Objective Elotuzumab plus lenalidomide and dexamethasone (ELd) was approved in Japan in 2016 for the treatment of relapsed/refractory multiple myeloma (RRMM). This post-marketing surveillance study evaluated the safety and effectiveness of ELd in RRMM patients during routine clinical practice in Japan. Methods Elotuzumab safety was assessed by evaluating adverse drug reactions (ADRs), and effectiveness was assessed primarily by the best overall response. Patients The study enrolled patients with RRMM who received ELd therapy between November 18, 2016, and June 18, 2017. The safety and effectiveness analysis sets included 831 and 755 patients, respectively. Results In the safety analysis set, patients received a median (range) of 12 (1-40) elotuzumab administrations over 108 (1-728) days of treatment. The relative dose intensity of elotuzumab was ≥90% in 74.1% of patients. ADRs and serious ADRs were reported in 41.2% and 15.2% of the patients, respectively. The most common ADR was infection (12.0%), followed by lymphocytopenia (10.1%), infusion reactions (7.5%), secondary malignancies (e.g., gastric cancer and pancreatic carcinoma), cataracts, and interstitial lung disease (0.2% each). While most patients with ADRs recovered, 71 discontinued treatment, and 14 deaths were reported. The presence of comorbidities, particularly cardiovascular disorders, significantly affected the safety. The overall response rate was 41.1%. Conclusion This all-case post-marketing surveillance study showed that ELd had an acceptable tolerability profile and promising clinical activity in Japanese patients with RRMM.
The purpose of this study was to clarify whether coronary flow velocity reserve (CFVR), evaluated by adenosine 5'-triphosphate-induced hyperemia, is improved by single low-density lipoprotein (LDL) apheresis. Lipid lowering therapy is known to improve endothelium-dependent vasodilatation in forearm or coronary resistant vessels. However, few reports have studied the effect of acute LDL reduction on CFVR.Seven patients with familial hypercholesterolemia and significant coronary stenosis except in the left anterior descending artery (LAD) were enrolled in this study. Coronary flow velocity reserve was estimated before and after LDL apheresis using transthoracic Doppler echocardiography (TTDE), which detects the flow velocity at the distal site of the LAD. Although the averaged diastolic peak velocity (ADPV) during ATP-induced hyperemia was similar before and after LDL apheresis, the ADPV at baseline decreased from 30.69 to 25.56 cm/s, resulting in an increased CFVR from 1.78 to 2.10 (P < 0.001). Plasma bradykinin and 6 keto PGF1alpha increased while fibrinogen and plasma viscosity decreased after apheresis. Single LDL apheresis improves CFVR according to TTDE analysis because of the decreasing ADPV at baseline, which is thought to be induced by epicardial coronary artery dilatation and improved microvessel function. This is the result of various factors, such as changes in plasma LDL cholesterol, bradykinin and PGI2 levels with LDL apheresis.
We present the case of a 75-year-old female who developed restenosis after the deployment of kissing sirolimus-eluting stents at the left main coronary artery (LMCA) bifurcation. Restenosis occurred at the left circumflex (LCx) artery ostium, where a stent deployed from the LMCA to the LCx arteries overlapped another stent deployed from the LMCA to the left anterior descending (LAD) artery. We investigated the stent expansion and deformation after kissing stent implantation using a phantom three-dimensional model depicting a LMCA bifurcation. Stent overlap was detected at the distal LMCA whether the LAD stent was positioned over the left circumflex (LCx) stent or vice versa. Stent overlap created a gap beneath the overlapped portion of the stent. Thus, we found that kissing stent implantation using different-sized stents produced compression of the LCx stent at the distal LMCA. Incomplete stent apposition caused by stent overlap and stent deformation is thought to be the main mechanism for restenosis after kissing stent implantation procedures.
A 71-year-old man with paroxysmal atrial fibrillation who had a previous anterior myocardial infarction exhibited granulocytopenia 8 days following the administration of oral sustainedrelease procainamide (750mg/day). The plasma concentrations of procainamide and Nacetyl procainamide were at subtherapeutic levels. Discontinuation of procainamide led to complete recovery. A bone marrow aspiration showed slight hypoplasia with normocellular marrow. Lupus erythematosus (LE) and antinuclear antibody (ANA) tests were negative. The frequency and relationship of granulocytopenia caused by sustainedrelease procainamide in patients with tachyarrhythmias are briefly discussed, and prior reported cases are reviewed. Precautionary measures for the early recognition of this grave hazard in exposed patients are advocated. The physician should be aware of this complication before initiating treatment with this drug.
