Selinexor for the treatment of patients with relapsed or refractory multiple myeloma.

OBJECTIVE: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. DATA SOURCE: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. DATA SUMMARY: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%. CONCLUSION: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

Acute Kidney Injury in Transcatheter Aortic Valve Replacement.

Introduction Transcatheter aortic valve replacement (TAVR) has been established as a standard of care for patients with severe aortic stenosis. We aim to study the predictors of acute kidney injury (AKI) after TAVR from a contemporary analysis using the National Inpatient Sample (NIS) database. Methods We performed a national analysis using the NIS database to evaluate predictors of acute kidney injury (AKI) after TAVR. Our study period was from 2015 to 2018, and we identified TAVR patients in all procedure fields. Patients aged less than 18 years were excluded from the study. Results We report data of 173,760 TAVR patients, of which 20,045 (11.5%) had AKI and 153,715 (88.4%) did not. There were three principal findings of our study. First, mortality was higher in patients with AKI compared to patients who did not have AKI (8% vs. 0.8%; p<0.01). Second, patients with chronic kidney disease, weight loss, liver disease, congestive heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, metastatic cancer, and peripheral vascular disease had higher adjusted odds of AKI. Third, length of stay and cost of stay were significantly higher in patients who had AKI during the index admission.  Conclusion Patients with AKI had higher in-hospital mortality. We also report that at baseline, chronic kidney disease, weight loss, liver disease, congestive heart failure, cerebrovascular disease, chronic obstructive pulmonary disease, metastatic cancer, and peripheral vascular disease were important predictors of AKI in patients after TAVR. Length of stay and cost of stay were higher with AKI, which result in higher burden on the health care system due to increased resource utilization.