Hypertension treatment for patients receiving ibrutinib: a multicenter retrospective study
Laura Samples, Jenna Voutsinas, Bita Fakhri, Sirin Khajavian, Stephen E. Spurgeon, Deborah M. Stephens, Alan P Skarbnik, Anthony R. Mato, Catherine M. Broome, Ajay K. Gopal, Stephen D. Smith, Ryan C. Lynch, Magdalena A. Rainey, Myung Sun Kim, Odeth Barrett-Campbell, Emily Hemond, Mazie Tsang, Daniel A. Ermann, Nikita Malakhov, Danielle Rao, Mehrdad Shakib-Azar, Beth Morrigan, Ayushi Chauhan, Thomas Plate, Ted Gooley, Kellie Ryan, Frederick Lansigan, Brian T. Hill, Georgios Pongas, Sameer A. Parikh, Lindsey E. Roeker, John N. Allan, Richard K. Cheng, Chaitra S. Ujjani, Mazyar Shadman
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.