Cardiovascular Risk and Cardiovascular Events in Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors

Assunção, Paola Morelato; Lana, Tamires Prates; Delamain, Márcia Torresan; Duarte, Graciana Alves; Zulli, Roberto; Lorand-Metze, Irene; Souza, Cármino Antônio de; Paula, Erich Vinícius De; Pagnano, Kátia Bórgia Barbosa

doi:10.1016/j.clml.2018.12.004

Cited by 16 publications

(10 citation statements)

References 29 publications

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“…As expected, patients with preexisting cardiovascular risk factors have a higher risk of developing CV-AEs and AT-AEs, irrespective of the specific TKI used. 35,36 The IR of CV-AEs and AT-AEs was highest in the early years of TKI therapy and varied among TKIs. Overall, ponatinib therapy is associated with the highest risk of CV-AEs and AT-AEs.…”

Section: Discussionmentioning

confidence: 99%

Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

Jain¹,

Kantarjian²,

Boddu³

et al. 2019

Blood Advances

104

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Cardiovascular or arteriothrombotic adverse events (CV- or AT-AEs) are reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). The incidence and characteristics across different TKI have not been systematically analyzed. We analyzed 531 patients treated with frontline TKIs in different prospective trials: imatinib 400 mg (n = 71) and 800 mg (n = 203), nilotinib (n = 108), dasatinib (n = 106), and ponatinib (n = 43). Characteristics and incidence of new-onset CV-AEs and AT-AEs were analyzed. Poisson regression models assessed factors associated with AE incidence. Median follow-up was 94 months (range, 2-195). Overall, 237 patients (45%) developed CV-AEs and 46 (9%) developed AT-AEs. Hypertension was the most common AE seen in 175 patients (33%; grade 3/4 in 17%). CV-AE and AT-AE incidence ratios (IRs) with 95% confidence intervals (CIs) were 8.6 (7.6-9.8) and 1.7 (1.2-2.2) per 100 person-years. Among the TKIs, ponatinib showed the highest IR (95% CI) for CV-AEs and AT-AEs at 40.7 (27.9-59.4) and 9.0 (4.1-20.1). In multivariate analysis, ponatinib therapy was associated with increased incidence rate ratio (IRR) for CV-AEs (4.62; 95% CI, 2.7-7.7; P < .0001) and AT-AEs (6.38; 95% CI, 1.8-21.8; P < .0001) compared with imatinib 400. In summary, there is an increased risk of CV-AEs (except hypertension) and AT-AEs in CML patients treated with newer TKIs, particularly with ponatinib. Patients on TKIs must be informed and closely monitored for vascular AEs. These studies were registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, #NCT00050531, #NCT00254423, #NCT00129740, and #NCT01570868.

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Section: Discussionmentioning

confidence: 99%

Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

Jain¹,

Kantarjian²,

Boddu³

et al. 2019

Blood Advances

104

View full text Add to dashboard Cite

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“…Nilotinib is associated with an increased risk of peripheral arterial occlusive disease (PAOD). [92][93][94][95][96] Patients should be evaluated for preexisting PAOD and vascular risk factors before starting and during treatment with nilotinib. If PAOD is confirmed, nilotinib should be permanently discontinued.…”

Section: Nilotinibmentioning

confidence: 99%

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Deininger

Shah

Altman³

et al. 2020

Journal of the National Comprehensive Cancer Network

193

210

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Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

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“…Arterial hypertension, dyslipidaemia, CAD, heart failure, and CKD have been associated with an increased risk of CV events. Patients treated with nilotinib and with high- and very high-risk CV (SCORE chart) were noted to have more frequent arterial events [ 43 ].…”

Section: Discussionmentioning

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 Risk and Cardiovascular Events in Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors

Cited by 16 publications

References 29 publications

Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

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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