899 Population coverage of HLA-A*02:01, *02:05, *02:06 across selected cancer types in the United States

BackgroundGSK is investigating an autologous TCR T-cell therapy for solid tumors that recognizes the cancer testis antigen, NY-ESO-1, presented on the cancer cell surface by specific HLA-A*02 sub-types. The aim of this study was to estimate the number of patients in the US in 2020 with HLA-A*02 genotype subtypes HLA-A*02:01, 02:05, 02:06 across selected cancer types (invasive lung, ovarian, gastric, esophageal, invasive and in-situ bladder and multiple myeloma), accounting for racial variation.MethodsThis study was carried out in three parts utilizing three national datasets.1. The prevalence of each cancer type was estimated by race utilizing prevalence rates from US Surveillance, Epidemiology, and End Results (SEER) 1975–2018 data.1 2. The US population coverage for the specific HLA-A*02 subtype (%) by race in 2020, was estimated utilizing Hardy Weinberg Principles and allele frequencies extracted from the allele frequency net database (US National Marrow Donor Program (NMDP) population only).2 3. The estimated population coverage for the specific HLA-A*02 subtype expression (%) by cancer subtype, was calculated using US Census (2019) data.3 For the purpose of this analyses, single race population estimates were used. Race was categorized as ‘White’, ‘Black’, ‘Asian/Pacific Islander’, ‘Native American’ and ‘Other’. The Hispanic population was included as a proportion of each category, where appropriate. Limitations include the seven assumptions underlying Hardy-Weinberg equilibrium, which were met, and the assumption that the NMDP, SEER and US Census data are reflective of the US population. Predictive and prognostic clinical characteristics including histological subtypes were not accounted for in this analysis.ResultsAcross selected cancer types, the most prevalent race category was White, reflecting the racial distribution of the US (table 1). Of these cancer types, multiple myeloma and invasive gastric cancer are represented by the lowest proportion of White patients and the highest proportion of Black patients. Results of the HLA sub-type distribution by race are presented in the table below. The overall proportion of patients who are HLA-A*02:01, *02:05 or *02:06 positive is estimated to be between 41.7% (multiple myeloma) and 45.8% (invasive and in-situ bladder) in the US accounting for the racial variations in each cancer type of interest.Abstract 899 Table 1Proportion of patients who are HLA-A*02:01, *02:05, or *02:06 positive by race and cancer subtypeConclusionsThe proportion of patients with specific HLA-A*02 subtypes is similar across selected cancers, accounting for racial variation in the US. Racial variation by cancer type is an important consideration when estimating the size of eligible populations for T-cell therapies requiring specific HLA-A*02 histocompatibility.AcknowledgementsFundingGlaxoSmithKlineReferencesHowlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2018, National Cancer Institute. Bethesda, MD, [https://seer.cancer.gov/csr/1975_2018/], based on November 2020 SEER data submission, posted to the SEER web site, April 2021 (Accessed July 2021).Gonzalez-Galarza FF, McCabe A, Santos EJ, Jones J, Takeshita LY, Ortega-Rivera ND, Del Cid-Pavon GM, Ramsbottom K, Ghattaoraya GS, Alfirevic A, Middleton D, Jones AR. Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools. Nucleic Acids Res 2020;48:D783–8.U S Census Bureau (2011). ACS demographic and housing estimates. [https://data.census.gov/cedsci/table?q=United%20States&g=0100000US&tid=ACSDP1Y2017.DP05&vintage=2017&layer=state&cid=DP05_0001E] (Accessed July 2021).

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Prevalence and Outcome of COVID-19 Infection in Cancer Patients: A National Veterans Affairs Study

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa159 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nathanael R Fillmore ◽

Jennifer La ◽

Raphael E Szalat ◽

David P Tuck ◽

Vinh Nguyen ◽

...

Keyword(s):

African American ◽

Cancer Patients ◽

Hematologic Malignancy ◽

Statistical Tests ◽

Veterans Affairs ◽

Attributable Mortality ◽

Cancer Type ◽

The Us ◽

Charlson Comorbidity Score ◽

Cancer Types

Abstract Background Emerging data suggest variability in susceptibility and outcome to coronavirus disease 2019 (COVID-19) infection. Identifying risk factors associated with infection and outcomes in cancer patients is necessary to develop healthcare recommendations. Methods We analyzed electronic health records of the US Veterans Affairs Healthcare System and assessed the prevalence of COVID-19 infection in cancer patients. We evaluated the proportion of cancer patients tested for COVID-19 who were positive, as well as outcome attributable to COVID-19, and stratified by clinical characteristics including demographics, comorbidities, cancer treatment, and cancer type. All statistical tests are 2-sided. Results Of 22 914 cancer patients tested for COVID-19, 1794 (7.8%) were positive. The prevalence of COVID-19 was similar across age. Higher prevalence was observed in African American (15.0%) compared with White (5.5%; P < .001) and in patients with hematologic malignancy compared with those with solid tumors (10.9% vs 7.8%; P < .001). Conversely, prevalence was lower in current smokers and patients who recently received cancer therapy (<6 months). The COVID-19–attributable mortality was 10.9%. Higher attributable mortality rates were observed in older patients, those with higher Charlson comorbidity score, and in certain cancer types. Recent (<6 months) or past treatment did not influence attributable mortality. Importantly, African American patients had 3.5-fold higher COVID-19–attributable hospitalization; however, they had similar attributable mortality as White patients. Conclusion Preexistence of cancer affects both susceptibility to COVID-19 infection and eventual outcome. The overall COVID-19–attributable mortality in cancer patients is affected by age, comorbidity, and specific cancer types; however, race or recent treatment including immunotherapy do not impact outcome.

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Prevalence and outcome of Covid-19 infection in cancer patients: a national VA study

10.1101/2020.08.21.20177923 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nathanael R Fillmore ◽

Jennifer La ◽

Raphael E Szalat ◽

David P Tuck ◽

Vinh Nguyen ◽

...

Keyword(s):

Cancer Patients ◽

Hematologic Malignancy ◽

Current Smoker ◽

Attributable Mortality ◽

Veterans Administration ◽

Cancer Type ◽

Morbidity Score ◽

Co Morbidity ◽

The Us ◽

Cancer Types

Background: Emerging data suggest variability in susceptibility and outcome to Covid-19 infection. Identifying the risk-factors associated with infection and outcomes in cancer patients is necessary to develop healthcare recommendations. Methods: We analyzed electronic health records of the US National Veterans Administration healthcare system and assessed the prevalence of Covid-19 infection in cancer patients. We evaluated the proportion of cancer patients tested for Covid-19 and their confirmed positivity, with clinical characteristics, and outcome, and stratified by demographics, comorbidities, cancer treatment and cancer type. Results: Of 22914 cancer patients tested for Covid-19, 1794 (7.8%) were positive. The prevalence of Covid-19 was similar across all ages. Higher prevalence was observed in African-American (AA) (15%) compared to white (5.5%; P<.001), in Hispanic vs non-Hispanic population and in patients with hematologic malignancy compared to those with solid tumors (10.9% vs 7.7%; P<.001). Conversely, prevalence was lower in current smoker patients, patients with other co-morbidities and having recently received cancer therapy (<6 months). The Covid-19 attributable mortality was 10.9%. Highest mortality rates were observed in older patients, those with renal dysfunction, higher Charlson co-morbidity score and with certain cancer types. Recent (<6 months) or past treatment did not influence mortality. Importantly, AA patients had 3.5-fold higher Covid-19 attributable hospitalization, however had similar mortality rate as white patients. Conclusion: Pre-existence of cancer affects both susceptibility to Covid-19 infection and eventual outcome. The overall Covid-19 attributable mortality in cancer patients is affected by age, co-morbidity and specific cancer types, however, race or recent treatment including immunotherapy does not impact outcome.

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Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma

Future Oncology ◽

10.2217/fon-2021-1090 ◽

2021 ◽

Author(s):

Larry D Anderson

Keyword(s):

Multiple Myeloma ◽

T Cell ◽

Cell Therapy ◽

T Cell Therapy ◽

Refractory Multiple Myeloma ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

The Us ◽

Us Fda

Idecabtagene vicleucel (ide-cel), a novel chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), has recently gained approval by the US FDA for relapsed and refractory multiple myeloma (RRMM) after multicenter trials have demonstrated unprecedented results in this difficult-to-treat subgroup of patients. As the first CAR T-cell product approved for myeloma, ide-cel is poised to become a practice-changing treatment option. This first-in-class therapeutic offers hope for more durable remissions, as well as better quality of life, following a single infusion in a group of patients that previously had little hope. This paper reviews the ide-cel product in terms of design, pharmacology, efficacy and toxicity as described in studies reported to date.

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Activity of the Histone Deacetylase (HDAC) Inhibitor PXD101 in Preclinical Studies and in a Phase I Study in Patients with Advanced Haematological Tumors.

Blood ◽

10.1182/blood.v106.11.3337.3337 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3337-3337 ◽

Cited By ~ 1

Author(s):

Peter Gimsing ◽

Frank Wu ◽

Xiaozhong Qian ◽

Michael Jeffers ◽

Lene Knudsen ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cell ◽

Adverse Events ◽

Phase I ◽

Histone Deacetylase ◽

Cell Lines ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Cell Leukaemia ◽

Cancer Types

Abstract Previous investigations have shown that the novel hydroxamate PXD101 potently inhibits the enzymatic activity of histone deacetylase (HDAC) at nanomolar concentration, and the growth of cancer cell lines derived from solid malignancies at low micromolar potency. We have now examined and present results showing the activity of PXD101 on > 20 cell lines corresponding to a variety of haematological cancer types including acute T-cell leukaemia, cutaneous T-cell lymphoma, anaplastic large T-cell lymphoma, mantle cell lymphoma, Burkitt’s lymphoma, diffuse large-cell lymphoma, plasma cell leukaemia and multiple myeloma (MM). Our data show that PXD101 strongly inhibits the growth of these cancer types at submicromolar potency. In addition, we will present in vitro data demonstrating that PXD101 efficiently inhibits the growth of doxorubicin-resistant leukemic cells, thereby supporting the possibility that this compound may be effective on drug-resistant haematological cancers. Finally, we will present results demonstrating that PXD101 used in combination with Velcade mediates greater growth-inhibition than does either drug used as monotherapy on a multiple myeloma cell line. These promising preclinical findings, taken together with previous results demonstrating the activity of PXD101 in a murine leukaemia animal model, support the evaluation of PXD101 for the treatment of haematological malignancies in a clinical setting. To this end, a Phase I trial using PXD101 in patients with advanced hematological tumors refractory to standard therapy was initiated. PXD101 is administered as a 30 minute i.v. infusion on days 1 to 5 of a 21 day cycle. Dose levels 600 mg/m2/d and 900 mg/m2/d have been examined (3 patients each) and recruitment to the dose level 1000 mg/m2/d is ongoing (5 patients to date). Patient characteristics are 8 males and 3 females with median age of 67 (range 58 – 73). Median number of prior therapies is 5 (range 4 – 7). Of the 11 patients enrolled to date, diagnoses were: MM (2), Non-Hodgkin’s lymphoma (5), CLL (4). Eleven patients have been treated with 1–8 cycles of therapy. Adverse events related to PXD101 treatment have mainly been grade 1–2. The most frequent adverse events were nausea (12/23 cycles), fatigue (9/23 treatment cycles), vomiting (8/23 cycles) and diarrhoea (7/23 cycles). Potential antineoplastic activity has been observed. One patient with MM had a possible tumor lysis syndrome with decrease in M-component, increasing urate and serum creatinine requiring dialysis. In addition, one patient with Richter transformation of CLL refractory to other treatments has now been in stable disease for > 6 months. We continue to accrue patients in this study, and updated data will be presented.

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Evaluating the confluence of oncology market trends and key levers to drive payment and delivery reform for treatment of multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.30_suppl.45 ◽

2014 ◽

Vol 32 (30_suppl) ◽

pp. 45-45

Author(s):

Jenna Waltersdorf ◽

Lauren G. Barnes ◽

Fauzea Hussain ◽

Kristi Mitchell

Keyword(s):

Multiple Myeloma ◽

National Level ◽

Quality Measures ◽

Treatment Costs ◽

Cancer Type ◽

Fee For Service ◽

National Guidelines ◽

Reform Initiatives ◽

Cancer Types ◽

Market Trends

45 Background: A multi-factorial focus on treatment costs and the incremental improvement in outcomes has accelerated interest in payment and delivery reform in oncology, specifically a shift from fee-for-service to fee-for-value. As the landscape continues to evolve, there are key levers that will accelerate reform for specific cancer types. Our objective was to examine how broad oncology market trends and key levers for multiple myeloma (MM) intersect to drive payment and delivery reform. Methods: We evaluated 18 oncology market trends, classified the pervasiveness of each as nascent, emerging, or widespread, and assessed trends for specificity to MM compared to other cancers. We then evaluated six key levers that, within the context of each trend, may ripen MM for payment and delivery reform. Levers included 1) national guidelines; 2) quality measures; 3) prevalence/incidence relative to other cancer types; 4) advanced imaging or other high-cost treatment expenditures; 5) drug/biologic contribution toward treatment costs; and 6) approved companion diagnostic(s). Results: While some guidelines exist to address treatment of MM, there are gaps in recommendations that do not address the full continuum of care to guide physician decision making, giving this lever low influence to drive reform. One measure for quality improvement has been used at a broad national level, giving this lever moderate influence on reform. Today, characteristics of MM that trigger key levers make MM an unlikely focus for widespread reform initiatives. Conclusions: Most oncology market trends are cancer-type agnostic, but trend pervasiveness and their confluence with key levers will dictate the shape of alternative payment models for changes to treatment delivery and reimbursement. By developing additional quality measures and addressing guideline gaps, stakeholders may further trigger two key levers to ripen MM for payment and delivery reform. Reform initiatives may be expedited as additional treatment options are introduced to the market, and as stakeholders work to influence key levers and evaluate the feasibility for and implementation new payment and delivery models for MM.

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Use of Mastectomy for Overdiagnosed Breast Cancer in the United States: Analysis of the SEER 9 Cancer Registries

Journal of Cancer Epidemiology ◽

10.1155/2019/5072506 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14

Author(s):

C. Harding ◽

F. Pompei ◽

D. Burmistrov ◽

R. Wilson

Keyword(s):

Breast Cancer ◽

Cancer Registries ◽

The United States ◽

Breast Cancers ◽

The Us ◽

Study Population ◽

Cancer Types ◽

Surgical Treatments ◽

Case Characteristics

Aim. We investigated use of mastectomy as treatment for early breast cancer in the US and applied the resulting information to estimate the minimum and maximum rates at which mastectomy could plausibly be undergone by patients with overdiagnosed breast cancer. Little is currently known about overtreatments undergone by overdiagnosed patients. Methods. In the US, screening is often recommended at ages ≥40. The study population was women age ≥40 diagnosed with breast cancer in the US SEER 9 cancer registries during 2013 (n=26,017). We evaluated first-course surgical treatments and their associations with case characteristics. Additionally, a model was developed to estimate probability of mastectomy conditional on observed case characteristics. The model was then applied to evaluate possible rates of mastectomy in overdiagnosed patients. To obtain minimum and maximum plausible rates of this overtreatment, we respectively assumed the cases that were least and most likely to be treated by mastectomy had been overdiagnosed. Results. Of women diagnosed with breast cancer at age ≥40 in 2013, 33.8% received mastectomy. Mastectomy was common for most investigated breast cancer types, including for the early breast cancers among which overdiagnosis is thought to be most widespread: mastectomy was undergone in 26.4% of in situ and 28.0% of AJCC stage-I cases. These rates are substantively higher than in many European nations. The probability-based model indicated that between >0% and <18% of the study population could plausibly have undergone mastectomy for overdiagnosed cancer. This range reduced depending on the overdiagnosis rate, shrinking to >0% and <7% if 10% of breast cancers were overdiagnosed and >3% and <15% if 30% were overdiagnosed. Conclusions. Screening-associated overtreatment by mastectomy is considerably less common than overdiagnosis itself but should not be assumed to be negligible. Screening can prompt or prevent mastectomy, and the balance of this harm-benefit tradeoff is currently unclear.

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Representativeness of Black Patients in Cancer Clinical Trials Sponsored by the National Cancer Institute Compared With Pharmaceutical Companies

JNCI Cancer Spectrum ◽

10.1093/jncics/pkaa034 ◽

2020 ◽

Vol 4 (4) ◽

Cited By ~ 4

Author(s):

Joseph M Unger ◽

Dawn L Hershman ◽

Raymond U Osarogiagbon ◽

Anirudh Gothwal ◽

Seerat Anand ◽

...

Keyword(s):

Clinical Trials ◽

Pharmaceutical Company ◽

Statistical Tests ◽

Research Network ◽

Cancer Clinical Trials ◽

Cancer Type ◽

New Drug ◽

Black Patients ◽

The Us ◽

Cancer Types

Abstract Background Many clinical trials supporting new drug applications underrepresent minority patients. Trials conducted by the National Cancer Institute’s National Clinical Trial’s Network (NCTN) have greater outreach to community sites, potentially allowing better representation. We compared the representation of Black patients in pharmaceutical company–sponsored cancer clinical trials with NCTN trials and with the US cancer population. Methods We established a large cohort of study publications representing the results of trials that supported new US Food and Drug Administration drug approvals from 2008 to 2018. NCTN trial data were from the SWOG Cancer Research Network. US cancer population rates were estimated using Surveillance, Epidemiology, and End Results survey data. We compared the proportion of Black patients by enrollment year for each cancer type and overall. Tests of proportions were used. All statistical tests were 2-sided. Results A total 358 trials (pharmaceutical company–sponsored trials, 85; SWOG trials, 273) comprised of 93 825 patients (pharmaceutical company–sponsored trials, 46 313; SWOG trials, 47 512) for 15 cancer types were analyzed. Overall, the proportion of Black patients was 2.9% for pharmaceutical company–sponsored trials, 9.0% for SWOG trials, and 12.1% for the US cancer population (P < .001 for each pairwise comparison). These findings were generally consistent across individual cancer types. Conclusions The poor representation of Black patients in pharmaceutical company–sponsored trials supporting new drug applications could result in the use of new drugs with little data about efficacy or side effects in this key population. Moreover, because pharmaceutical company–sponsored trials test the newest available therapies, limited access to these trials represents a disparity in access to potential breakthrough therapies.

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COVID-19: state population coverage by mask orders in the US

F1000Research ◽

10.12688/f1000research.51022.1 ◽

2021 ◽

Vol 10 ◽

pp. 120

Author(s):

Philip Jacobs ◽

Arvi Ohinmaa

Keyword(s):

Census Bureau ◽

State Governments ◽

Regional Government ◽

Population Coverage ◽

State Population ◽

News Organizations ◽

The Us ◽

Us Census ◽

Us Cities

Background: A variety of government bodies in the US - cities and tribal councils, counties, and states - have issued mask-wearing orders to prevent the spread of COVID-19. Methods: We measured the duration of these orders and the populations covered by them in each of the governed areas. We measured the in effect days from April 3, 2020 (the date of the first mask order) to November 30, 2020; the duration of the measured period amounts to 241 days. We used data generated from local and state governments, and news organizations to measure the enactment dates and the duration of the orders; and from the US Census Bureau (dated 2019) to measure municipal, county, and state populations. Results: The average coverage over all states was 57.7% of the maximum person days of coverage. States which issued statewide orders from their governors had a total of 67.1% coverage; this includes coverage from regional government orders prior to the statewide orders. States with orders only from municipal or county councils had on average 27.1% coverage. Conclusion: Overall, state governments took leadership in the implementation of mask orders.

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CLASSIFICATION OF IMMUNE SUBSETS IN SYNOVIAL FLUID OF ADVANCED OSTEOARTHRITIS PATIENTS

Journal of Musculoskeletal Research ◽

10.1142/s0218957720500177 ◽

2020 ◽

pp. 2050017

Author(s):

Molly G. Sekar ◽

Kiley A. Lawrence ◽

Matthew T. Essman ◽

Thomas Valente ◽

Katie E. Hurst ◽

...

Keyword(s):

T Cell ◽

Synovial Fluid ◽

Joint Replacement ◽

Total Joint Replacement ◽

Joint Space ◽

Facs Analysis ◽

The Us ◽

Wear And Tear

Background: Osteoarthritis (OA) is a leading cause of morbidity affecting 54 million Americans per year at an annual cost of 304 billion dollars to the US healthcare system. OA is characterized as a disease of joint wear and tear, but mounting evidence suggests a role for aberrant activation of immunity to contribute to disease progression. Methods: We hypothesized that OA patients have differential profiles of immunity between peripheral and synovial compartments as an indication that in situ immunity is affected by OA or vice versa. We used FACS analysis to phenotype T cell and myeloid populations between peripheral and synovial compartments from 16 patients undergoing total joint replacement due to advanced OA. Results: Our finding that Foxp3[Formula: see text] T regulatory (Tregs) increasingly comprise SF immunity of OA patients is novel ([Formula: see text]). Though the periphery harbored greater numbers of lymphocyte and myeloid cells compared to synovial fluid ([Formula: see text]), the synovial fluid revealed elevated percentages of myeloid (Cd11b[Formula: see text]) cells that comprised the CD45[Formula: see text] population ([Formula: see text]). Further, characterization elucidated that CD45/CD11b/CD14[Formula: see text]/CD15- cells upregulated HLADR in the affected synovial fluid ([Formula: see text]) and that these cells increase expression of CD68 ([Formula: see text]). Conclusions: Our data indicate that the affected joint space in OA patients harbors phenotypically distinct T-cell and myeloid populations compared to autologous-matched peripheral immunity. The contribution of aberrant immune populations to development and progression of OA is of interest for novel immunotherapies.

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Diversity of Tumor-Infiltrating, γδ T-Cell Abundance in Solid Cancers

Cells ◽

10.3390/cells9061537 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1537 ◽

Cited By ~ 5

Author(s):

Ghita Chabab ◽

Florence Boissière-Michot ◽

Caroline Mollevi ◽

Jeanne Ramos ◽

Evelyne Lopez-Crapez ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Γδ T Cells ◽

Tumor Infiltrating Lymphocytes ◽

Pancreatic Tumors ◽

Cell Detection ◽

Cancer Type ◽

Γδ T Cell ◽

Cancer Types ◽

T Cell Subpopulations

γδ T-cells contribute to the immune response against many tumor types through their direct cytolytic functions and their capacity to recruit and regulate the biological functions of other immune cells. As potent effectors of the anti-tumor immune response, they are considered an attractive therapeutic target for immunotherapies, but their presence and abundance in the tumor microenvironment are not routinely assessed in patients with cancer. Here, we validated an antibody for immunohistochemistry analysis that specifically detects all γδ T-cell subpopulations in healthy tissues and in the microenvironment of different cancer types. Tissue microarray analysis of breast, colon, ovarian, and pancreatic tumors showed that γδ T-cell density varies among cancer types. Moreover, the abundance of γδ tumor-infiltrating lymphocytes was variably associated with the outcome depending on the cancer type, suggesting that γδ T-cell recruitment is influenced by the context. These findings also suggest that γδ T-cell detection and analysis might represent a new and interesting diagnostic or prognostic marker.

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