المؤلفون: Patel, Sandip, Alonso-Gordoa, Teresa, Banerjee, Susana, Wang, Ding, Naidoo, Jarushka, Standifer, Nathan, Palmer, Doug, Cheng, Lin-Yang, Kourtesis, Panagiotis, Ascierto, Maria, Das, Mayukh, Diamond, Jennifer, Hellmann, Matthew, Carneiro, Benedito

المصدر: Journal for ImmunoTherapy of Cancer. 12(2)

مصطلحات موضوعية: Adaptive Immunity, Immunity, Innate, Natural Killer T-Cells, Programmed Cell Death 1 Receptor, Tumor Microenvironment, Female, Humans, Adolescent, Adult, Carcinoma, Non-Small-Cell Lung, Ligands, Lung Neoplasms, Tumor Microenvironment, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized

الوصف: BACKGROUND: The combination of monalizumab (anti-NKG2A/CD94) and durvalumab (anti-programmed death ligand-1) may promote antitumor immunity by targeting innate and adaptive immunity. This phase 1/2 study of monalizumab and durvalumab evaluated safety, antitumor activity, and pharmacodynamics in patients with advanced solid tumors. MAIN BODY: Immunotherapy-naïve patients aged ≥18 years with advanced disease, Eastern Cooperative Oncology Group performance status of 0-1, and 1-3 prior lines of systemic therapy in the recurrent/metastatic setting were enrolled. In part 1 (dose escalation), patients received durvalumab 1500 mg every 4 weeks (Q4W) with increasing doses of monalizumab Q2W/Q4W (n=15). Dose expansion in part 1 included patients with cervical cancer (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W) or metastatic microsatellite stable (MSS)-colorectal cancer (CRC) (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q4W). In part 2 (dose expansion), patients with MSS-CRC (n=40), non-small cell lung cancer (NSCLC; n=20), MSS-endometrial cancer (n=40), or ovarian cancer (n=40) received durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W. The primary endpoint was safety. Secondary endpoints included antitumor activity per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Exploratory analyses included assessment of T-cell and natural killer (NK) cell activation and proliferation in peripheral blood and the tumor microenvironment (TME). The study enrolled 185 patients (part 1, 45; part 2, 140). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. In part 2, the most common treatment-related adverse events were fatigue (12.1%), asthenia (9.3%), diarrhea (9.3%), pruritus (7.9%), and pyrexia (7.1%). In the expansion cohorts, response rates were 0% (cervical), 7.7% (MSS-CRC), 10% (NSCLC), 5.4% (ovarian), and 0% (MSS-endometrial). Sustained NK cell activation, CD8+ T-cell proliferation, increased serum levels of CXCL10 (C-X-C motif chemokine ligand 10) and CXCL11, and increased tumor infiltration of CD8+ and granzyme B+ cells were observed. CONCLUSIONS: Although efficacy was modest, monalizumab plus durvalumab was well tolerated and encouraging immune activation was observed in the peripheral blood and TME. TRIAL REGISTRATION NUMBER: NCT02671435.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2888m63bTest

المؤلفون: Burnette, Hannah, Pabani, Aliyah, von Itzstein, Mitchell S, Switzer, Benjamin, Fan, Run, Ye, Fei, Puzanov, Igor, Naidoo, Jarushka, Ascierto, Paolo A, Gerber, David E, Ernstoff, Marc S, Johnson, Douglas B

المساهمون: Susan and Luke Simons Directorship for Melanoma, Division of Cancer Prevention, National Cancer Institute, Van Stephenson Melanoma Fund, James C. Bradford Melanoma Fund

المصدر: Journal for ImmunoTherapy of Cancer ; volume 12, issue 5, page e008599 ; ISSN 2051-1426

الوصف: Background Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed. Their utility to answer questions surrounding immune-related adverse events (irAEs), common and potentially dangerous toxicities from cancer immunotherapy, are not well defined. Methods We developed 50 distinct questions with answers in available guidelines surrounding 10 irAE categories and queried two AI chatbots (ChatGPT and Bard), along with an additional 20 patient-specific scenarios. Experts in irAE management scored answers for accuracy and completion using a Likert scale ranging from 1 (least accurate/complete) to 4 (most accurate/complete). Answers across categories and across engines were compared. Results Overall, both engines scored highly for accuracy (mean scores for ChatGPT and Bard were 3.87 vs 3.5, p<0.01) and completeness (3.83 vs 3.46, p<0.01). Scores of 1–2 (completely or mostly inaccurate or incomplete) were particularly rare for ChatGPT (6/800 answer-ratings, 0.75%). Of the 50 questions, all eight physician raters gave ChatGPT a rating of 4 (fully accurate or complete) for 22 questions (for accuracy) and 16 questions (for completeness). In the 20 patient scenarios, the average accuracy score was 3.725 (median 4) and the average completeness was 3.61 (median 4). Conclusions AI chatbots provided largely accurate and complete information regarding irAEs, and wildly inaccurate information (“hallucinations”) was uncommon. However, until accuracy and completeness increases further, appropriate guidelines remain the gold standard to follow

الإتاحة: https://doi.org/10.1136/jitc-2023-008599Test

المؤلفون: Daetwyler, Eveline, Wallrabenstein, Till, König, David, Cappelli, Laura C., Naidoo, Jarushka, Zippelius, Alfred, Läubli, Heinz

المصدر: Journal for ImmunoTherapy of Cancer. - 12, 1 (2024) , e007409, ISSN: 2051-1426

الوصف: Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient’s immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, ...

وصف الملف: pdf

العلاقة: https://freidok.uni-freiburg.de/data/243584Test

الإتاحة: https://doi.org/10.1136/jitc-2023-007409Test
https://freidok.uni-freiburg.de/data/243584Test
https://nbn-resolving.org/urn:nbn:de:bsz:25-freidok-2435841Test
https://freidok.uni-freiburg.de/dnb/download/243584Test

المؤلفون: Chen, Steven T, Semenov, Yevgeniy R, Alloo, Allireza, Bach, Daniel Q, Betof Warner, Allison, Bougrine, Amina, Burton, Leeann, Cappelli, Laura C, Castells, Mariana, Cohen, Justine, Dewan, Anna K, Fadden, Riley, Guggina, Lauren, Hegde, Aparna, Huang, Victor, Johnson, Douglas B, Kaffenberger, Benjamin, Kroshinsky, Daniela, Kwatra, Shawn, Kwong, Bernice, Lacouture, Mario E, Larocca, Cecilia, Leventhal, Jonathan, Markova, Alina, McDunn, Jon, Mooradian, Meghan J, Naidoo, Jarushka, Choi, Jennifer, Nambudiri, Vinod, Nelson, Caroline A, Patel, Anisha B, Pimkina, Julia, Rine, Johnathan, Rubin, Krista M, Sauder, Maxwell, Shaigany, Sheila, Shariff, Afreen, Sullivan, Ryan J, Zubiri, Leyre, Reynolds, Kerry L, LeBoeuf, Nicole R

المصدر: Journal for ImmunoTherapy of Cancer ; volume 12, issue 4, page e007675 ; ISSN 2051-1426

الوصف: With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence of immune-related adverse events (irAEs) is on the rise. Dermatologic immune-related adverse events (D-irAEs) are the most common and earliest to manifest, often with important downstream consequences for the patient. Current guidelines lack clarity in terms of diagnostic criteria for D-irAEs. The goal of this project is to better define D-irAE for the purposes of identification, diagnosis, and future study of this important group of diseases. The objectives of this project were to develop consensus guidance for an approach to D-irAEs including disease definitions and severity grading. Knowing that consensus among oncologists, dermatologists, and irAE subspecialists would be critical for usability, we formed a Dermatologic irAE Disease Definition Panel. The panel was composed of 34 experts, including oncologists, dermatologists, a rheumatologist, and an allergist/immunologist from 22 institutions across the USA and internationally. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two virtual meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness, and accuracy on 9-point scales in electronic surveys and provided free text comments. A working group aggregated survey responses and incorporated them into revised definitions. Consensus was based on numeric ratings using the RAND/UCLA Appropriateness Method with prespecified definitions. Following revisions based on panelist feedback, all items received consensus in the second round of ratings. Consensus definitions were achieved for 10 core D-irAE diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover’s, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, and ICI-erosive mucocutaneous. A standard evaluation for D-irAE was also found to reach consensus, with disease-specific exceptions detailed ...

الإتاحة: https://doi.org/10.1136/jitc-2023-007675Test

المؤلفون: Keogh, Rachel J., Barr, Martin P., Keogh, Anna, McMahon, David, O’Brien, Cathal, Finn, Stephen P., Naidoo, Jarushka

المصدر: JTO Clinical and Research Reports ; volume 5, issue 2, page 100627 ; ISSN 2666-3643

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Oncology

الإتاحة: https://doi.org/10.1016/j.jtocrr.2023.100627Test
https://api.elsevier.com/content/article/PII:S2666364323001704?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666364323001704?httpAccept=text/plainTest

المؤلفون: Vansteenkiste, Johan F., Naidoo, Jarushka, Faivre-Finn, Corinne, Özgüroğlu, Mustafa, Villegas, Augusto, Daniel, Davey, Murakami, Shuji, Hui, Rina, Lee, Ki Hyeong, Cho, Byoung Chul, Kubota, Kaoru, Broadhurst, Helen, Wadsworth, Catherine, Newton, Michael, Thiyagarajah, Piruntha, Antonia, Scott J.

المساهمون: NIHR Maudsley Biomedical Research Centre, AstraZeneca

المصدر: JTO Clinical and Research Reports ; volume 5, issue 3, page 100638 ; ISSN 2666-3643

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Oncology

الإتاحة: https://doi.org/10.1016/j.jtocrr.2024.100638Test
https://api.elsevier.com/content/article/PII:S2666364324000080?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666364324000080?httpAccept=text/plainTest

المؤلفون: O’Leary, Caroline L., Pierce, Nicole, Patel, Sandip P., Naidoo, Jarushka

المساهمون: RCSI University of Medicine and Health Sciences

المصدر: Journal of Thoracic Oncology ; volume 19, issue 3, page 395-408 ; ISSN 1556-0864

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Oncology

الإتاحة: https://doi.org/10.1016/j.jtho.2023.11.018Test
https://api.elsevier.com/content/article/PII:S1556086423023742?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1556086423023742?httpAccept=text/plainTest

المؤلفون: Naidoo, Jarushka, Reinmuth, Niels, Puzanov, Igor, Bar, Jair, Kamer, Iris, Koch, Ina, Moskovitz, Mor, Levy-Barda, Adva, Agbarya, Abed, Zer, Alona, Abu-Amna, Mahmoud, Farrugia, David, Lotem, Michal, Price, Gillian, Harkovsky, Tatiana, Hassani, Adam, Katzenelson, Rivka, Chatterjee, Anirban, Yelin, Ben, Sela, Itamar, Dicker, Adam, Elon, Yehonatan, Harel, Michal, Leibowitz, Raya

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2023-sitc2023.1229Test

المؤلفون: Kao, Chester J, Charmsaz, Soren, Brancati, Madalena, Alden, Stephanie L, Li, Howard L, Balaji, Aanika, Munjal, Kabeer, Tsai, Hua-Ling, Danilova, Ludmila, Hernandez, Alexei, Gross, Nicole, Coyne, Erin M, Shin, Sarah M, Durham, Jennifer, Christmas, Brian, Thoburn, Christopher, Konig, Maximilian F, Lipson, Evan J, Naidoo, Jarushka, Cappelli, Laura, Ged, Yasser, Barretti, Marina, Brahmer, Julie, Hoffman-Censits, Jean, Seiwert, Tanguy Y, Garonce-Hediger, Rachel, Bansal, Sanjay, Tang, Laura, Jaffee, Elizabeth M, Scott Chandler, G, Mohindra, Rajat, Ho, Won Jin, Yarchoan, Mark

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2023-sitc2023.1245Test

المؤلفون: Zhang, Jun, Arrieta, Oscar, Naidoo, Jarushka

المصدر: Frontiers Research Topics ; ISSN 1664-8714 ; ISBN 9782832535424

الإتاحة: https://doi.org/10.3389/978-2-8325-3548-6Test