Healthcare professionals are advised that there is a risk of posterior reversible encephalopathy syndrome (PRES, also known as reversible posterior leukoencephalopathy syndrome) in patients taking ponatinib. A routine European review suggests that the risk could be up to 1 in 100 people who are taking the medicine. Treatment should be interrupted if PRES is confirmed, and resumed only when it has resolved and if the benefits of continuing treatment outweigh the risk of PRES.
PRES is a neurological disorder that can present with seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances.
The advice comes from the UK Medicines and Healthcare products Regulatory Agency following a European post-marketing review of ponatinib that identified five cases of PRES; two cases improved after treatment withdrawal, and did not reappear when restarted at a lower dose. The UK Summary of Product Characteristics lists PRES as an uncommon undesirable effect (that could affect up to 1 in 100 people).
Ponatinib (a tyrosine kinase inhibitor) is indicated for adults with chronic phase, accelerated phase, or blast phase chronic myelogenous leukaemia who are resistant or unsuitable for treatment with other tyrosine kinase inhibitors, or who have the T315I mutation.
Patients receiving ponatinib should be advised to contact their healthcare professional immediately if they develop sudden-onset severe headache, confusion, seizures, or vision changes.See Management: approach See Management: treatment algorithm
Malignant clonal disorder of haematopoietic stem cells.
At presentation, one third of patients may be asymptomatic; if present, symptoms typically include malaise, fever, weight loss, abdominal discomfort, and night sweats.
Splenomegaly is the most common physical finding; nearly all patients will have elevated WBC count.
Presence of Philadelphia chromosome and /or molecular demonstration of the BCR-ABL transcript confirms diagnosis.
Treatment with a BCR-ABL tyrosine kinase inhibitor gives long-term remission without significant adverse events in most patients.
Chronic myelogenous leukaemia (CML) is a malignant clonal disorder of the haematopoietic stem cell that results in marked myeloid hyperplasia of the bone marrow.  Dysregulation of haematopoiesis arises due to a BCR-ABL fusion gene that causes an abnormal expansion of myeloid cells in the bone marrow and peripheral blood. The 'chronic phase' of the disease may transform to an 'accelerated' or 'blast' phase in 5% to 10% of patients despite treatment with a tyrosine kinase inhibitor, the latter resulting in acute myeloid or acute lymphoblastic leukaemia.  
Honorary Consultant in Haematology
The Christie NHS Foundation Trust
TS has received travel support and speaker expenses from Novartis, and has served as a consultant to Novartis for development of drugs for indications other than CML.
Dr Tim Somervaille would like to gratefully acknowledge Dr Han Myint and Dr Robert Chen, the previous contributors to this monograph. HM sits on the advisory board of Novartis and Bristol-Myers Squibb, and also does speaking engagements on their behalf. RC declares that he has no competing interests.
Section of Hematology and Oncology
Department of Internal Medicine
Wake Forest University Baptist Medical Center
RC declares that she has no competing interests.
Professor of Haematology
Royal Liverpool University Hospital
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