Hypertension treatment for patients receiving ibrutinib: a multicenter retrospective study

Author:

Samples Laura12ORCID,Voutsinas Jenna1,Fakhri Bita3ORCID,Khajavian Sirin1,Spurgeon Stephen4,Stephens Deborah5ORCID,Skarbnik Alan6,Mato Anthony7,Broome Catherine8,Gopal Ajay12ORCID,Smith Stephen12ORCID,Lynch Ryan12,Rainey Magdalena9ORCID,Kim Myung Sun4,Barrett-Campbell Odeth10,Hemond Emily10,Tsang Mazie3ORCID,Ermann Daniel5,Malakhov Nikita11,Rao Danielle7,Shakib-Azar Mehrdad1,Morrigan Beth1,Chauhan Ayushi12ORCID,Plate Thomas13,Gooley Ted1,Ryan Kellie14,Lansigan Frederick10ORCID,Hill Brian9,Pongas Georgios13,Parikh Sameer A.15ORCID,Roeker Lindsey7ORCID,Allan John N.11ORCID,Cheng Richard16ORCID,Ujjani Chaitra12ORCID,Shadman Mazyar12

Affiliation:

1. 1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA

2. 2Division of Hematology and Oncology, University of Washington, Seattle, WA

3. 3Division of Hematology and Oncology, University of California, San Francisco, CA

4. 4Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR

5. 5Division of Hematology and Hematologic Malignancies, The University of Utah, Salt Lake City, UT

6. 6Novant Health, Charlotte, NC

7. 7Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY

8. 8Division of Hematology and Oncology, Georgetown University, Washington, DC

9. 9Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH

10. 10Hematology/Oncology Section, Dartmouth-Hitchcock Medical Center, Lebanon, NH

11. 11Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY

12. 12Division of Hematology and Oncology, Georgia Cancer Center, Augusta University, Augusta, GA

13. 13Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL

14. 14AstraZeneca, Gaithersburg, MD

15. 15Department of Hematology, Mayo Clinic, Rochester, MN

16. 16Division of Cardiology, University of Washington, Seattle, WA

Abstract

Abstract Although Bruton tyrosine kinase inhibitors (BTKis) are generally well tolerated and less toxic than chemotherapy alternatives used to treat lymphoid malignancies, BTKis like ibrutinib have the potential to cause new or worsening hypertension (HTN). Little is known about the optimal treatment of BTKi-associated HTN. Randomly selected patients with lymphoid malignancies on a BTKi and antihypertensive drug(s) and with at least 3 months of follow-up data were sorted into 2 groups: those diagnosed with HTN before BTKi initiation (prior-HTN), and those diagnosed with HTN after BTKi initiation (de novo HTN). Generalized estimating equations assessed associations between time varying mean arterial pressures (MAPs) and individual anti-HTN drug categories. Of 196 patients included in the study, 118 had prior-HTN, and 78 developed de novo HTN. Statistically significant mean MAP reductions were observed in patients with prior-HTN who took β blockers (BBs) with hydrochlorothiazide (HCTZ), (−5.05 mmHg; 95% confidence interval [CI], 10.0 to −0.0596; P = .047), and patients diagnosed with de novo HTN who took either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) with HCTZ (−5.47 mmHg; 95% CI, 10.9 to −0.001; P = .05). These regimens also correlated with the greatest percentages of normotensive MAPs. Treatment of HTN in patients taking a BTKi is challenging and may require multiple antihypertensives. Patients with prior-HTN appear to benefit from combination regimens with BBs and HCTZ, whereas patients with de novo HTN appear to benefit from ACEi/ARBs with HCTZ. These results should be confirmed in prospective studies.

Publisher

American Society of Hematology

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