Hypertension Treatment in Patients Receiving Ibrutinib: A Multicenter Retrospective Study

• Patients treated for hypertension while taking ibrutinib benefit from combination therapy.

• Regimens that combine HCTZ and beta blockers benefit patients with prior-HTN, while HCTZ and ACEi/ARBs benefit patients with de novo HTN.

Although Bruton's 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 anti-hypertensive drug(s) and with at least 3 months of follow up data were sorted into two groups: those diagnosed with HTN prior to 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 the 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 beta blockers (BBs) with hydrochlorothiazide (HCTZ), (-5.05 mmHg; 95% CI -10.0 to -0.0596; p = 0.047), 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 = 0.05). 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 anti-hypertensives. 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.