TY - JOUR
T1 - Hypertension and incident cardiovascular events following ibrutinib initiation
AU - Dickerson, Tyler
AU - Wiczer, Tracy
AU - Waller, Allyson
AU - Philippon, Jennifer
AU - Porter, Kyle
AU - Haddad, Devin
AU - Guha, Avirup
AU - Rogers, Kerry A.
AU - Bhat, Seema
AU - Byrd, John C.
AU - Woyach, Jennifer A.
AU - Awan, Farrukh
AU - Addison, Daniel
N1 - Funding Information:
The authors thank the patients and their families treated at The Ohio State University Comprehensive Cancer Center. This work was supported, in part, by National Institutes of Health (NIH), National Cancer Institute grants K23-CA178183 (J.A.W.), R01-CA197870 (J.C.B. and J.A.W.), R35-CA197734 (J.C.B.), and K12-CA133250 (D.A. and J.C.B.). Support was also received from the D. Warren Brown Foundation, the Four Winds Foundations, and the Connie Brown CLL Foundation. The article’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. J.C.B. received research funding and consulted for Acerta Pharma and Pharmacyclics. F.A. received research funding from Innate Pharma and Pharmacyclics; has provided consulting services to Gilead Sciences, Pharmacyclics, Janssen, Abbvie, Sunesis, AstraZeneca, Genentech, and Novartis Oncology; and has served on the speakers’ bureau of Abbvie and AstraZeneca. K.A.R. received research funding from Genentech and served on an advisory board for Acerta Pharma. J.A.W. received research funding from Abbvie, Pharmacyclics, Janssen, Acerta, Loxo, Karyopharm, and Morphosys and has consulted for Janssen and Pharmacyclics. The remaining authors declare no competing financial interests.
Funding Information:
This work was supported, in part, by National Institutes of Health (NIH), National Cancer Institute grants K23-CA178183 (J.A.W.), R01-CA197870 (J.C.B. and J.A.W.), R35-CA197734 (J.C.B.), and K12-CA133250 (D.A. and J.C.B.). Support was also received from the D. Warren Brown Foundation, the Four Winds Foundations, and the Connie Brown CLL Foundation.
Funding Information:
Conflict-of-interest disclosure: J.C.B. received research funding and consulted for Acerta Pharma and Pharmacyclics. F.A. received research funding from Innate Pharma and Pharmacyclics; has provided consulting services to Gilead Sciences, Pharmacyclics, Janssen, Abbvie, Sunesis, AstraZeneca, Genentech, and Novartis Oncology; and has served on the speakers’ bureau of Abbvie and AstraZeneca. K.A.R. received research funding from Genentech and served on an advisory board for Acerta Pharma. J.A.W. received research funding from Abbvie, Pharmacyclics, Janssen, Acerta, Loxo, Karyopharm, and Morphosys and has consulted for Janssen and Pharmacyclics. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019
Y1 - 2019
N2 - Ibrutinib is associated with dramatic efficacy against B-cell malignancies. Yet, it has been linked with potentially limiting cardiotoxicity, including emerging reports of profound hypertension (HTN). The long-term incidence, severity, and impact of HTN development with ibrutinib are unknown. Therefore, in 562 consecutive patients treated with ibrutinib for B-cell malignancies from 2009 through 2016, we assessed the new/incident or worsened HTN (systolic blood pressure [BP] cutoff, 130 mm Hg). Observed incident HTN rates were compared with Framingham-heart–predicted incident HTN rates. We also evaluated the relationship of HTN to the development of other major adverse cardiovascular events (MACEs), including arrhythmia, myocardial infarction, stroke, heart failure, and cardiovascular death. Further, we assessed the effects of different antihypertensive classes on ibrutinib-related HTN. Overall, 78.3% of ibrutinib users developed new or worsened HTN over a median of 30 months. New HTN developed in 71.6% of ibrutinib users, with a time to 50% cumulative incidence of 4.2 months. Among those without preceding HTN, 17.7% developed high-grade HTN (BP >160/100 mm Hg). In multivariate regression, new or worsened HTN was associated with increased MACEs (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.08-4.38). No single antihypertensive class was associated with prevention or control of ibrutinib-related HTN. However, antihypertensive initiation was associated with a lower risk of a MACE (HR, 0.40; 95% CI, 0.24-0.66). Collectively, these data suggest that ibrutinib is associated with a substantial increase in the incidence and severity of HTN, and that HTN development carries a higher risk of subsequent cardiotoxic events.
AB - Ibrutinib is associated with dramatic efficacy against B-cell malignancies. Yet, it has been linked with potentially limiting cardiotoxicity, including emerging reports of profound hypertension (HTN). The long-term incidence, severity, and impact of HTN development with ibrutinib are unknown. Therefore, in 562 consecutive patients treated with ibrutinib for B-cell malignancies from 2009 through 2016, we assessed the new/incident or worsened HTN (systolic blood pressure [BP] cutoff, 130 mm Hg). Observed incident HTN rates were compared with Framingham-heart–predicted incident HTN rates. We also evaluated the relationship of HTN to the development of other major adverse cardiovascular events (MACEs), including arrhythmia, myocardial infarction, stroke, heart failure, and cardiovascular death. Further, we assessed the effects of different antihypertensive classes on ibrutinib-related HTN. Overall, 78.3% of ibrutinib users developed new or worsened HTN over a median of 30 months. New HTN developed in 71.6% of ibrutinib users, with a time to 50% cumulative incidence of 4.2 months. Among those without preceding HTN, 17.7% developed high-grade HTN (BP >160/100 mm Hg). In multivariate regression, new or worsened HTN was associated with increased MACEs (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.08-4.38). No single antihypertensive class was associated with prevention or control of ibrutinib-related HTN. However, antihypertensive initiation was associated with a lower risk of a MACE (HR, 0.40; 95% CI, 0.24-0.66). Collectively, these data suggest that ibrutinib is associated with a substantial increase in the incidence and severity of HTN, and that HTN development carries a higher risk of subsequent cardiotoxic events.
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U2 - 10.1182/blood.2019000840
DO - 10.1182/blood.2019000840
M3 - Article
C2 - 31582362
AN - SCOPUS:85075812906
SN - 0006-4971
VL - 134
SP - 1919
EP - 1928
JO - Blood
JF - Blood
IS - 22
ER -