Once weekly selinexor,carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients

Background Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).Methods The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m²) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib.Results Thirty-two patients, median prior therapies 4 (range, 1–8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m², and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months.Conclusions Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.Subject terms: Myeloma, Drug development     

Right ventricular failure in patients with preserved ejection fraction and diastolic dysfunction: an underrecognized clinical entity

It is well recognized that patients with severe left ventricular (LV) systolic dysfunction develop pulmonary venous hypertension or postcapillary pulmonary hypertension, which leads to an increase in pulmonary vascular resistance (PVR) and right ventricular (RV) systolic failure. It is often underrecognized, however, that patients with heart failure with preserved LV ejection fraction and diastolic dysfunction may also develop postcapillary pulmonary hypertension with elevated PVR leading to RV systolic failure. This form of biventricular failure is a result of diastolic failure on the left in patients with preserved LV ejection fraction and systolic failure on the right. At this time, there are no randomized trials or guidelines addressing the management of patients with diastolic heart failure with and without resultant RV failure. The authors review the pathophysiology, clinical presentation, and suggested treatment of this underrecognized clinical entity.     

Congenital Absence of the Left Atrial Appendage Visualized by 3D Echocardiography in Two Adult Patients

Congenital absence of left atrial appendage (LAA) is an extremely rare condition and its physiological consequences are unknown. We present two cases of incidental finding of a congenitally absent LAA in a 79‐year‐old male who presented for routine transesophageal echocardiogram (TEE) to rule out intracardiac thrombus prior to placement of biventricular implantable cardioverter‐defibrillator and a 54‐year old female who presented for TEE prior to radiofrequency ablation of atrial fibrillation. Characterization of patients with such an absence is important because congenitally absent LAA may be confused with flush thrombotic occlusion of the appendage. There are very few published reports of congenital absence of LAA. To our knowledge, our report is the first to demonstrate the congenital absence of LAA by 3D transesophageal echocardiography.     

Subacute left ventricular outflow tract obstruction after transapical closure of a mitral paravalvular leak in the region of the aortomitral curtain

We report a rare case of progressive left ventricular outflow tract (LVOT) obstruction after percutaneous device closure of a mechanical prosthetic mitral valve (MV) paravalvular leak (PVL) in the region of aortomitral curtain in a patient who also had small mechanical aortic valve prosthesis with patient–prosthesis mismatch.     

Optical coherence tomography reflects clinically relevant gray matter damage in patients with multiple sclerosis

Journal of Neurology - Retinal degeneration leading to optical coherence tomography (OCT) changes is frequent in patients with multiple sclerosis (PwMS). To investigate associations among OCT...