Efficacy and Toxicity Profile of Carfilzomib-Based Regimens for Treatment of Newly Diagnosed Multiple Myeloma: A Systematic Review.

Carfilzomib (CFZ) is a proteasome inhibitor currently approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Multiple trials are ongoing to evaluate its efficacy and safety in newly diagnosed multiple myeloma (NDMM). The use of CFZ-based two- or three-drug combination regimens as induction for the management of NDMM is an emerging approach. CFZ-based regimens include combinations of immunomodulators, alkylating agents, and monoclonal antibodies along with dexamethasone. In this review, we assess the efficacy and toxicity of CFZ-based regimens in NDMM. We reviewed a total of 27 studies (n=4538 patients) with overall response rates (ORR) ranging between 80% and 100%. Studies evaluating the combination of CFZ with daratumumab reported an ORR of approximately 100%. Achievement of minimal residual disease (MRD) negativity, measured by multi-parameter flow cytometry (MPFC), ranged between 60% and 95% in 4 (n=251) out of 6 studies that measured MRD-negativity. The interim results of the ENDURANCE trial failed to show superior efficacy and progression-free survival (PFS) of carfilzomib-lenalidomide when compared to bortezomib-lenalidomide combination, albeit with a lower incidence of neuropathy. Hematological toxicity was the most common adverse event observed with these regimens, and the most common non-hematological adverse events were related to cardiovascular and electrolyte disturbances. We need to further evaluate the role of CFZ in NDMM by conducting more Phase III trials with different combinations.

Fast and low loss flexoelectro-optic liquid crystal phase modulator with a chiral nematic reflector.

In this paper, we demonstrate a flexoelectro-optic liquid crystal phase-only device that uses a chiral nematic reflector to achieve full 2π phase modulation. This configuration is found to be very tolerant to imperfections in the chiral nematic reflector provided that the flexoelectro-optic LC layer fulfils the half-wave condition. Encouragingly, the modulation in the phase, which operates at kHz frame rates, is also accompanied by low amplitude modulation. The configuration demonstrated herein is particularly promising for the development of next-generation liquid crystal on silicon spatial light modulators.

Natural History and Predictors of Parastomal Hernia after Robot-Assisted Radical Cystectomy and Ileal Conduit Urinary Diversion.

PURPOSE: We investigated the prevalence of and variables associated with parastomal hernia and its outcomes after robot-assisted radical cystectomy and ileal conduit creation for bladder cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent robot-assisted radical cystectomy at our institution. Parastomal hernia was defined as the protrusion of abdominal contents through the stomal defect in the abdominal wall on cross-sectional imaging. Parastomal hernia was further described in terms of patient and hernia characteristics, symptoms, management and outcomes. The Kaplan-Meier method was used to determine time to parastomal hernia and time to surgery. Multivariate stepwise logistic regression was done to evaluate variables associated with parastomal hernia. RESULTS: A total of 383 patients underwent robot-assisted radical cystectomy and ileal conduit creation. Of the patients 75 (20%) had parastomal hernia, which was symptomatic in 23 (31%), and 11 (15%) underwent treatment. Median time to parastomal hernia was 13 months (IQR 9-22). Parastomal hernia developed in 9%, 23% and 32% of cases at 1, 2 and 3 years, respectively. Patients with parastomal hernia had a significantly higher body mass index (30 vs 28 kg/m2, p = 0.02), longer overall operative time (357 vs 340 minutes, p = 0.01) and greater blood loss (325 vs 250 ml, p = 0.04). On multivariate analysis operative time (OR 1.25, 95% CI 1.21-3.90, p <0.001), a fascial defect 30 mm or greater (OR 5.23, 95% CI 2.32-11.8, p <0.001) and a lower postoperative estimated glomerular filtration rate (OR 2.17, 95% CI 1.21-3.90, p = 0.01) were significantly associated with parastomal hernia. CONCLUSIONS: Symptoms develop in approximately a third of patients with parastomal hernia and 15% will require surgery. The risk of parastomal hernia plateaued after postoperative year 3. Longer operative time, a larger fascial defect and lower postoperative kidney function were associated with parastomal hernia.

Natural History, Predictors and Management of Ureteroenteric Strictures after Robot Assisted Radical Cystectomy.

PURPOSE: Ureteroenteric strictures represent the most common complication requiring reoperation after radical cystectomy. We investigated the prevalence, outcomes, predictors and management of ureteroenteric strictures. MATERIALS AND METHODS: We retrospectively reviewed our quality assurance, robot assisted radical cystectomy database to identify patients in whom ureteroenteric strictures developed. Data were reviewed for demographics, perioperative outcomes and ureteroenteric stricture characteristics. The Kaplan-Meier method was used to calculate time to ureteroenteric stricture and multivariable stepwise regression was done to evaluate predictors of ureteroenteric strictures. RESULTS: Ureteroenteric strictures developed in 12%, 16% and 19% of 51 patients (13%) at 1, 3 and 5 years after robot assisted radical cystectomy, respectively. All patients were initially treated endoscopically or percutaneously, including 57% treated only endoscopically or percutaneously and 43% who required surgery, which was open repair in 6 and robot assisted repair in 16. At a median followup of 23 months 33 patients (65%) were free of disease, including 13 after endoscopic or percutaneous treatment, 15 after robot assisted repair and 5 after open revision. Open and robot assisted revisions showed comparable perioperative outcomes. On multivariable analysis the predictors of ureteroenteric anastomotic strictures were body mass index (OR 1.07, 95% CI 1.01-1.13, p = 0.02), intracorporeal urinary diversion (OR 3.28, 95% CI 1.41-7.61, p = 0.006), length of the right resected ureter (OR 0.66, 95% CI 0.50-0.88, p = 0.004), estimated glomerular filtration rate 30 days after assisted radical cystectomy (OR 0.85, 95% CI 0.74-0.98, p = 0.03), urinary tract infection (OR 2.68, 95% CI 1.31-5.49, p = 0.007) and leakage (OR 3.85, 95% CI 1.05-14.1, p = 0.04). Male gender (OR 0.19, 95% CI 0.04-0.96, p = 0.04) and higher body mass index (OR 0.85, 95% CI 0.72-0.996, p = 0.05) were associated with lower odds of successful endoscopic management. CONCLUSIONS: Multiple modifiable factors were associated with ureteroenteric anastomotic strictures following robot assisted radical cystectomy. Surgical revision can provide a definitive management with comparable outcomes for open and robotic repairs.