The objective of this study was to examine healthcare resource utilization (HRU) and costs associated with switching to another tumor necrosis factor alpha inhibitor (TNFi) therapy versus a non-TNFi therapy among patients with rheumatoid arthritis (RA) discontinuing use of an initial TNFi biologic therapy.
Patients with ≥2 RA diagnoses who used ≥1 TNFi on or after their initial RA diagnosis were identified in a US employer-based insurance claims database. Patients were selected based on ≥1 claim of another TNFi or a non-TNFi biologic therapy (occurring after 2010, and within 30 days before to 60 days after discontinuation of the initial TNFi), and continuous insurance ≥6 months before (baseline period) and ≥12 months after the switch date (study period). Patient demographic and clinical characteristics were measured during the baseline period. All-cause and RA-related HRU and costs were analyzed during the 12-month study period using multivariable regression analysis controlling for baseline characteristics and selected comorbidities.
Of the 1577 patients with RA that switched therapies, 1169 patients used another TNFi and 408 patients used a non-TNFi biologic. The most commonly used initial TNFi treatments were etanercept (50%) and adalimumab (34%) among the TNFi cohort, and infliximab (39%) and etanercept (28%) among the non-TNFi cohort. The TNFi cohort had significantly fewer outpatient visits [all-cause: 23.01 vs. 29.77 visits/patient/year; adjusted incidence rate ratio (IRR) = 0.78, P < 0.001; RA-related: 7.42 vs. 13.58; adjusted IRR = 0.58, P < 0.001] and rheumatologist visits (all-cause: 4.01 vs. 6.81; adjusted IRR = 0.66, P < 0.001; RA-related: 3.23 vs. 6.40; adjusted IRR = 0.58, P < 0.001) than the non-TNFi cohort. All-cause total costs were significantly lower for patients who switched to another TNFi instead of a non-TNFi therapy ($36,932 vs. $44,566; adjusted difference = $7045, P < 0.01), as were total RA-related costs ($26,973 vs. $31,735; adjusted difference = $4904, P < 0.01).
Adult patients with RA discontinuing TNFi therapy who switched to an alternative TNFi incurred lower healthcare costs than patients who switched to a non-TNFi biologic.
AbbVie, Inc.

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Somatic mutations in the tumor suppressor gene p53 occur in more than half of all human cancers. Rare germline mutations result in the Li-Fraumeni cancer family syndrome. In this issue ofGenes&Development, Jennis and colleagues (pp. 918-930) use an elegant mouse model to examine the affect of a polymorphism, P47S (rs1800371), in the N terminus of p53 that is found in Africans as well as more than a million African Americans. Remarkably, the single nucleotide change causes the mice to be substantially tumor-prone compared with littermates, suggesting that this allele causes an increased risk of developing cancer. The defect in p53 function is traced to a restriction in downstream gene regulation that reduces cell death in response to stress.
© 2016 Lane; Published by Cold Spring Harbor Laboratory Press.

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Current methods to determine cellular cytotoxicity in vitro are hampered by background signals that are caused by auto-fluorescent target and effector cells and by non-specific cell death. We combined and adjusted existing cell viability assays to develop a method that allows for highly reproducible, accurate, single cell analysis by high throughput FACS, in which non-specific cell death is corrected for. In this assay the number of living, calcein AM labeled cells that are green fluorescent are quantified by adding a fixed number of unlabeled calibration beads to the analysis. Using this modified FACS calcein AM retention method, we found EC50 values to be highly reproducible and considerably lower compared to EC50 values obtained by conventional assays, displaying the high sensitivity of this assay.
Copyright © 2015. Published by Elsevier B.V.

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Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases.
Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial.
Published by Elsevier Inc.

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On April 16, 2016 Adaptive Biotechnologies, the leader in combining next generation sequencing (NGS) and expert bioinformatics to profile T- and B-cell receptors of the adaptive immune system, along with its collaborators from institutions around the world, will present data demonstrating how Adaptive’s immunosequencing platform can be used as a novel oncology diagnostic to accurately and reliably quantify the density and clonality of Tumor Infiltrating Lymphocytes (TILs) to assess disease prognosis and response to therapy (Press release, Adaptive Biotechnologies, APR 16, 2016, View Source [SID:1234511008]). Two oral presentations and eight posters will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 16-20, 2016, in New Orleans, Louisiana.

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Notably, many of the data to be presented explore the relevance of the immune repertoire in the blood as well as in the tumor tissue. The potential to identify blood-based immune molecular biomarkers of response to the growing class of immunomodulatory drugs may offer clinicians a more accessible sample source for widespread benefit to patients across many tumor types.

Select data presentations of interest include:

Dr. Robert Prins, et al. from UCLA will present data showing that in patients with glioblastoma undergoing immunotherapy, immunosequencing identified a potential biomarker of response and overall survival (Abstract 767).
Dr. Padmanee Sharma, et al. from MD Anderson Cancer Center will present data from a prostate cancer patient cohort receiving ipilumumab and androgen deprivation therapy correlating immune profiling data with adverse events which led to discovery of a potential predictive biomarker of patients who are at risk of grade 3 toxicities. (Abstract 1402).
Dr. Rebecca Gardner, et al. from Seattle Children’s Research Institute will present data on children with acute lymphoblastic leukemia (ALL) treated with a CART-19 therapy showing that high-throughput sequencing of patient samples had significantly greater sensitivity in detecting minimal residual disease (MRD) compared with samples analyzed by flow cytometry. Furthermore, in these patients, monitoring disease status by peripheral blood sampling is often more informative and far less invasive than bone marrow sampling. (Abstract 4893).
"These data being presented at AACR (Free AACR Whitepaper) demonstrate the utility of immunosequencing in both tissue and blood samples as a critical component in guiding clinicians’ approach to managing and treating cancer," said Harlan Robins, Chief Scientific Officer and Co-Founder of Adaptive Biotechnologies. "Ultimately incorporating immunosequencing into a potential blood-based biomarker for use in the clinic may help enhance the diagnosis, prognosis and monitoring of disease in cancer patients."

Representatives from Adaptive Biotechnologies will be exhibiting at AACR (Free AACR Whitepaper) booth #2530 to answer questions about their proprietary, transformative immunosequencing technology.

Oral Presentations:
Abstract #847: Molecular characterization of breast tumor T-cell infiltration in exome datasets
Date and Time: Sunday, Apr 17, 2016, 4:35 PM – 4:50 PM
Location: Room 243, Morial Convention Center
Presenter: Ricardo Armisen, Universidad de Chile, Santiago, Chile

Abstract #4362: T cell repertoire diversification is associated with immune related toxicities following immune checkpoint inhibition in metastatic cancer patients
Date and Time: Tuesday, Apr 19, 2016, 3:50 PM – 4:05 PM
Location: New Orleans Theater C, Morial Convention Center
Presenter: Lawrence Fong, University of California, San Francisco

Posters:

Abstract #767: TCR sequencing can identify and track tumor-specific T cell populations and is a predictive biomarker of response to DC vaccination in glioblastoma patients
Date and Time: Sunday, Apr 17, 2016, 1:00 PM – 5:00 PM
Location: Section 33, Poster Board #26
Author: Robert Prins, et al., University of California, Los Angeles

Abstract #1402: Exploratory biomarkers that predict for clinical outcomes in a Phase II trial with ipilimumab plus finite androgen deprivation therapy for metastatic non-castrate prostate cancer
Date and Time: Monday, Apr 18, 2016, 8:00 AM -12:00 PM
Location: Section 22, Poster Board #3
Author: Padmanee Sharma, et al., The University of Texas MD Anderson Cancer Center

Abstract #1405: Vesigenurtacel-L stimulates tumor infiltration of unique polyclonal T cell clones in non-muscle invasive bladder cancer patients
Date and Time: Monday, Apr 18, 2016, 8:00 AM -12:00 PM
Location: Section 22, Poster Board #6
Author: Melissa Price, et al., Heat Biologics, Inc., Durham, NC

Abstract #2392: Genomic and immune heterogeneity in synchronous melanoma metastases is associated with differential tumor growth and response to therapy
Date and Time: Monday, Apr 18, 2016, 1:00 PM -5:00 PM
Location: Section 28, Poster Board #22
Author: Jennifer A. Wargo, et al., MD Anderson Cancer Center, Houston, TX

Abstract #4159: Characterization of the T-cell receptor (TCR) repertoire in extensive disease small cell lung cancer (ED SCLC)
Date and Time: Tuesday, Apr 19, 2016, 1:00 PM – 5:00 PM
Location: Section 31, Poster board #26
Author: Cory Batenchuk, et al., Bristol-Myers Squibb, NJ

Abstract #4903: Multimodal therapy with a potent vaccine, metronomic cyclophosphamide and anti-PD-1 enhances immunotherapy of advanced tumors by increasing activation and clonal expansion of tumor infiltrating T cells
Date and Time: Wednesday, Apr 20, 2016, 7:30 AM – 11:00 AM
Location: Section 23, Poster board #14
Author: Genevieve Weir, et al., Immunovaccine, Inc., Halifax, NS, Canada

Abstract #4893: Molecular detection of ALL in the peripheral blood is more sensitive than flow cytometric analysis of the bone marrow in patients with treatment-related hypocellularity
Date and Time: Wednesday, Apr 20, 2016, 8:00 AM -12:00 PM
Location: Section 23, Poster board #4
Author: Rebecca Gardner, et al., Seattle Children’s Research Institute, Seattle, WA

Abstract #4897: First evidence of changes in the TCRβ repertoire from a cutaneous melanoma patient immunized with the CSF-470 vaccine.
Date and Time: Wednesday, Apr 20, 2016, 8:00 AM -12:00 PM
Location: Section 23, Poster board #8
Author: José Mordoh, et al., Centro de Investigaciones Oncológicas-Fundación Cáncer, Ciudad Autónoma de Buenos Aires, Argentina

About the immunoSEQ Platform
Adaptive’s immunoSEQ Platform helps researchers make discoveries in areas such as oncology, autoimmune disorders, infectious diseases and basic immunology. The immunoSEQ Assays can identify millions of T- and B-cell receptors from a single sample in exquisite detail. Offered as a Service or Kit, immunoSEQ Assays provide quantitative, reproducible sequencing results along with access to powerful, easy-to-use analysis tools. The immunoSEQ Assays are for research use only and are not for use in diagnostic procedures.

About Minimal Residual Disease
Minimal residual disease (MRD) refers to cancer cells that may remain in the body of a person with lymphoid cancer after treatment. These cells are present at levels undetectable by traditional microscopic examination (also called morphologic examination) of blood, bone marrow or a lymph node biopsy. Sensitive molecular technologies, such as the next-generation sequencing utilized by Adaptive’s clonoSEQ MRD Test, are needed for reliable detection of very low levels of MRD. Learn more at knowMRD.com.

About the clonoSEQ Process
Adaptive’s clonoSEQ Process enables physicians to utilize sequencing-based minimal residual disease (MRD) detection as an aid to clinical decision making for patients with lymphoid cancers (blood cancers). With its ability to detect cancer cells at a level as low as one per one million white blood cells, the clonoSEQ MRD Test is one to two orders of magnitude more sensitive than the other methods of MRD detection, such as ASO-PCR and flow cytometry.