International consensus statement on the management of cardiovascular risk of Bruton’s tyrosine kinase inhibitors in CLL

Awan, Farrukh T.; Alfraih, Feras; Baratta, Sergio; Campos, Rodrigo Noronha; Cugliari, María Silvana; Goh, Yeow Tee; Ионин, В. А.; Mundnich, Stefanie; Sverdlov, Aaron L.; Tam, Constantine S.; Ysebaert, Loïc

doi:10.1182/bloodadvances.2022007938

Cited by 26 publications

(35 citation statements)

References 59 publications

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“…Our findings are in line with consensus guidelines, which suggest that ibrutinib can be safely used in many patients with cardiovascular comorbidities provided these conditions are well controlled and appropriately managed. 18 We further evaluated the relation between baseline covariates known to be associated with cardiovascular disease 29 and the risk for hypertensive outcomes in ibrutinib-treated patients. We observed that both older age and male sex were associated with hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…A recently published international consensus statement provides guidelines for the monitoring and management of cardiovascular toxicity in patients with CLL who receive treatment with ibrutinib and other BTK inhibitors. 18 We conducted a retrospective analysis of the cardiovascular effects of ibrutinib treatment after 5 years of follow-up on patients with CLL who were included in clinical trials at The University of Texas MD Anderson Cancer Center. The goal of our study was to assess the long-term effects of chronic ibrutinib exposure on blood pressure (BP), the reversibility of this effect upon discontinuation, and the risk of cardiovascular disease and renal complications.…”

Section: Introductionmentioning

confidence: 99%

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Long‐term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity

Gordon

Jones

George

et al. 2023

Cancer

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Background: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities.Methods: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan-Meier method.Results: Three hundred patients with CLL who were treated with ibrutinib on clinical trials were included. The median patient age at study enrollment was 65 years (range, 29-83 years). Seventy percent of patients were men, and 88% were Caucasian. Sixty-nine percent of patients had hypertension at baseline, and 47% were on antihypertensive medication. Eighty-eight percent had relapsed or refractory CLL. New-onset and worsening hypertension were common, occurring in 68.5% and 38% of patients, respectively. Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg was observed in 16.9% of patients. Hypertension was reversible after ibrutinib discontinuation. Older age, male sex, tobacco use, and chronic kidney disease were associated with ibrutinib-related hypertension. Baseline hypertension was not associated with major adverse cardiovascular events in ibrutinib-treated patients nor with event-free or overall survival. Conclusions:Hypertension is a common toxicity in patients with CLL who receive ibrutinib but is manageable in most patients. Other than chronic kidney disease, baseline cardiovascular disease did not affect ibrutinib-related hypertension nor was hypertension associated with major adverse cardiovascular events or survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long‐term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity

Gordon

Jones

George

et al. 2023

Cancer

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“…84,116 Overall BTKi have shown dramatically better efficacy across a range of hematological malignancies than traditional chemoimmunotherapies and are well tolerated, however, accumulating data have revealed multiple adverse events, including CVAE. 117…”

Section: Bruton Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

“…121 In addition, ibrutinib has been associated with other cardiovascular toxicities including atrial fibrillation and bleeding; however, next-generation, more selective BTKi (acalabrutinib and zanubrutinib) seem to have an overall lower cardiovascular toxicity, including hypertension. 117 Like ibrutinib, acalabrutinib (second-generation BTKi) was also trialed in refractory CLL patients and similarly demonstrated a treatment-related hypertensive incidence of 7%. 123 However, more recent experience with acalabrutinib from the ELEVATE-TN (Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia) trial 124 and also the ASCEND (Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia) trial 125 suggests lower rates of hypertension, with comparable rates of all-grade and severe-grade hypertension as control treatment groups.…”

Section: Clinical and Epidemiological Evidence For Btki-induced Hyper...mentioning

confidence: 99%

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

et al. 2023

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Cardiovascular disease and cancer are 2 of the leading causes of death worldwide. Although improvements in outcomes have been noted for both disease entities, the success of cancer therapies has come at the cost of at times very impactful adverse events such as cardiovascular events. Hypertension has been noted as both, a side effect as well as a risk factor for the cardiotoxicity of cancer therapies. Some of these dynamics are in keeping with the role of hypertension as a cardiovascular risk factor not only for heart failure, but also for the development of coronary and cerebrovascular disease, and kidney disease and its association with a higher morbidity and mortality overall. Other aspects such as the molecular mechanisms underlying the amplification of acute and long-term cardiotoxicity risk of anthracyclines and increase in blood pressure with various cancer therapeutics remain to be elucidated. In this review, we cover the latest clinical data regarding the risk of hypertension across a spectrum of novel anticancer therapies as well as the underlying known or postulated pathophysiological mechanisms. Furthermore, we review the acute and long-term implications for the amplification of the development of cardiotoxicity with drugs not commonly associated with hypertension such as anthracyclines. An outline of management strategies, including pharmacological and lifestyle interventions as well as models of care aimed to facilitate early detection and more timely management of hypertension in patients with cancer and survivors concludes this review, which overall aims to improve both cardiovascular and cancer-specific outcomes.

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“…Because the FDA label for ibrutinib recently was amended to include a warning regarding fatal and serious cardiac arrhythmias that can occur with ibrutinib therapy, particular attention should be paid to any differences in cardiovascular events that may emerge across combination studies with different generation BTKi partners. Expert recommendations currently counsel physicians to avoid BTKis (particularly ibrutinib) in patients with a history of ventricular arrythmias, 66 thus doublet or triplet therapy with BTKis may not be appropriate for all patients. Further long‐term follow‐up data are required to elucidate the risk of these events with frontline therapy using second‐generation agents, and forthcoming data from larger combination studies (e.g., ACE‐CL‐311) will be of particular interest.…”

Section: Safety Profilementioning

confidence: 99%

Novel combination approaches with targeted agents in frontline chronic lymphocytic leukemia

Lipsky

Lamanna

2022

Cancer

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Targeted therapies have revolutionized the frontline treatment landscape for patients with chronic lymphocytic leukemia (CLL) and have largely displaced a reliance on chemoimmunotherapy when treating this disease. Multiple randomized trials have documented the efficacy of oral therapy with the Bruton tyrosine kinase inhibitors ibrutinib and acalabrutinib (and zanubrutinib, pending a supplemental new drug application in CLL), as well as BCL2 inhibition using venetoclax. In this review, the authors highlight novel therapeutic strategies for using these agents in combination, either as doublet therapy or as triplet therapy, with anti-CD20 antibodies.First, the current treatment landscape is outlined, and the data are reviewed for continuous and time-limited therapeutic approaches, which constitute the current standard of care. Then, more recent reports are described from phase 2 and 3 studies exploring different combination strategies of Bruton tyrosine kinase and BCL2 inhibition for treatment-naive patients. In addition, relevant differences are emphasized between patient characteristics (e.g., patient fitness and the presence of high-risk disease features) and study methodology (e.g., dosing schedule, randomization, and assessment of measurable residual disease) across trials. Finally, the authors revisit the currently available data for these approaches in the context of ongoing studies and future planned trials, evaluating their potential impact on the frontline treatment landscape for CLL in the years to come.

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International consensus statement on the management of cardiovascular risk of Bruton’s tyrosine kinase inhibitors in CLL

Cited by 26 publications

References 59 publications

Long‐term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity

Long‐term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

Novel combination approaches with targeted agents in frontline chronic lymphocytic leukemia

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