

Yayın : Drugs.

Yayın Yılı : 2014

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/24807266

Konu : Lösemi

Literatür İçeriği :  Oral ponatinib (Iclusig^®) is a novel kinase inhibitor structurally designed with a carbon-carbon triple bond to accommodate the T315I mutation in the ABL kinase domain. It has demonstrated inhibitory activity against native BCR-ABL tyrosine kinase and a variety of BCR-ABL mutants, including T315I. Ponatinib is approved for the treatment of adults with T315I-positive chronic-, accelerated- or blast-phase chronic myeloid leukaemia (CML), or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) [in the EU and the USA], as well as those with chronic-, accelerated- or blast-phase CML, or Ph+ ALL who are resistant or intolerant to prior tyrosine kinase inhibitor therapy (EU) or for whom no other tyrosine kinase inhibitor therapy is indicated (USA). In a noncomparative, multinational, phase II study, therapy with ponatinib was associated with a major cytogenetic response within the first 12 months in over half of adults with chronic-phase CML and major haematological responses within the first 6 months in at least 50 % of adults with accelerated-phase CML and approximately 34 % of adults with blast-phase CML or Ph+ ALL after a median follow-up duration of 15, 16 and 6 months, respectively. Such benefits were observed regardless of whether the patients were resistant to dasatinib or nilotinib, or had the T315I mutation. Serious adverse reactions have been reported with ponatinib, with vascular occlusion, heart failure and hepatotoxicity prompting the US FDA to issue boxed warnings. Ponatinib is a valuable treatment option for adults with T315I-positive chronic-, accelerated- or blast-phase CML, or Ph+ ALL, as well as those with chronic-, accelerated- or blast-phase CML, or Ph+ ALL who are resistant or intolerant to prior tyrosine kinase inhibitor therapy, but before starting treatment, clinicians need to consider whether the potential benefits of therapy will outweigh the risks.

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