Hypertension and incident cardiovascular events following ibrutinib initiation

Dickerson, Tyler; Wiczer, Tracy; Waller, Allyson; Philippon, J; Porter, Kyle; Haddad, Devin; Guha, Avirup; Rogers, Kerry A.; Bhat, Seema A.; Byrd, John C.; Woyach, Jennifer A.; Awan, Farrukh T.; Addison, Daniel

doi:10.1182/blood.2019000840

Cited by 190 publications

(188 citation statements)

References 44 publications

(66 reference statements)

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“…Nevertheless, this would only be true for milder AEs, as the more severe AEs were always reported. We identified 6.8% patients with any grade hypertension, which is remarkably lower than previously reported; a recent study reported 71.6% patients developing de novo hypertension during ibrutinib treatment, 20 whereas in the RESONATE and RESONATE‐2 studies 21%‐26% reported hypertension 15,21 . The difference probably reflects the retrospective nature of this study and that hypertension primarily is managed in general practice, thus not fully documented in hospital records.…”

Section: Discussioncontrasting

confidence: 65%

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

Aarup

Rotbain

Enggaard

et al. 2020

European J of Haematology

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Ibrutinib has now been approved for treatment of chronic lymphocytic leukemia (CLL) in both front-line setting and as later-line treatment. However, knowledge about the outcomes and adverse events (AE) among patients at a population-based level is still limited. Objectives: To report outcomes and AEs in a population-based cohort treated with ibrutinib outside clinical trials. Methods: We conducted a multicenter, retrospective cohort study including all patients with CLL treated with ibrutinib. Results: In total, 205 patients were included of whom 39 (19%) were treatment-naïve. The median follow-up was 21.4 months (interquartile range (IQR), 11.9, 32.8), the estimated overall survival at 12 months was 88.8% (95% confidence interval (CI); 84.3%, 93.3%), and the estimated progression-free survival at 12 months was 86.3% (95% CI; 81.3%, 91.2%). During follow-up, 200 (97.6%) patients had at least one AE and 100 (48.8%) patients had at least one grade ≥3 AE. Eighty-six patients (42.0%) discontinued ibrutinib, hereof 47 (54.7%) due to AEs and 19 (22.1%) had progression of CLL or Richter transformation. Conclusions: In our study, we find comparable, though slightly inferior, overall, and progression-free survival, and discontinuation due to toxicity was higher compared with clinical trials. Patient training and information may improve treatment adherence outside clinical trials.

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Section: Discussioncontrasting

confidence: 65%

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

Aarup

Rotbain

Enggaard

et al. 2020

European J of Haematology

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“…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

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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%.

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“…1,2 A recent retrospective analysis of 562 patients receiving ibrutinib at the Ohio State University also noted a marked incidence of new hypertension of 72%. 7 Major cardiac events were noted in 17% of patients and occurred more frequently in those with new or worsening hypertension (19%). In a separate aggregated data set of over 1000 patients receiving ibrutinib, 10 events of sudden death or cardiac arrest were identified.…”

Section: Resultsmentioning

confidence: 99%

<p>The Impact of Age on Survival in CLL Patients Receiving Ibrutinib as Initial Therapy</p>

Ujjani

Mato

Hill

et al. 2020

BLCTT

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Introduction: Recent randomized trials have demonstrated the efficacy of ibrutinib-based therapy in the treatment of patients with CLL. In Alliance A041202, a higher than expected number of unexplained deaths were reported with front-line ibrutinib in a patient population aged at least 65 years compared to ECOG 1912, which included patients up to 70 years of age. Methods: Therefore, we conducted a retrospective analysis to investigate whether ibrutinib was associated with a greater mortality in older patients outside of a clinical trial setting. This multicenter analysis was performed by investigators at 20 academic and community practices. Results: Amongst the 391 patients included, there was no correlation between age and response rate, PFS, or OS. However, there was a trend to higher rate of deaths in patients >65years-old (8.7% vs 3.8%, p=0.097), with an increased number of early deaths (13 vs 4, p=0.3). Conclusion: These data suggest greater intolerance, and possibly mortality, with ibrutinib in an older population. Patients should be educated regarding the potential complications related to ibrutinib and symptoms of concern to report.

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Hypertension and incident cardiovascular events following ibrutinib initiation

Cited by 190 publications

References 44 publications

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

Real‐world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib

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

<p>The Impact of Age on Survival in CLL Patients Receiving Ibrutinib as Initial Therapy</p>

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