Ponatinib is a third generation kinase inhibitor designed to overcome the gatekeeper T315I mutation. In different trials this drug showed inhibitory activity against native BCR-ABL1 kinase and several ABL1 mutations. For this reason, ponatinib is currently indicated for the treatment of chronic myeloid leukaemia (CML) in every phase of disease resistant and/or intolerant to dasatinib and nilotinib and for whom imatinib is not indicated anymore or for patients with T315I mutation. The drug is also indicated for Ph+ acute lymphoblastic leukaemia (ALL). Ponatinib was temporarily suspended in 2013 for the occurrence of cardiovascular thrombotic events. Since then, different investigators analyzed baseline characteristics of patient candidates for ponatinib, especially cardiovascular profile, in order to describe general management recommendations in this setting. In this review, clinical trials data about the use of ponatinib in CML and Ph+ ALL patients will be discussed. It will be focused also about the safety and tolerability profile of the drug and future perspectives of employment.

Acute myeloid leukemia (AML), the most frequent acute leukemia in adults, has been historically treated with infusional cytarabine (ara-c) + daunorubicin (3 + 7) for at least 40 years. The first “target therapy” to be introduced was the monoclonal anti-CD33 gemtuzumab ozogamicin (GO) in 2004. Unfortunately, in 2010 it was voluntarily withdrawn from the market both for safety reasons related to potential liver toxicity and veno-occlusive disease (VOD) and because clinical studies failed to confirm the clinical benefit during induction and maintenance. Seven years later, GO was re-approved based on new data, including insights into its mechanism of action on its target receptor CD33 expressed on myeloid cells. The present review focuses on current biological information and clinical data from several studies investigating GO. Cytogenetic, molecular, and immunophenotypic data are now able to predict the potential positive advantages of GO, with the exception of high-risk AML patients who do not seem to benefit. GO can be considered a ‘repurposed drug’ that could be beneficial for some patients with AML, mostly in combination with new drugs already approved or currently in testing.

TP53is a key tumor suppressor gene with protean functions associated with preservation of genomic balance, including regulation of cellular senescence, apoptotic pathways, metabolism functions, and DNA repair. The vast majority ofde novoacute myeloid leukemia (AML) present unalteredTP53alleles. However,TP53mutations are frequently detected in AML related to an increased genomic instability, such as therapy‐related (t-AML) or AML with myelodysplasia-related changes. Of note,TP53mutations are associated with complex cytogenetic abnormalities, advanced age, chemoresistance, and poor outcomes. Recent breakthroughs in AML research and the development of targeted drugs directed at specific mutations have led to an explosion of novel treatments with different mechanisms. However, optimal treatment strategy for patients harboringTP53mutations remains a critical area of unmet need. In this review, we focus on the incidence and clinical significance ofTP53mutations inde novoand t-AML. The influence of these alterations on response and clinical outcomes as well as the current and future therapeutic perspectives for this hardly treatable setting are discussed.