Hypertension in Patients Treated With Ibrutinib for Chronic Lymphocytic Leukemia

Roeker, Lindsey E.; Yazdy, Maryam Sarraf; Rhodes, Joanna; Goodfriend, Julie M.; Narkhede, Mayur; Carver, Joseph R.; Mato, Anthony R.

doi:10.1001/jamanetworkopen.2019.16326

Cited by 23 publications

(21 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, only 4.9% of the patients developed ibrutinib‐associated new‐onset or increased hypertension according to a defined causality assessment, which is lower than previously reported 41,42 . However, due to the non‐uniform recording of blood pressure values in medical files, the incidence of new‐onset or increased hypertension could be under‐estimated.…”

Section: Discussioncontrasting

confidence: 71%

Patterns of use and safety of ibrutinib in real‐life practice

Allouchery

Tomowiak

Guidez

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims To provide real‐life data on patterns of use and safety of ibrutinib. Methods A cohort study including all patients initiating ibrutinib between 21 November 2014 and 21 November 2018, and followed for 1 year was conducted. Patient characteristics, ibrutinib use and adverse drug reactions (ADRs) were collected from medical records. Kaplan–Meier analysis estimated the probability of developing ibrutinib‐associated serious ADRs (SADRs) with a 95% confidence interval (CI). A Cox proportional hazards model was used to investigate factors associated with SADR occurrence. Results In total, 102 patients were included in the study. The median age was 70.3 years (interquartile range 64.7–75.6), the male/female gender ratio was 2.9. Almost half the patients (47.1%) were prescribed ibrutinib for chronic lymphocytic leukaemia (CLL). Forty‐three patients (42.1%) permanently discontinued ibrutinib in the first year, mostly for progression (51.2%) or ADRs (32.6%). Forty‐eight patients (47.1%) experienced at least one ibrutinib‐associated SADR. Haematological, infectious and vascular disorders were the most frequent SADRs. The probability of developing ibrutinib‐associated SADR was 35.1% (95% CI 26.3–45.7%) at 3 months, 44.8% (35.2%; 55.8%) at 6 months and 54.3% (44.0%; 65.2%) at 12 months. Age ≥80 years (hazard ratio [HR] 2.03; 95% CI 1.02–4.05) and CLL (HR 1.81; 95% CI 1.01–3.25) were significantly associated with a higher risk of SADR occurrence. Conclusion This study found a high cumulative incidence of ibrutinib‐associated SADRs within the first year of treatment. In view of the risk of SADR, patients aged ≥80 years or treated for CLL deserve special attention.

show abstract

Section: Discussioncontrasting

confidence: 71%

Patterns of use and safety of ibrutinib in real‐life practice

Allouchery

Tomowiak

Guidez

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Ibrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase, is indicated in advanced B-cell malignancy. It is implicated in new onset hypertension in 49% and CTCAE grade 3 hypertension in 16% [ 45 , 46 , 47 , 48 , 49 ].…”

Section: Hypertensive Cardiotoxicities Of Cancer Therapiesmentioning

confidence: 99%

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Chung

Tyebally

Chen

et al. 2020

JCM

View full text Add to dashboard Cite

Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

show abstract

“…Ibrutinib is a distinct small molecule TKI which acts not via VSP but by selectively and irreversibly inhibiting Bruton tyrosine kinase (BTK) and preventing chemokine-induced adhesion and migration. Ibrutinib has also been observed to cause new-onset or worsening hypertension in 18% of patients and grade 3 or 4 hypertension in 6% of patients with CLL [ 76 ]. The mechanism of hypertension and its management strategies are yet to be clarified.…”

Section: Cancer Therapies With the Potential To Cause Hypertensionmentioning

confidence: 99%

Etiology and management of hypertension in patients with cancer

et al. 2021

View full text Add to dashboard Cite

The pathophysiology of hypertension and cancer are intertwined. Hypertension has been associated with an increased likelihood of developing certain cancers and with higher cancer-related mortality. Moreover, various anticancer therapies have been reported to cause new elevated blood pressure or worsening of previously well-controlled hypertension. Hypertension is a well-established risk factor for the development of cardiovascular disease, which is rapidly emerging as one of the leading causes of death and disability in patients with cancer. In this review, we discuss the relationship between hypertension and cancer and the role that hypertension plays in exacerbating the risk for anthracycline- and trastuzumab-induced cardiomyopathy. We then review the common cancer therapies that have been associated with the development of hypertension, including VEGF inhibitors, small molecule tyrosine kinase inhibitors, proteasome inhibitors, alkylating agents, glucocorticoids, and immunosuppressive agents. When available, we present strategies for blood pressure management for each drug class. Finally, we discuss blood pressure goals for patients with cancer and strategies for assessment and management. It is of utmost importance to maintain optimal blood pressure control in the oncologic patient to reduce the risk of chemotherapy-induced cardiotoxicity and to decrease the risk of long-term cardiovascular disease.

show abstract

Hypertension in Patients Treated With Ibrutinib for Chronic Lymphocytic Leukemia

Abstract: This cohort study describes patterns of development, management strategies, and long-term vascular consequences of hypertension associated with ibrutinib in the non–clinical trial setting.

Cited by 23 publications

References 3 publications

Patterns of use and safety of ibrutinib in real‐life practice

Patterns of use and safety of ibrutinib in real‐life practice

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Etiology and management of hypertension in patients with cancer

Contact Info

Product

Resources

About