Ponatinib evaluation and safety in real-life chronic myelogenous leukemia patients failing more than two tyrosine kinase inhibitors: the PEARL observational study

Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real‐life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart

“…4 Other recent studies from real life reported a variable incidence rate of CVAEs from 23% to 56%, suggesting that male sex, previous history of AOEs, and previous exposure to nilotinib are considered risk factors. 5,6 Overall, these observations suggested the need to customize treatment approaches, considering the appropriate TKI selection according to baseline CV risk factors.…”

“…2 The incidence rate of AOEs following ponatinib treatment in real life was reported only in a few small patient cohorts followed up for short periods, showing variable outcomes. [3][4][5][6] Risk factors associated with the development of AOEs have been identified in basal CV risk factors and/or may include the following: a history of previous ischemic disease, 2 dose intensity and age at starting ponatinib, 7 male sex, previous history of AOEs, and previous exposure to nilotinib. 5 The usefulness of the Systematic Coronary Risk Evaluation (SCORE) risk assessment at disease baseline, a 10-year risk estimation of fatal CV disease based on sex, age, smoking, systolic pressure, and total cholesterol level, to identify patients with increased risk of occurrence of AOEs during ponatinib treatment has been suggested.…”

“…[3][4][5][6] Risk factors associated with the development of AOEs have been identified in basal CV risk factors and/or may include the following: a history of previous ischemic disease, 2 dose intensity and age at starting ponatinib, 7 male sex, previous history of AOEs, and previous exposure to nilotinib. 5 The usefulness of the Systematic Coronary Risk Evaluation (SCORE) risk assessment at disease baseline, a 10-year risk estimation of fatal CV disease based on sex, age, smoking, systolic pressure, and total cholesterol level, to identify patients with increased risk of occurrence of AOEs during ponatinib treatment has been suggested. 8,9 Given the growing interest on the occurrence of AOEs in CML patients as off-target effects in the long term and the emergence of a new interdisciplinary specialty of "cardio-oncology" focusing on the proper stratification of CV risk in CML patients and management of complications, ad hoc expert opinions in this field have been published.…”

Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management

“…Sixteen out of 49 patients (32.6%) obtained molecular response, almost all maintained it while on treatment despite dose reductions [15]. The French observational ponatinib evaluation and safety in real-life chronic myelogenous leukemia patients failing >2 TKIs PEARL study with 48 CP-CML patients similar to the PACE trial showed an OS rate of 80.5% at 3 years and a cumulative MMR of 81.8% at 18 months [16]. Real-world ponatinib prescribing data from the US showed that ponatinib is prescribed across all disease phases, therapy lines, and any mutational status.…”

Ponatinib and platelets a conflict in CML

“…7 In real life, this would mean a high percentage of patients with cardiovascular events. 8 Thus, what shall we do now for our patients? Physicians should optimize control of cardiovascular risk factors and carefully select patients when ponatinib therapy is considered.…”