Ponatinib, tyrosinkinázový inhibitor třetí generace, v léčbě pacientů s chronickou myeloidní leukemií
| Title in English | Ponatinib, a third-generation tyrosine kinase inhibitor, in the treatment of patients with chronic myeloid leukaemia |
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| Authors | |
| Year of publication | 2015 |
| Type | Article in Periodical |
| Magazine / Source | Farmakoterapie |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | chronic myeloid leukaemia; tyrosine kinase inhibitors; ponatinib; T315I mutation; vascular adverse events |
| Description | Introduction of imatinib, a prototype of tyrosine kinase inhibitors (TKI) targeted therapy, into clinical practice substantially improved prognosis of patients with chronic myeloid leukemia (CML), especially if they are diagnosed in chronic phase. In fact, life expectancy for majority of chronic phase CML patients does not differ from that of the age-matched healthy population. However, in 25–30% of patients resistance to imatinib occurs, mainly due to Bcr-Abl kinase domain mutations. To evade resistance to imatinib, more efficient second-generation TKI were developed: dasatinib, nilotinib and bosutinib. Despite their undoubted efficacy, all available firstand second-generation TKI are ineffective against highly resistant T315I mutation. In order to overcome this mutation, ponatinib, a third-generation TKI was developed. Based on outstanding results of phase II trial, ponatinib was approved for the second line treatment of CML and Phpositive acute lymphoblastic leukaemia in United States (US) in December 2012, and for patients resistant or intolerant to dasatinib or nilotinib, or with T315I mutation in Europe in July 2013. Because of increasing evidence of serious vascular adverse events in ponatinib treated patients, ponatinib sales were temporarily suspended in US and phase II trial was interrupted. After narrowing of indication criteria and plenty of new safety measures adoption, ponatinib was returned into clinical practice as a requisite tool for optimal management of CML patients, especially if they harbour T315I mutation, or are resistant to second-generation TKI. |