New England Journal of Medicine最新文献

{"title":"CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in <i>TP53</i>.","authors":"Karlo Perica, Nayan Jain, Michael Scordo, Ruchi Patel, Ozgur Can Eren, Utsav Patel, Gunes Gundem, Dylan Domenico, Sneha Mitra, Nicholas D Socci, John K Everett, Aoife M Roche, Angelina Petrichenko, Gunjan L Shah, Maria E Arcila, Laetitia Borsu, Jae H Park, Steven M Horwitz, Sergio A Giralt, Ahmet Dogan, Christina Leslie, Elli Papaemmanuil, Frederic D Bushman, Saad Z Usmani, Michel Sadelain, Sham Mailankody","doi":"10.1056/NEJMoa2411507","DOIUrl":"10.1056/NEJMoa2411507","url":null,"abstract":"<p><p>Malignant T-cell transformation after chimeric antigen receptor (CAR) T-cell therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. Here we report a case of a T-cell lymphoma harboring a lentiviral integration in a known tumor suppressor, <i>TP53</i>, which developed in a patient with multiple myeloma after B-cell maturation antigen (BCMA) CAR T-cell therapy.</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"577-583"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Plaques en Prairie Fauchée</i> Tongue Lesions in Secondary Syphilis.","authors":"Jonathan P Angel","doi":"10.1056/NEJMicm2411077","DOIUrl":"https://doi.org/10.1056/NEJMicm2411077","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"e18"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Zenocutuzumab in <i>NRG1</i> Fusion-Positive Cancer.","authors":"Alison M Schram, Koichi Goto, Dong-Wan Kim, Teresa Macarulla, Antoine Hollebecque, Eileen M O'Reilly, Sai-Hong Ignatius Ou, Jordi Rodon, Sun Young Rha, Kazumi Nishino, Michaël Duruisseaux, Joon Oh Park, Cindy Neuzillet, Stephen V Liu, Benjamin A Weinberg, James M Cleary, Emiliano Calvo, Kumiko Umemoto, Misako Nagasaka, Christoph Springfeld, Tanios Bekaii-Saab, Grainne M O'Kane, Frans Opdam, Kim A Reiss, Andrew K Joe, Ernesto Wasserman, Viktoriya Stalbovskaya, Jim Ford, Shola Adeyemi, Lokesh Jain, Shekeab Jauhari, Alexander Drilon","doi":"10.1056/NEJMoa2405008","DOIUrl":"https://doi.org/10.1056/NEJMoa2405008","url":null,"abstract":"<p><strong>Background: </strong>Neuregulin 1 (<i>NRG1</i>) fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways. The efficacy and safety of zenocutuzumab, a bispecific antibody against HER2 and HER3, in patients with <i>NRG1</i> fusion-positive solid tumors are unclear.</p><p><strong>Methods: </strong>In this registrational, phase 2 clinical study, we assigned patients with advanced <i>NRG1</i> fusion-positive cancer involving any tumor type to receive zenocutuzumab at a dose of 750 mg intravenously every 2 weeks. The primary end point was overall response (complete or partial response) according to investigator assessment. Secondary end points included duration of response, progression-free survival, and safety.</p><p><strong>Results: </strong>A total of 204 patients with 12 tumor types were enrolled and treated. Among 158 patients who had measurable disease and were enrolled at least 24 weeks before the data-cutoff date, a response occurred in 30% (95% confidence interval [CI], 23 to 37). The median duration of response was 11.1 months (95% CI, 7.4 to 12.9); 19% of responses were ongoing at the data-cutoff date. Responses were observed in multiple tumor types - including in 27 of 93 patients (29%; 95% CI, 20 to 39) with non-small-cell lung cancer (NSCLC) and 15 of 36 patients (42%; 95% CI, 25 to 59) with pancreatic cancer - and across multiple <i>NRG1</i> fusion partners. The median progression-free survival was 6.8 months (95% CI, 5.5 to 9.1). Adverse events were primarily grade 1 or 2. The most common adverse events that were considered by the investigator to be related to zenocutuzumab were diarrhea (in 18% of the patients), fatigue (in 12%), and nausea (in 11%). Infusion-related reactions (composite term) were observed in 14% of the patients. One patient discontinued zenocutuzumab owing to a treatment-related adverse event.</p><p><strong>Conclusions: </strong>Zenocutuzumab showed efficacy in patients with advanced <i>NRG1</i> fusion-positive cancer, notably NSCLC and pancreatic cancer, with mainly low-grade adverse events. (Funded by Merus; eNRGy ClinicalTrials.gov number, NCT02912949.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"566-576"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Durvalumab in Bladder Cancer.","authors":"Shunsuke Koga, Lin Mei","doi":"10.1056/NEJMc2415733","DOIUrl":"https://doi.org/10.1056/NEJMc2415733","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"618-619"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lead Poisoning.","authors":"Marcela Tamayo-Ortiz, Maria Jose Talayero, Paulina Farías","doi":"10.1056/NEJMc2415108","DOIUrl":"https://doi.org/10.1056/NEJMc2415108","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"623-624"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterine Fibroids. Reply.","authors":"Elizabeth A Stewart, Shannon K Laughlin-Tommaso","doi":"10.1056/NEJMc2415479","DOIUrl":"https://doi.org/10.1056/NEJMc2415479","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"622"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Durvalumab in Bladder Cancer. Reply.","authors":"Thomas Powles, Matthew D Galsky, Michiel S van der Heijden","doi":"10.1056/NEJMc2415733","DOIUrl":"https://doi.org/10.1056/NEJMc2415733","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"619"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lead Poisoning.","authors":"Kelly Johnson-Arbor","doi":"10.1056/NEJMc2415108","DOIUrl":"https://doi.org/10.1056/NEJMc2415108","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"623"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lead Poisoning.","authors":"Pien Rawee, Michele F Eisenga","doi":"10.1056/NEJMc2415108","DOIUrl":"https://doi.org/10.1056/NEJMc2415108","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"623"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lead Poisoning. Reply.","authors":"Bruce Lanphear, Ana Navas-Acien, David C Bellinger","doi":"10.1056/NEJMc2415108","DOIUrl":"https://doi.org/10.1056/NEJMc2415108","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 6","pages":"624"},"PeriodicalIF":96.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}