Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second‐generation tyrosine kinase inhibitors in the real‐life practice: Identification of risk factors and the role of prophylaxis

Caocci, Giovanni; Mulas, Olga; Annunziata, Mario; Luciano, Luigiana; Bonifacio, Massimiliano; Orlandi, Ester; Pregno, Patrizia; Galimberti, Sara; Rossi, Antonella Russo; Abruzzese, Elisabetta; Iurlo, Alessandra; Martino, Bruno; Sgherza, Nicola; Binotto, Gianni; Castagnetti, Fausto; Gozzini, Antonella; Fozza, Claudio; Bocchia, Monica; Sicuranza, Anna; Stagno, Fabio; Efficace, Fabio; Usala, Emilio; Gregorio, F. De; Scaffidi, Luigi; Elena, Chiara; Pirillo, Francesca; Baratè, Claudia; Trawinska, Malgorzata Monika; Cattaneo, Daniele; Labate, Claudia; Gugliotta, Gabriele; Molica, Matteo; Specchia, Giorgina; Nasa, Giorgio La; Foà, Robin; Breccia, Massimo

doi:10.1002/ajh.25102

Cited by 27 publications

(19 citation statements)

References 7 publications

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“…AOEs represent off‐target relevant complications of TKIs, particularly second‐generation and third‐generation TKIs . Nilotinib and ponatinib interact with a considerable number of clinically relevant vascular targets implicated in endothelial cell survival and angiogenesis …”

Section: Discussionmentioning

confidence: 99%

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

Caocci

Mulas

Abruzzese

et al. 2019

Hematological Oncology

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Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 60‐month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28 months (range, 3‐69 months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P < 0.001). Patients aged ≥60 years showed a significantly higher incidence rate of AOEs (51.5% vs 16.9%, P = 0.008). In multivariate analysis, no association was found between AOEs and positive history of CV disease, age, dose of ponatinib, previous exposure to nilotinib, and comorbidities. Only the SCORE risk was confirmed as a significant predictive factor (P = 0.01; HR = 10.9; 95% C.I. = 1.7‐67.8). Patients aged ≥60 years who were treated with aspirin had a lower incidence rate of AOEs (33.3% vs 61.8%). Among the 14 reported AOEs, 78.6% of them showed grade 3 to 4 toxicity. This real‐life study confirmed the increased incidence of AOEs in CML patients treated with ponatinib, with high to very high SCORE risk. We suggest that patients aged ≥60 years who were treated with ponatinib should undergo prophylaxis with 100 mg/day of aspirin. Our findings emphasize personalized prevention strategies based on CV risk factors.

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Section: Discussionmentioning

confidence: 99%

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

Caocci

Mulas

Abruzzese

et al. 2019

Hematological Oncology

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“…In the prospective study by Caocci et al in 369 CML adult patients with the median age 50 years and median follow-up 4 years, who were stratifi ed according to the SCORE system, the patients with TCH > 5.17 mmol/l and LDL-CH > 1.8 mmol/l 3 months after treatment had a signifi cantly higher incidence of CVEs and high or very high SCORE risk maintained a signifi cant association with CVEs (25). The authors concluded that SCORE risk seemed to be useful to predict the development of atherosclerotic events in CML patients treated with nilotinib and should be calculated before the start of any TKIs (27).…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular events and atherogenic lipid profile in chronic myeloid leukemia patients treated with nilotinib versus imatinib

Petríková¹,

Slezakova²,

Sninska³

et al. 2021

BLL

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The aim of this study was to assess cardiotoxicity and potential adverse effects related to lipid metabolism during treatment with tyrosine kinase inhibitors (TKIs) imatinib and nilotinib in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: Eighty-two consecutive patients with CML, who received nilotinib and/or imatinib in a single haemato-oncological Slovak center between years 2002-2018 were evaluated in a retrospective study. The mean age was 55.8 years (range 22-77 years). Median of follow-up was 61.3 months. RESULTS: A signifi cantly higher incidence of dyslipidemia, signifi cantly higher levels of potential risk markers of cardiovascular disease small dense LDL cholesterol (sdLDL-CH) and a signifi cant increase in total cholesterol were found in the patients during treatment with nilotinib in comparison to imatinib. Dyslipidemia led to drug therapy in 22 % of the patients in the nilotinib group. Fourteen percent of the patients in the nilotinib group had one or more cardiovascular events, including peripheral artery disease (10 %), myocardial infarction (4 %) and stroke (4 %). CONCLUSION: A higher risk of cardiovascular events and atherogenic dyslipidemia were associated with nilotinib therapy. Patients treated with TKI, especially nilotinib, require an early modifi cation of cardiovascular risk factors and a careful cardiologic surveillance so that antileukemic therapy with this highly effective agent could continue (Tab. 4, Fig. 3, Ref. 32).

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“…The 10-year cardiovascular risk of CML patients can be assessed using the Systematic Coronary Risk Evaluation (SCORE) chart, Framingham score, or QRisk ® 3–2018 algorithm; thus, the precondition of atherosclerotic risk events in patients, before and during treatment with TKIs, should be evaluated [ 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Events throughout the Disease Course in Chronic Myeloid Leukaemia Patients Treated with Tyrosine Kinase Inhibitors—A Single-Centre Retrospective Study

Varga

Ţilea

Petra

et al. 2020

JCM

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Introduction. Cardiovascular risk factors, pre-existing comorbidities, molecular factors, and the direct effects of second- and third-generation BCR-ABL1 tyrosine kinase inhibitors on the vascular endothelium contribute to the progression of cardiovascular (CV) events, especially atherothrombotic conditions. The study objective was to evaluate comorbidities, the cardiovascular risk profile, and events throughout the chronic myeloid leukaemia disease course. Methods. Retrospective data from adults who experienced haematology treatment at a single centre were continuously updated and followed throughout the disease course. A total of 43 subjects conforming with the inclusion and exclusion criteria of the study protocol were finally recruited. The median disease course was 77.0 ± 17.5 months. Statistical analyses were performed. Results. More than three CV risk factors were identified in 41.9% of cases. Almost half of the cases had relevant comorbidities (Charlson Comorbidity Index (CCI) ≥ 4), and no statistically significant comorbidities were found when comparing the tyrosine kinase inhibitor (TKI) treatment subgroups (p = 0.53). The patients at high and very high CV risk, according to Systematic Coronary Risk Evaluation (SCORE) risk classification, had 75.0% CV events (12/22 patients), p = 0.45. Throughout the disease course, 19 cardiovascular events were reported in 37.2% patients (13 males/3 females, p < 0.03). Conclusion. To the best of our knowledge, this is the first study exploring cardiovascular risk factors in Romanian chronic myeloid leukaemia patients. This study reinforces the need for close long-term follow-up that should be performed by a multidisciplinary team. The target should be not only the disease and specific drug-related toxicities but, also, the identification of cardiovascular and metabolic risk factors before the commencement of and throughout TKI therapy.

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Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second‐generation tyrosine kinase inhibitors in the real‐life practice: Identification of risk factors and the role of prophylaxis

Cited by 27 publications

References 7 publications

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

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

Cardiovascular events and atherogenic lipid profile in chronic myeloid leukemia patients treated with nilotinib versus imatinib

Cardiovascular Events throughout the Disease Course in Chronic Myeloid Leukaemia Patients Treated with Tyrosine Kinase Inhibitors—A Single-Centre Retrospective Study

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