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Tumor Immunophenotypic Correlates in Patients Aged 80 Years or Older With Non-Small Cell Lung cancer and Outcomes to First-Line Pembrolizumab in PD-L1 High (≥50%) Patients

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Clinical Lung cancer 2025年第4期26卷 288-298.e8页

作者： Barrichello, Adriana P.C. Elkrief, Arielle Ricciuti, Biagio Ganta, Teja Marron, Thomas U. Wang, Xinan Lotter, William Lindsay, James Santo, Valentina Cortellini, Alessio Sharma, Bijaya Felt, Kristen Pfaff, Kathleen Lamberti, Giuseppe Pecci, Federica Federico, Alessandro Di Makarem, Maisam Gandhi, Malini M. Nguyen, Tom Haradon, Danielle Vaz, Victor R. Johnson, Bruce E. Debnath, Neha Wang, Yinghong Kuang, Andrew G. Saeed, Anwaar Radford, Maluki Lovly, Christine M. Nebhan, Caroline A. Pinato, David J. Rodig, Scott J. Schoenfeld, Adam J. Awad, Mark M. Alessi, Joao V. Naqash, Abdul Rafeh Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute Boston MA United States Thoracic Oncology Center Memorial Sloan Kettering Cancer Center New York NY United States Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY United States Department of Environmental Health Harvard T.H. Chan School of Public Health Harvard University Boston MA United States Department of Data Science Dana-Farber Cancer Institute Boston MA United States Department of Surgery and Cancer Imperial College London Faculty of Medicine Hammersmith Hospital London United Kingdom ImmunoProfile Brigham and Women's Hospital and Dana-Farber Cancer Institute Boston MA United States Center for Immuno-oncology Dana-Farber Cancer Institute Boston MA United States Department of Gastroenterology Hepatology & Nutrition University of Texas MD Anderson Cancer Center Houston TX United States Department of Internal Medicine Baylor College of Medicine Houston TX United States Division of Medical Oncology Department of Medicine Kansas University Medical Center Westwood KS United States Department of Medicine and Vanderbilt-Ingram Cancer Center Vanderbilt University Nashville TN United States Department of Pathology Brigham and Women's Hospital Boston MA United States Medical Oncology/TSET Phase 1 Program Stephenson Cancer Center University of Oklahoma Oklahoma City OK United States

Background: Non-small cell lung cancer (NSCLC) patients aged ≥80 years [y] are underrepresented in clinical trials. We evaluated whether age correlates with a distinct immunophenotype or impacts outcomes to first-line pembrolizumab in patients with advanced NSCLC, PD-L1 Tumor Proportion Score (TPS) of ≥50%, and aged ≥80y. Methods: Three NSCLC cohorts were retrospectively analyzed to assess the impact of age (<80y versus ≥80y) on pembrolizumab efficacy and the tumor microenvironment (TME). Cohort A encompassed patients receiving first-line pembrolizumab for advanced NSCLC with PD-L1 ≥50%. Cohort B comprised patients with tumor profiling using multiplexed immunofluorescence (ImmunoPROFILE). Cohort C included The cancer Genome Atlas (TCGA) and Stand Up to cancer (SU2C) databases for gene expression analysis. Results: In Cohort A (N = 669), patients ≥80y (N = 111) showed no significant differences in objective response rate or median progression-free survival compared to younger patients (N = 558), but had shorter median overall survival and were less likely to receive second-line therapy after progression on pembrolizumab. In Cohort B (N = 567), tumors from patients ≥80y (N = 45) exhibited higher intratumoral FOXP3+ T cells and closer vicinity of PD-1+ immune cells to tumor cells compared to <80y (N = 522). Cohort C revealed a distinct immunophenotype in samples from patients ≥ 80y, with elevated specific immune cell subsets and up-regulated immune checkpoint proteins. Conclusion: Patients ≥80y with PD-L1-high NSCLC displayed a distinct immunophenotype in the TME but achieved similar ORR and mPFS with first-line pembrolizumab compared to younger patients. OS was shorter in older patients, who were less likely to receive second-line therapy. © 2025 Elsevier Inc.

关键词： Immune cells Immunotherapy Older adults Thoracic tumors Tumor microenvironment

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Precision Rehabilitation for Patients Post-Stroke based on Electronic Health Records and Machine Learning

arXiv

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arXiv 2024年

作者： Gao, Fengyi Zhang, Xingyu Sivarajkumar, Sonish Denny, Parker E. Aldhahwani, Bayan M. Visweswaran, Shyam Shi, Ryan Hogan, William Bove, Allyn Wang, Yanshan Department of Health Information Management University of Pittsburgh PittsburghPA United States Department of Communication Science and Disorders University of Pittsburgh PittsburghPA United States Intelligent Systems Program School of Computing and Information University of Pittsburgh PittsburghPA United States Department of Physical Therapy University of Pittsburgh PittsburghPA United States Department of Medical Rehabilitation Sciences Umm Al-Qura University Makkah Saudi Arabia Department of Biomedical Informatics University of Pittsburgh PittsburghPA United States Department of Computer Science University of Pittsburgh Medical Center PittsburghPA United States Data Science Institute Medical College of Wisconsin MilwaukeeWI United States Hillman Cancer Center University of Pittsburgh Medical Center PittsburghPA United States

Objective In this study, we utilized statistical analysis and machine learning methods to examine whether rehabilitation exercises can improve patients post-stroke functional abilities, as well as forecast the improvement in functional abilities. Our dataset is patients’ rehabilitation exercises and demographic information recorded in the unstructured electronic health records (EHRs) data and free-text rehabilitation procedure notes. Through this study, our ultimate goal is to pinpoint the specific rehabilitation exercises that can effectively aid post-stroke patients in improving their functional outcomes in basic mobility (BM) and applied cognitive (AC) domains. data sources We collected data for 265 stroke patients from the University of Pittsburgh Medical Center, accessed through the Rehabilitation datamart With Informatics iNfrastructure for Research (ReDWINE). Methods We employed a pre-existing natural language processing (NLP) algorithm to extract data on rehabilitation exercises and developed a rule-based NLP algorithm to extract Activity Measure for Post-Acute Care (AM-PAC) scores, covering basic mobility (BM) and applied cognitive (AC) domains, from procedure notes. AM-PAC scores were collected at the initial rehabilitation visit and followed up at one and two months—key recovery periods. Changes in AM-PAC scores were classified based on the minimal clinically important difference (MCID), and significance was assessed using Friedman and Wilcoxon tests. To identify impactful exercises, we used Chi-square tests, Fisher's exact tests, and logistic regression for odds ratios. Additionally, we developed five machine learning models—logistic regression (LR), Adaboost (ADB), support vector machine (SVM), gradient boosting (GB), and random forest (RF)—to predict outcomes in functional ability. Results Statistical analyses revealed significant associations between functional improvements and specific exercises. In the AC domain, the BALANCE exercise showed substant

关键词： Statistical tests

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Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS)

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Nature Communications 2025年第1期16卷 1-13页

作者： Barroso-Sousa, Romualdo Zanudo, Jorge Gomez Tejeda Li, Tianyu Reddy, Sangeetha M. Emens, Leisha A. Kuntz, Thomas M. Silva, Carolina Alves Costa AlDubayan, Saud H. Chu, Hoyin Overmoyer, Beth Lange, Paulina DiLullo, Molly K. Montesion, Meagan Kasparian, Julie Hughes, Melissa E. Attaya, Victoria Basta, Ameer Lin, Nancy U. Tayob, Nabihah Jeselsohn, Rinath Mittendorf, Elizabeth A. Tolaney, Sara M. Hospital Brasília Rede Américas Brasilia Brazil Medical Oncology Dana-Farber Cancer Institute Boston MA United States Breast Oncology Program Dana-Farber Brigham Cancer Center Boston MA United States Harvard Medical School Boston MA United States Data Science Dana-Farber Cancer Institute Boston MA United States University of Texas Southwestern Medical Center Dallas TX United States University of Pittsburgh Medical Center Pittsburgh PA United States Department of Biostatistics Harvard T. H. Chan School of Public Health Boston MA United States Gustave Roussy Cancer Campus (GRCC) Clinicobiome Cedex Villejuif France Foundation Medicine Inc. Boston MA United States Division of Breast Surgery Department of Surgery Brigham and Women’s Hospital Boston MA United States

In the phase II NIMBUS trial, patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) and high tumor mutational burden (TMB ≥ 9 mut/Mb) received nivolumab (3 mg/kg biweekly) and low-dose ipilimumab (1 mg/kg every 6 weeks) for 2 years or until progression. The primary endpoint was objective response rate (ORR) per RECIST 1.1 criteria. Among 30 patients enrolled, the median TMB was 10.9 mut/Mb (range: 9–110) and the confirmed objective response rate was 20%. Secondary endpoints included progression-free survival, overall survival, clinical benefit rate, and safety and tolerability, including immune-related adverse events (irAEs). A prespecified correlative outcome was to evaluate the ORR in patients with a TMB ≥ 14 mut/Mb. Patients with TMB ≥ 14 mut/Mb (n = 6) experienced higher response rates (60% vs 12%;p = 0.041) and showed a trend towards improved progression-free survival and overall survival compared to patients with TMB < 14 mut/Mb. Exploratory genomic analyses suggested that ESR1 and PTEN mutations may be associated with poor response, while clinical benefit was associated with a decrease or no change in tumor fraction by serial circulating tumor DNA during treatment. Stool microbiome analysis revealed that baseline blood TMB, PD-L1 positivity, and immune-related diarrhea are associated with distinct taxonomic profiles. In summary, some patients with hypermutated HER2-negative MBC experience extended clinical benefit with a dual immunotherapy regimen;a higher TMB, and additional genomic and microbiome biomarkers may optimize patient selection for therapy with nivolumab plus low-dose ipilimumab. (Funded by Bristol Myers Squibb;*** identifier, NCT03789110). © The Author(s) 2025.

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Projected Time for the Elimination of Cervical cancer Under Various Intervention Scenarios: Age-Period-Cohort Macrosimulation Study

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JMIR Public Health and Surveillance 2024年 10卷 e46360页

作者： Chen, Yi-Chu Chen, Yun-Yuan Su, Shih-Yung Jhuang, Jing-Rong Chiang, Chun-Ju Yang, Ya-Wen Lin, Li-Ju Wu, Chao-Chun Lee, Wen-Chung Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei Taiwan Head Office Taiwan Blood Services Foundation Taipei Taiwan Master Program in Statistics National Taiwan University Taipei Taiwan Institute of Statistical Science Academia Sinica Taipei Taiwan Taiwan Cancer Registry Taipei city Taiwan Health Promotion Administration Ministry of Health and Welfare Taipei Taiwan Institute of Health Data Analytics College of Public Health National Taiwan University Taipei Taiwan

BACKGROUND: The World Health Organization aims for the global elimination of cervical cancer, necessitating modeling studies to forecast long-term outcomes. OBJECTIVE: This paper introduces a macrosimulation framework using age-period-cohort modeling and population attributable fractions to predict the timeline for eliminating cervical cancer in Taiwan. METHODS: data for cervical cancer cases from 1997 to 2016 were obtained from the Taiwan cancer Registry. Future incidence rates under the current approach and various intervention strategies, such as scaled-up screening (cytology based or human papillomavirus [HPV] based) and HPV vaccination, were projected. RESULTS: Our projections indicate that Taiwan could eliminate cervical cancer by 2050 with either 70% compliance in cytology-based or HPV-based screening or 90% HPV vaccination coverage. The years projected for elimination are 2047 and 2035 for cytology-based and HPV-based screening, respectively;2050 for vaccination alone;and 2038 and 2033 for combined screening and vaccination approaches. CONCLUSIONS: The age-period-cohort macrosimulation framework offers a valuable policy analysis tool for cervical cancer control. Our findings can inform strategies in other high-incidence countries, serving as a benchmark for global efforts to eliminate the disease. ©Yi-Chu Chen, Yun-Yuan Chen, Shih-Yung Su, Jing-Rong Jhuang, Chun-Ju Chiang, Ya-Wen Yang, Li-Ju Lin, Chao-Chun Wu, Wen-Chung Lee. Originally published in JMIR Public Health and Surveillance (https://***), 18.04.2024.

关键词： Age-period-cohort model cancer screening Cervical cancer Cervical screening HPV Human papillomavirus Intervention Macrosimulation Population attributable fraction Public health intervention Women

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Managing the transition in cervical screening methods for Taiwan: Policy recommendations and perspectives

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Journal of the Formosan Medical Association 2023年第11期122卷 1213-1218页

作者： Chen, Chien-Chin Lai, Chyong-Huey Chang, Chih-Long Cheng, Wen-Fang Pwu, Raoh-Fang Tsai, Jane Wang, Peng-Hui Whang-Peng, Jacqueline Lai, Gi-Ming Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi 600 Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan 717 Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 402 Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan Department of Obstetrics and Gynecology Chang Gung Memorial Hospital Linkou Branch Taoyuan 333 Taiwan Chang Gung University Taoyuan 333 Taiwan Department of Medicine MacKay Medical College New Taipei City 252 Taiwan Department of Obstetrics and Gynecology MacKay Memorial Hospital Taipei 104 Taiwan Department of Obstetrics and Gynecology College of Medicine National Taiwan University Taipei 100 Taiwan School of Health Care Administration Taipei Medical University Taipei 110 Taiwan Data Science Center Fu Jen Catholic University New Taipei City 242 Taiwan Formosa Cancer Foundation Taipei 105 Taiwan Department of Obstetrics and Gynecology Taipei Veterans General Hospital Taipei 112 Taiwan National Yang Ming Chiao Tung University Taipei 112 Taiwan

Since government-provided annual cervical cytology testing for all Taiwanese women aged 30 years or older became available in 1995, both cervical cancer incidence and death have decreased significantly. However, with the 2018 introduction of the national immunization program for human papillomavirus (HPV) vaccination in all schoolgirls aged 13–15 years old, the positive predictive value of cytology testing is expected to decrease with rising vaccination rates, and therefore a transition to more sensitive HPV-based testing may be needed. This position paper, derived from discussions by a panel of experts in cervical cancer screening, provides short-, medium-, and long-term policy recommendations to manage the transition between cervical screening methods for Taiwan. The recommendations include concrete suggestions regarding testing procedures, standards, accreditation, monitoring, promotion, and implementation. It is hoped that comprehensive preparation and management of this transition will enable Taiwan to repeat the previous successes of the cervical cytology testing program. © 2023 Formosan Medical Association

关键词： Cervical cancer Cervical cytology HPV-based testing Human papillomavirus Pap smear

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Expression of HLA-B35 Is Associated with an Increased Risk of CMV Viremia and Clinically Significant CMV Infection in Patients Receiving Ptcy-Based Hematopoietic Cell Transplantation

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Transplantation and Cellular Therapy 2025年第2期31卷 S519-S519页

作者： Little, Jessica S., MD Hebert, Kyle, MS Neuberg, Donna, ScD Nikiforow, Sarah, MD, PhD Gooptu, Mahasweta, MD Shapiro, Roman M., MD Koreth, John, MBBS, DPhil Antin, Joseph H., MD Cutler, Corey S., MD MPH Soiffer, Robert J., MD Ritz, Jerome, MD Romee, Rizwan, MD Ho, Dr. Vincent T., MD Issa, Nicolas, M.D. Baden, Lindsey, MD Dulery, Remy, MD, PhD Prockop, Susan E., MD Division of Stem Cell Transplantation and Cellular Therapy Dana-Farber Cancer Institute and Harvard Medical School Boston MA Division of Infectious Diseases Brigham and Women's Hospital Boston MA Department of Data Science Dana-Farber Cancer Institute Boston MA Department of Data Science Dana Farber Cancer Institute Boston MA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA Department of Medical Oncology Dana-Farber Cancer Institute and Harvard Medical School Boston MA Dana-Farber Cancer Institute Boston MA Division of Stem Cell Transplant and Cellular Therapy Dana-Farber Cancer Institute and Harvard Medical School Boston MA Hematopoietic Stem Cell Transplant Program Dana Farber Cancer Institute Boston Children's Hospital and Harvard Medical School Boston MA

IntroductionHematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis carries a higher risk of cytomegalovirus (CMV) infections despite letermovir prophylaxis. T cell immune responses are crucial for controlling viral infections like CMV, but PTCy may reduce TCR repertoire diversity. A prior study (Hasan A, et al. Blood Adv 2022) showed impaired CMV control by CMVpp65 CTLs restricted by HLA-B35 alleles. We hypothesized that HLA-B35 expression could be a risk factor for CMV infections post-PTCy-based HCT with in-vivo T cell depletion. MethodsIn this single-center retrospective study, we included consecutive adults at risk for CMV reactivation (recipient and/or donor seropositive) undergoing HCT with PTCy from February 2015 to February 2022. CMV viremia and clinically significant CMV infection (CS-CMVi; CMV viremia/disease requiring CMV therapy) were assessed. Letermovir prophylaxis through D100 was used for CMV-seropositive recipients after 2017. Fine-Gray sub-distribution hazards models identified risk factors for CS-CMVi and CMV viremia, with disease relapse, repeat HCT, or death as competing risks. Cytokine release syndrome (CRS), neutrophil recovery, and acute/chronic GVHD were included as time-varying covariates. The Dana-Farber Harvard cancer Center (DF/HCC) Institutional Review Board approved the study. ResultsOf 211 patients included, 59% were male, with a median age of 60 years (19.4 – 78.3). Acute myeloid leukemia (39%) and myelodysplastic syndrome/myeloproliferative neoplasms (29%) were the most common diseases. Donor were haploidentical (55%), HLA-mismatched unrelated (26%), and HLA-matched unrelated (19%). The majority of recipients were CMV seropositive (78%) and 60% received letermovir prophylaxis. HLA-B35 was carried by 18% patients. Transplant-related complications included CRS (47%), acute GVHD (42%), and chronic GVHD (27%). The one-year cumulative incidence of CS-CMVi was 29.9%

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Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial

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The Lancet Oncology 2025年第5期26卷 559-570页

作者： Lou, Emil Choudhry, Modassir S Starr, Timothy K Folsom, Timothy D Bell, Jason Rathmann, Blaine DeFeo, Anthony P Kim, Jihyun Slipek, Nicholas Jin, Zhaohui Sumstad, Darin Klebanoff, Christopher A Ladner, Katherine Sarkari, Akshat McIvor, R Scott Murray, Thomas A Miller, Jeffrey S Rao, Madhuri Jensen, Eric Ankeny, Jacob Khalifa, Mahmoud A Chauhan, Anil Spilseth, Benjamin Dixit, Ajay Provenzano, Paolo P Pan, Wenjing Weber, Daniel Byrne-Steele, Miranda Henley, Tom McKenna, David H Johnson, Matthew J Webber, Beau R Moriarity, Branden S Department of Medicine Division of Hematology Oncology and Transplantation University of Minnesota Minneapolis MN United States Department of Obstetrics Gynecology and Women's Health University of Minnesota Minneapolis MN United States Department of Pediatrics University of Minnesota Minneapolis MN United States Masonic Cancer Center University of Minnesota Minneapolis MN United States Center for Genome Engineering University of Minnesota Minneapolis MN United States Department of Genetics Cell Biology and Development University of Minnesota Minneapolis MN United States Department of Biomedical Engineering University of Minnesota Minneapolis MN United States Center for Multiparametric Imaging of Tumor Immune Microenvironments University of Minnesota Minneapolis MN United States Stem Cell Institute University of Minnesota Minneapolis MN United States Intima Bioscience New York NY United States Deparment of Medical Oncology Mayo Clinic Rochester MN United States Cell Therapy Clinical Laboratory University of Minnesota Medical School Minneapolis MN United States Division of Biostatistics and Health Data Science University of Minnesota Medical School Minneapolis MN United States Department of Surgery University of Minnesota Medical School Minneapolis MN United States Department of Laboratory Medicine and Pathology University of Minnesota Medical School Minneapolis MN United States Department of Radiology University of Minnesota Medical School Minneapolis MN United States Department of Medicine Human Oncology and Pathogenesis Program and Parker Institute for Cancer Immunotherapy Memorial Sloan Kettering Cancer Center New York NY United States Department of Radiology University of Kansas Medical Center Kansas City KS United States Division of Gastroenterology Hepatology and Nutrition Cincinnati Children's Hospital Medical Center Cincinnati OH United States iRepertoire Huntsville AL United States

Background: Over the past decade, immunotherapeutic strategies—mainly targeting the PD-1–PD-L1 immune checkpoint axis—have altered cancer treatment for many solid tumours, but few patients with gastrointestinal forms of cancer have benefited to date. There remains an urgent need to extend immunotherapy efficacy to more patients while addressing resistance to current immune checkpoint inhibitors. The aim of this study was to determine the safety and anti-tumour activity of knockout of CISH, which encodes cytokine-inducible SH2-containing protein, a novel intracellular immune checkpoint target and a founding member of the SOCS family of E3-ligases, using tumour infiltrating lymphocyte (TILs) genetically edited with CRISPR-Cas9 in patients with metastatic gastrointestinal epithelial cancers. Methods: For this first-in-human, single-centre, phase 1 trial, patients aged 18–70 years with a diagnosis of metastatic gastrointestinal epithelial cancer with progressive disease following at least one first line standard therapy, measurable disease with at least one lesion identified as resectable for TIL generation and at least one other lesion meeting RECIST criteria as measurable to serve as an indicator of disease response, and an ECOG performance status of 0 or 1 were screened and enrolled if meeting these and all other eligibility criteria. TILs procured from tumour biopsies were expanded on the basis of neoantigen reactivity, subjected to CRISPR-Cas9-mediated CISH knockout, and infused intravenously into 12 patients after non-myeloablative lymphocyte depleting chemotherapy (cyclophosphamide 60 mg/kg per dose on study days –6 and –5, and fludarabine 25 mg/m² per dose on days –7 to –3) followed by high-dose IL-2 (aldesleukin;720 000 IU/kg per dose). The primary endpoint was safety of administration of neoantigen-reactive TILs with knockout of the CISH gene, and a key secondary endpoint was anti-tumour activity measured as objective radiographic response and progr

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Correction to: Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy (Nature Biotechnology, (2025), 10.1038/s41587-024-02535-2)

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Nature Biotechnology 2025年

作者： Zhang, Feifei Chow, Ryan D. He, Emily Dong, Chuanpeng Xin, Shan Mirza, Daniyal Feng, Yanzhi Tian, Xiaolong Verma, Nipun Majety, Medha Zhang, Yueqi Wang, Guangchuan Chen, Sidi Department of Genetics Yale University School of Medicine New HavenCT United States System Biology Institute Yale University West HavenCT United States Center for Cancer Systems Biology Yale University West HavenCT United States M.D.–Ph.D. Program Yale University West HavenCT United States Molecular Cell Biology Genetics and Development Program Yale University New HavenCT United States Yale College New HavenCT United States Immunobiology Program Yale University New HavenCT United States Department of Therapeutic Radiology Yale University School of Medicine New HavenCT United States Department of Neurosurgery Yale University School of Medicine New HavenCT United States Yale Comprehensive Cancer Center Yale University School of Medicine New HavenCT United States Yale Stem Cell Center Yale University School of Medicine New HavenCT United States Yale Center for Biomedical Data Science Yale University School of Medicine New HavenCT United States Key Laboratory of Multi-Cell Systems Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Shanghai China

Correction to: Nature Biotechnologyhttps://***/10.1038/s41587-024-02535-2, published online 16 January 2025. In the version of the article initially published, Sidi Chen was incorrectly associated with a present address. This has now been corrected in the HTML and PDF versions of the article. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.

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Outcomes of Patients with Hematologic Malignancies and COVID-19 Infection: A Report from the ASH Research Collaborative data Hub

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BLOOD 2020年 136卷 7-8页

作者： Wood, William A. Neuberg, Donna S. Thompson, John Colton Tallman, Martin S. Sekeres, Mikkael A. Sehn, Laurie H. Anderson, Kenneth Goldberg, Aaron D. Pennell, Nathan A. Niemeyer, Charlotte M. Tucker, Emily Hewitt, Kathleen Plovnick, Robert M. Hicks, Lisa K. Division of Hematology Department of Medicine University of North Carolina Chapel Hill NC Department of Data Science Dana-Farber Cancer Institute Boston MA ASH Research Collaborative Washington DC Memorial Sloan-Kettering Cancer Center New York NY Leukemia Program Department of Hematology and Medical Oncology Cleveland Clinic Taussig Cancer Institute Cleveland OH British Columbia Cancer Agency Vancouver Canada Jerome Lipper Multiple Myeloma Center LeBow Institute for Myeloma Therapeutics Dana-Farber Cancer Institute Harvard Medical School Boston MA Department of Medicine Leukemia Service Memorial Sloan-Kettering Cancer Center New York NY Lung Program Medical Oncology Cleveland Clinic Taussig Cancer Institute Cleveland OH University Children's Hospital Freiburg Germany ASH Research Collaborative Washington DC DC American Society of Hematology Washington DC DC Division of Hematology/Oncology St. Michael's Hospital Toronto Canada

Introduction: The coronavirus disease 2019 (COVID-19) is an illness resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019. Many patients with blood cancer have underlying immune dysfunction, and many are treated with chemotherapies and immunotherapies that are themselves profoundly immunosuppressive. Additionally, patients with blood cancer are often older, may have comorbid illness including hypertension and diabetes, and may be especially susceptible to complications of COVID-19 include hypercoagulability and thrombosis. For patients with hematologic malignancies, overall risk of morbidity and mortality from COVID-19 infection, and how this risk varies as a function of age, disease status, type of malignancy, and cancer therapy, has not yet been well defined. Methods: The ASH Research Collaborative COVID-19 Registry for Hematology was developed to study features and outcomes of COVID-19 infection in patients with underlying blood disorders, such as hematologic malignancies. The Registry opened for data collection on April 1, 2020. The Registry is a global effort and is housed on a secure data platform hosted by Prometheus Research, an IQVIA company. The Registry collects data from patients of all ages with a current or history of hematological disease, and either a laboratory-confirmed or presumptive diagnosis of SARS-CoV-2 infection. data are made available and regularly updated on the ASH Research Collaborative website to guide the provider and patient communities. data presented here are limited to malignant hematologic diseases only. Contributors are individual providers or designees submitting data on behalf of providers. Results: At the time of this analysis, data from 250 patients with blood cancers from 74 sites around the world had been entered into the Registry. The most commonly represented malignancies were acute leukemia (33%), non-Hodgkin lymphoma (27%), and myeloma or amyloidosis (16%). Patients presen

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Phase I Study of Ixazomib with Conventional Chemotherapy in the Treatment of Acute Myeloid Leukemia in Older Adults

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BLOOD 2020年 136卷 7-8页

作者： Amrein, Philip C. Attar, Eyal C. Fell, Geoffrey Blonquist, Traci M. Brunner, Andrew M. Hobbs, Gabriela S. Hock, Hanno R. McAfee, Steven L. Narayan, Rupa Moran, Jenna A. Bergeron, Meghan Foster, Julia E. Bertoli, Christina McGregor, Kristin Macrae, Molly Burke, Meghan Behnan, Tanya T. Som, Tina T. Ramos, Aura Y. Vartanian, Megan K. Story, Jennifer Lombardi Neuberg, Donna S. Fathi, Amir T. Leukemia Center/MGH Cancer Center Massachusetts General Hospital Belmont MA Agios Boston MA Data Science Dana-Farber Cancer Institute Boston MA Center for Leukemia Massachusetts General Hospital Boston MA Leukemia Center Massachusetts General Hospital Boston MA Leukemia Center Massachusetts General Hospital / Harvard Medical School Boston MA Massachusetts General Hospital Blood and Marrow Transplant Program Boston MA Leukemia Center Massachusetts General Hospital Center for Leukemia Cambridge MA

Introduction: Outcomes for acute myeloid leukemia (AML) among older patients has remained largely unchanged for decades. Long-term survival for patients aged >60 years is poor (median survival 10.5 months). Targeting the proteasome in AML is attractive, since leukemia stem cells have demonstrated sensitivity to proteasome inhibition in preclinical models, perhaps through down regulation of nuclear NF-KB (Guzman, Blood 2001). AML cell lines are susceptible to synergistic cytotoxicity when bortezomib, a proteasome inhibitor, is combined with daunorubicin and cytarabine. We have shown that adding bortezomib to standard treatment in AML results in a high remission rate, although grade 2 sensory neurotoxicity was noted in approximately 12% of treated patients. A newer generation proteasome inhibitor, ixazomib, is less frequently associated with neurotoxicity, and, therefore, was selected for combination with conventional chemotherapy in this phase I trial. The primary objective of this study was to determine the maximum tolerated dose (MTD) of ixazomib in combination with conventional induction and consolidation chemotherapy for AML. Herein are the initial results of this trial. Methods: Adults >60 years of age with newly diagnosed AML were screened for eligibility. Patients with secondary AML were eligible, including those with prior hypomethylating agent therapy for myelodysplastic syndromes (MDS). We excluded those with promyelocytic leukemia. There were 2 phases in this study. In the first phase (A), the induction treatment consisted of the following: cytarabine 100 mg/m2/day by continuous IV infusion, Days 1-7; daunorubicin 60 mg/m2/day IV, Days 1, 2, 3, and ixazomib was provided orally at the cohort dose, Days 2, 5, 9, and 12. Consolidaton or transplant was at the discretion of the treating physician in phase A. In the second phase (B), induction was the same as that with the determined MTD of ixazomib. All patients were to be treated with the following consolidati

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