Hypertension treatment for patients receiving ibrutinib: a multicenter retrospective study.

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 ß 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.

Dabrafenib and Trametinib Treatment for Erdheim-Chester Disease With Brain Stem Involvement.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by infiltration of organs by CD68+ and CD1a- lipid-laden histiocytes, including the central nervous system in more than a third of patients. Molecular analysis of ECD samples has demonstrated the prevalence of BRAF V600E mutations as high as 54%. Recently, vemurafenib became the only Food and Drug Administration-approved treatment for patients with ECD who carry the BRAF V600E mutation. However, dabrafenib has been suggested to have greater brain distribution. We describe a 44-year-old female patient treated from August of 2015 through November 2017. She presented with a 2-year history of light-headedness, fatigue, and vertigo. She was moderately dysmetric, diffusely hyperreflexic, and dysarthric in the bilateral upper and lower extremities. Her gait was wide-based. She had dysarthria and nystagmus on horizontal gaze bilaterally. Magnetic resonance imaging showed an extensive area of increased T2/fluid-attenuated inversion recovery signal in the brain stem, enhancement in the pons and midbrain, and thickening of the pituitary stalk. Positron emission tomography/computed tomography (PET/CT) and whole-body technetium Tc99m bone scintigraphy showed intense symmetrical radiotracer uptake in the distal femur and tibia bilaterally, which was biopsied. Immunohistochemistry was negative for BRAF V600E, but genomic sequencing revealed the mutation. The patient received combination therapy with dabrafenib and trametinib. Her nystagmus, dysarthria, dysmetria, and gait improved remarkably. Subsequent PET/CT and magnetic resonance imaging showed complete resolution of all radiographic evidence of disease. In this case report, we demonstrate the success of a combination therapy with dabrafenib and trametinib.

Magnetic Resonance-Guided Laser Ablation for the Treatment of Recurrent Dural-Based Lesions: A Series of Five Cases.

BACKGROUND AND OBJECTIVE: Magnetic resonance-guided laser-induced thermotherapy (MR-LITT) is a minimally invasive technique that shows promise in neuro-oncology because of its superiority in delivering precise minimally invasive thermal energy with minimal collateral damage. In this analysis, we investigate initial data on the effect of MR-LITT on dural-based lesions. METHODS: Five patients were identified with dural-based lesions (4 meningiomas, 1 solitary fibrous tumor) with clear evidence of radiologic progression. In all 5 cases, the tumors were localized to the lateral convexity or paramedian locations in the supratentorial space. All patients received MR-LITT and then a follow-up magnetic resonance imaging scan at 24 hours after treatment, at 1 month, and at each subsequent follow-up visit. Local control of the ablated tumor was evaluated with radiographic follow-up and symptomatic progression-free survival was recorded. RESULTS: Five LITT treatments were performed on 5 patients with an average age of 65.2 years. The average tumor volume was 29.7 cm3 and ablation dosage was 12.4 W. On average, 80% of the pretreatment lesion volume was ablated. The mean follow-up time was 59.3 weeks. In total, 2 patients (1 with an anaplastic meningioma and 1 with a solitary fibrous tumor) had radiographic evidence of disease progression. In the observed time of the 3 patients with no progression, there was a 52% reduction in tumor volume. There were no major perioperative complications. CONCLUSIONS: MR-LITT is a promising technology for dural-based lesion treatment. This initial study demonstrates that MR-LITT is safe and offers several advantages over open surgical treatment. Randomized studies are needed to evaluate its role as a treatment adjunct.