Impact of venetoclax monotherapy on the quality of life of patients with relapsed or refractory chronic lymphocytic leukemia: results from the phase 3b VENICE II trial.

Venetoclax, a potent B-cell lymphoma-2 (BCL-2) inhibitor, has demonstrated clinical efficacy in chronic lymphocytic leukemia (CLL). VENICE II is an open-label, single-arm, phase 3b study (NCT02980731) evaluating the impact of venetoclax monotherapy (400 mg once daily) for ≤2 years on health-related quality of life (HRQoL) of patients with relapsed/refractory CLL. The primary endpoint was mean change in the global health status (GHS)/quality of life (QoL) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) from baseline to Week 48.

Posterior brain sensorimotor recruitment for inhibition of delayed responses in children.

Inhibitory control, the ability to suppress irrelevant thoughts or actions, is central to cognitive and social development. Protracted maturation of frontal brain networks has been reported as a major restraint for this ability, yet, young children, when motivated, successfully inhibit delayed responses. A better understanding of the age-dependent neural inhibitory mechanism operating during the awaiting-to-respond window in children may elucidate this conundrum.

Efficacy of venetoclax plus rituximab for relapsed CLL: 5-year follow-up of continuous or limited- duration therapy.

We report long-term follow-up of the phase 1b study of venetoclax and rituximab (VenR) in patients with relapsed chronic lymphocytic leukemia (CLL), including outcomes with continuous or limited-duration therapy. Patients received venetoclax daily (200-600 mg) and rituximab over 6 months and then received venetoclax monotherapy. Patients achieving complete response (CR), CR with incomplete marrow recovery (CRi), or undetectable minimal residual disease (uMRD) assessed by flow cytometry (<10-4 cutoff) were allowed, but not required, to discontinue therapy, while remaining in the study and could be retreated with VenR upon progression.

Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study.

Purpose: We previously reported a 44% overall response rate (ORR) with the oral BCL-2 inhibitor venetoclax in a phase I study of relapsed/refractory non-Hodgkin lymphoma (NHL). Complete response (CR) was observed in patients with mantle cell lymphoma [(MCL), 21%, = 6/28] and follicular lymphoma [(FL), 17%, = 5/29], and partial response (PR) noted in several patients with Waldenström macroglobulinemia (WM), and marginal zone lymphoma (MZL). Here, we report the long-term outcomes of these four cohorts.

Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma.

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-X/BCL2 inhibitor, may allow targeting of both BCL2 and BCL-X without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment.

Targeting BCL-2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma.

Venetoclax (Ven) is a selective small-molecule inhibitor of BCL-2 that exhibits antitumoral activity against MM cells with t(11;14) translocation. We evaluated the safety and efficacy of Ven and dexamethasone (VenDex) combination in patients with t(11;14) positive relapsed/refractory (R/R) multiple myeloma (MM). This open-label, multicenter study had two distinct phases (phase one [P1], phase two [P2]).

Safety and efficacy of navitoclax, a BCL-2 and BCL-X inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study.

Navitoclax, a novel BCL-2 and BCL-X inhibitor, demonstrated promising antitumor activity in the dose-escalation part of a phase 1/2a study (NCT00406809) in lymphoid tumors. Herein, we report the continued safety and efficacy results of the phase 2a portion. Twenty-six adult patients with relapsed/refractory follicular lymphoma ( = 11, Arm A) and other relapsed/refractory lymphoid malignancies ( = 15, Arm B) were enrolled.

MMP-9 inhibitors impair learning in spontaneously hypertensive rats.

Vascular cognitive impairment dementia (VCID) is a major cause of cognitive loss in the elderly. Matrix metalloproteinases (MMPs) are a family of proteases involved in remodeling the extracellular matrix in development, injury and repair. Blood-brain barrier (BBB) disruption due to inflammation mediated by MMPs is a mechanism of white matter injury.

Hypoxia promotes tau hyperphosphorylation with associated neuropathology in vascular dysfunction.

Background: Hypertension-induced microvascular brain injury is a major vascular contributor to cognitive impairment and dementia. We hypothesized that chronic hypoxia promotes the hyperphosphorylation of tau and cell death in an accelerated spontaneously hypertensive stroke prone rat model of vascular cognitive impairment.

Methods: Hypertensive male rats (n = 13) were fed a high salt, low protein Japanese permissive diet and were compared to Wistar Kyoto control rats (n = 5).

Biomarkers identify the Binswanger type of vascular cognitive impairment.

Binswanger's disease is a form of subcortical ischemic vascular disease (SIVD-BD) with extensive white matter changes. To test the hypothesis that biomarkers could improve classification of SIVD-BD, we recruited 62 vascular cognitive impairment and dementia (VCID) patients. Multimodal biomarkers were collected at entry into the study based on clinical and neuropsychological testing, multimodal magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis.