As research focus in oncology has recently shifted from oral targeted therapy to immunomodulation, the era of successful drug development in bladder cancer has just begun. This has led to unprecedented approval of five immunotherapeutic agents by regulatory agencies for metastatic bladder cancer within a span of 12 months. With an initial triumph of anti-programmed cell death-1 (anti-PD-1) and anti-programmed cell death ligand-1 (anti-PDL-1) drugs, ongoing efforts are aimed at identification and validation of new druggable immune targets to consolidate the initial gains. In this paper, we review the role of immunotherapy in the treatment of bladder cancer as well as the various emerging immunotherapeutic agents and their possible use in bladder cancer.
BackgroundBehçet’s disease is a progressive diffuse inflammatory vasculitis characterized by recurrent oral and genital ulceration and ocular inflammation. Cardiac involvement is a rare but well-documented manifestation of Behçet’s disease. Complete heart block in non-Caucasian populations has been reported previously; however, in this report, we describe a unique case of complete heart block in a Caucasian woman with Behçet’s disease.Case presentationA 48-year-old Caucasian woman presented to our hospital with symptomatic complete heart block requiring a pacemaker implant on a background of recurrent oral and genital ulcers and oligoarthritis of 10 months’ duration. She also had a history of recurrent diarrhea with a single episode of ocular inflammation in the recent past. She had no evidence of cardiac ischemia, and her autoimmune antibodies were within normal ranges. She was diagnosed with Behçet’s disease according to international study group criteria and was commenced on prednisolone and sulfasalazine, to which she responded very well.ConclusionsCardiac complications should be considered when making a diagnosis of Behçet’s disease, even in Caucasian patients. While mucocutaneous ulceration is indeed the most common manifestation of Behçet’s disease, cardiovascular involvement tends to cause the most morbidity and mortality.
4530 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: Ten systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value. Selected variables were then analyzed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and albumin categorized as < vs > 30 g/dL were found as the most meaningful independent predictors of OS and used to build the GIPI nomogram. Nomogram-based lowest (l), mid-low, mid-high and highest (h) risk quartiles were associated with median(m)OS of 14.9, 7.1, 5.6 and 2.1 months (mos), respectively [HR of l vs h 4.94, p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR >6, CRP >15 mg/L, albumin <30 g/dL (n: 29) had a mOS of 3.9 mos vs 14.2 mos of pts with no risk factor (n: 28) (HR 2.48, p 0.001). Conclusions: GIPI, combining NLR, CRP and Albumin, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second-line ICIs. Its implementation in correlation with PD-L1 expression in the present cohort is ongoing. GIPI merits validation in independent cohorts and prospective clinical trials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.