A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Objective: We evaluated ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who had received 1-3 prior therapies. Methods: This was a phase 2, single-arm, open-label, multicentre study (NCT02902965). The primary endpoint was progression-free survival (PFS). Results: Seventy-six patients were enrolled; 74 received ≥1 dose of study treatment. After median follow-up of 19.6 months, median PFS was 8.5 months (95% CI: 6.2-10.8); median overall survival was not reached. Overall response rate was 57% (95% CI: 45-68), and median duration of response was 9.5 months (95% CI: 6.9-10.6). Grade 3/4 AEs occurred in 73% of patients and fatal AEs occurred in 15% of patients. Incidence of major haemorrhage was 5%; one patient died from cerebral haemorrhage. After an observed increased incidence of serious (42%) and fatal (11%) infections, enrolment was suspended to implement risk-minimisation measures. The safety profile was otherwise consistent with known safety profiles of the individual drugs. Conclusion: Ibrutinib combined with bortezomib and dexamethasone elicited clinical responses. However, efficacy assessments conducted at potential restart of enrolment indicated that the targeted PFS could not be reached with additional patient enrolment, and the study was terminated

Comparison of the magnetic resonance imaging and acoustocerebrography signals in the assessment of focal cerebral microangiopathic lesions in patients with asymptomatic atrial fibrillation. (Preliminary clinical study results)

Acoustocerebrography (ACG) is a set of techniques designed to capture states of human brain tissue, and its changes. It is based on noninvasive measurements of various parameters obtained by analyzing an ultrasound pulse emitted through the human’s skull. ACG and Magnetic Resonance Imaging (MRI) results were compared in a clinical study assessment of focal white-matter-lesions (WML) in the brains of patients with asymptomatic atrial fibrillation (AAF). The clinical study included 55 patients (age 66.1 ± 6.7 years). According to MRI data, the patients were assigned into four groups depending on the number of lesions: L0 - 0 to 4 lesions, L5 - 5 to 9 lesions, L10 - 10 to 29 lesions, and L30 - 30 or more lesions. As a result, it has been concluded that the ACG method could clearly differentiate the groups L0 (with 0 ÷ 4 lesions) and L30 (with more than 30 lesions) of WML patients. Fisher’s Exact Test shows that this correlation is highly significant (p < 0.001). ACG seems to be a new, effective, method for detecting WML for patients with AAF and can become increasingly useful in both diagnosing, and in stratifying, them. This, in turn, can be helpful in individualizing their treatment, so that the risk of strokes may become essentially reduced