Hypertension and incident cardiovascular events after next-generation BTKi therapy initiation.

Abstract

BACKGROUND:

Post-market analyses revealed unanticipated links between first-generation Bruton's tyrosine kinase inhibitor (BTKi) therapy, ibrutinib, and profound early hypertension. Yet, whether this is seen with novel selective second (next)-generation BTKi therapy, acalabrutinib, is unknown.

METHODS:

Leveraging a large cohort of consecutive B cell cancer patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence and ramifications of new or worsened hypertension [systolic blood pressure (SBP) ≥ 130 mmHg] after acalabrutinib initiation. Secondary endpoints were major cardiovascular events (MACE: arrhythmias, myocardial infarction, stroke, heart failure, cardiac death) and disease progression. Observed incident hypertension rates were compared to Framingham heart-predicted and ibrutinib-related rates. Multivariable regression and survival analysis were used to define factors associated with new/worsened hypertension and MACE, and the relationship between early SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of acalabrutinib-related hypertension was assessed.

RESULTS:

Overall, from 280 acalabrutinib-treated patients, 48.9% developed new/worsened hypertension over a median of 41 months. The cumulative incidence of new hypertension by 1 year was 53.9%, including 1.7% with high-grade (≥ 3) hypertension. Applying the JNC 8 cutoff BP of ≥ 140/90 mmHg, the observed new hypertension rate was 20.5% at 1 year, > eightfold higher than the Framingham-predicted rate of 2.4% (RR 8.5, P < 0.001), yet 34.1% lower than ibrutinib (12.9 observed-to-expected ratio, P < 0.001). In multivariable regression, prior arrhythmias and Black ancestry were associated with new hypertension (HR 1.63, HR 4.35, P < 0.05). The degree of SBP rise within 1 year of treatment initiation predicted MACE risk (42% HR increase for each + 5 mmHg SBP rise, P < 0.001). No single antihypertensive class prevented worsened acalabrutinib-related hypertension.

CONCLUSIONS:

Collectively, these data suggest that hypertension may be a class effect of BTKi therapies and precedes major cardiotoxic events.

• Authors: Sunnia T Chen, Leylah Azali, Lindsay Rosen, Qiuhong Zhao, Tracy Wiczer, Marilly Palettas, John Gambril, Onaopepo Kola-Kehinde, Patrick Ruz, Sujay Kalathoor, Kerry Rogers, Adam Kittai, Michael Grever, Farrukh Awan, John C Byrd, Jennifer Woyach, Seema A Bhat, Daniel Addison
• Journal: Journal of hematology & oncology (J Hematol Oncol) Vol. 15 Issue 1 Pg. 92 (07 14 2022) ISSN: 1756-8722 [Electronic] England
• PMID: 35836241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2022. The Author(s).

Chemical References

• Antihypertensive Agents

Topics

• Antihypertensive Agents (therapeutic use)
• Blood Pressure
• Humans
• Hypertension (chemically induced, epidemiology)
• Myocardial Infarction
• Stroke (epidemiology, etiology, prevention & control)