Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues. The reader precision, repeatability and intermediate precision, interlaboratory reproducibility, and the effectiveness of pathologist training on the assessment of PD-L1 staining on both TC and IC were evaluated. We detail the analytical validation of the VENTANA PD-L1 (SP142) Assay for PD-L1 expression in NSCLC and UC tissues and show that the assay reliably evaluated staining on both TC and IC across multiple expression levels/clinical cut-offs. The reader precision showed high overall agreement when compared with consensus scores. In addition, pathologists met the predefined training criteria (≥85.0% overall percent agreement) for the assessment of PD-L1 expression in NSCLC and UC tissues with an average overall percent agreement ≥95.0%. The assay evaluates PD-L1 staining on both cell types and is robust and precise. In addition, it can help to identify those patients who may benefit the most from treatment with atezolizumab, although treatment benefit has been demonstrated in an all-comer NSCLC and UC patient population.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

The objective was to use the United States Renal Data System (USRDS) to quantify the relationship between immunosuppressant therapy (IST) adherence and risk of graft failure among adult renal transplant recipients (RTRs). A secondary objective was to examine the relationship among select patient characteristics and IST adherence. The study sample included adult RTRs who: received primary transplant between January 1, 1999 and December 31, 2005; experienced graft survival for at least 12 months post-transplant and had at least 12 months of data in the USRDS; utilized Medicare coverage for IST; and were prescribed cyclosporine or tacrolimus. IST adherence was measured by medication possession ratio (MPR). Pearson chi-square tests were used to examine associations between patient characteristics and MPR quartiles. Cox proportional hazards regression was used to assess relationships among time to graft failure, MPR, and patient characteristics. Thirty-one thousand nine hundred and thirteen RTRs met inclusion criteria. Older age, female gender, white race, deceased donors, and tacrolimus were associated with greater adherence (p < 0.001). Cox proportional hazard modeling indicated greater adherence, white race, and having a living donor were significantly associated with longer graft survival (p < 0.05). Future prospective studies should further examine the clinical significance of IST nonadherence as it relates to graft failure.

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Background: Immune checkpoint inhibitors (CPIs) are now an accepted standard of care along the treatment algorithm for advanced non-small cell lung cancer (NSCLC). PD-L1 expression using 22C3 immunohistochemistry (IHC) help determine the line of therapy in which CPI are used. Previous studies demonstrated that PD-L1 expression is comparable on cytology versus solid biopsy/histology specimens. We assess the clinical outcomes between patients with PD-L1 expression 50% (high positive) tested using cytology versus histology specimens. Method: This retrospective cohort study includes specimens processed between . Patients were included in the study if they were seen by a medical oncologist for consideration of systemic treatment for advanced NSCLC. Clinical characteristics were extracted from electronic medical records. Overall survival (OS) was defined as time from diagnosis of advanced NSCLC to death and compared by method of PD-L1 analysis (cytology versus histology), adjusting for age, ECOG, weight loss, and receipt of palliative intent radiotherapy, targeted therapy, and CPI. Result: 148 (30.8%) of 481 samples tested 50% for PD-L1 expression. Amongst those, 32 and 37 patients fulfilled eligibility criteria with cytology and histology samples respectively. Baseline characteristics of the two groups are comparable in age, gender, ECOG, histological subtype, and receipt of CPIs. The cytology group had a significantly higher number of patients with baseline pleural effusion (10 vs 4 patients, p¼0.035) and receipt of any systemic therapy (28 vs 22 patients, p¼0.009). The histology group received more palliative intent radiation (24 vs 13, p¼0.044). There was no difference in OS between the cytology and histology groups. Median OS in the cytology group was 11.9 versus 8.0 months in the histology group; adjusted HR 0.98 (95% CI 0.43-2.26). Amongst patients who received systemic therapy, survival was longer if patients were exposed to CPI during their course of treatment regardless of cytology or histology groups; adjusted HR 0.45 (95% CI 0.22 e 0.90). Conclusion: In advanced NSCLC, CPI treatment guided by specimens analyzed by cytology versus histology were equivalent in survival. Regardless of sample source, patients exposed to CPI in any line of therapy had significantly longer survival than patients without exposure to CPI amongst patients testing high positive for PD-L1. Ongoing analyses are comparing clinical outcomes in patients with other expressions of PD-L1.Background: Fine needle aspirations (FNA) are a common type of sample that is obtained for diagnostic purposes in small cell lung cancer (SCLC) patients due to its relatively less invasive nature. Several delta-like protein 3 (DLL3) therapies that target DLL3 in SCLC are under development. We recently developed an immunohistochemistry assay utilizing a rabbit monoclonal antibody that can be used to identify patients that may potentially respond to DLL3 targeted therapies. Due to the high prevalence of FNA samples in SCLC, the robustness of the VENTANA DLL3 (...