OBJECTIVES : The introduction of small molecule tyrosine kinase inhibitors (TKIs), such as ponatinib, opened new therapeutic possibilities for CML patients, dramatically increasing survival chances. Several recent publications have reported on ponatinib use and outcomes in CML patients treated in standard clinical practice (RW). The aim of this review is to describe ponatinib patient demographics, prescription patterns, effectiveness, and safety, given the impact of these parameters on survival, quality of life, and healthcare resource utilization.

METHODS : A systematic literature search was performed (01/2012-04/2019) in MEDLINE and Web of Science. PRISMA guidelines were followed as closely as possible. All publications including results on the outcomes (safety and/or effectiveness) of ponatinib use in patients that had not been enrolled in clinical trials were included. Sensitivity analyses to estimate the impact of study inclusion/exclusion on the calculated proportion of patients receiving a given starting dose were performed.

RESULTS : 25 publications (9 manuscripts and 16 abstracts) were selected. Ponatinib starting dose was calculated to be 45 mg/d in 54% and 30 or 15 mg/d in 46% of CML patients. Dose reduction of ponatinib was reported in 8 studies (in 5 of these after achieving patient response, to minimize toxicity). No relationship was identified between patient response and starting dose, age, or number of previous TKI treatments. 3 studies reported occurrence of serious or fatal cardiovascular CV events in high CV risk patients. Studies where more than half of patients were started with a reduced dose (5) and/or the median age was under 45 (3) reported lower incidence of serious CV events.

CONCLUSIONS : Published RW studies suggest a positive impact of ponatinib dose management in reducing severe CV events, while still achieving response to treatment, however their heterogeneity, limited number, and small enrolled populations prevent the disentanglement of the effect of potential confounders and effect modifiers.