New England Journal of Medicine最新文献

{"title":"Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia.","authors":"Claire Roddie, Karamjeet S Sandhu, Eleni Tholouli, Aaron C Logan, Paul Shaughnessy, Pere Barba, Armin Ghobadi, Manuel Guerreiro, Deborah Yallop, Mehrdad Abedi, Jeremy M Pantin, Jean A Yared, Amer M Beitinjaneh, Sridhar Chaganti, Katharine Hodby, Tobias Menne, Martha L Arellano, Ram Malladi, Bijal D Shah, Luke Mountjoy, Kristen M O'Dwyer, Karl S Peggs, Pierre Lao-Sirieix, Yiyun Zhang, Wolfram Brugger, Edgar Braendle, Martin Pule, Michael R Bishop, Daniel J DeAngelo, Jae H Park, Elias Jabbour","doi":"10.1056/NEJMoa2406526","DOIUrl":"10.1056/NEJMoa2406526","url":null,"abstract":"<p><strong>Background: </strong>Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence.</p><p><strong>Methods: </strong>We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease. The primary end point was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A. Secondary end points included event-free survival, overall survival, and safety.</p><p><strong>Results: </strong>Of the 153 enrolled patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. In cohort 2A (94 patients; median follow-up, 20.3 months), overall remission occurred in 77% (95% confidence interval [CI], 67 to 85), with complete remission in 55% (95% CI, 45 to 66) and complete remission with incomplete hematologic recovery in 21% (95% CI, 14 to 31). The prespecified null hypotheses of overall remission (≤40%) and complete remission (≤20%) were rejected (P<0.001). In the 127 patients who received at least one obe-cel infusion (median follow-up, 21.5 months), the median event-free survival was 11.9 months (95% CI, 8.0 to 22.1); estimated 6- and 12-month event-free survival was 65.4% and 49.5%, respectively. The median overall survival was 15.6 months (95% CI, 12.9 to not evaluable); estimated 6- and 12-month overall survival was 80.3% and 61.1%, respectively. Grade 3 or higher cytokine release syndrome developed in 2.4% of the patients, and grade 3 or higher immune effector cell-associated neurotoxicity syndrome developed in 7.1% of the patients.</p><p><strong>Conclusions: </strong>Obe-cel resulted in a high incidence of durable response among adults with relapsed or refractory B-cell ALL, with a low incidence of grade 3 or higher immune-related toxic effects. (Funded by Autolus Therapeutics; FELIX ClinicalTrials.gov number, NCT04404660.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"2219-2230"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741409","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":"Eyelid Ecchymoses and Subconjunctival Hemorrhage in Pertussis.","authors":"Leopold Simma, Maxine Gesch","doi":"10.1056/NEJMicm2409052","DOIUrl":"https://doi.org/10.1056/NEJMicm2409052","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"e59"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814863","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":"Long-Distance Spread of a Highly Drug-Resistant Epidemic Cholera Strain.","authors":"Caroline Rouard, Louis Collet, Elisabeth Njamkepo, Claire Jenkins, Rosalie Sacheli, Thierry Benoit-Cattin, Julie Figoni, François-Xavier Weill","doi":"10.1056/NEJMc2408761","DOIUrl":"https://doi.org/10.1056/NEJMc2408761","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"2271-2273"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814906","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":"Sitosterolemia with Orbital Xanthogranulomas.","authors":"Mingkun Zhan, Taosheng Huang","doi":"10.1056/NEJMicm2406958","DOIUrl":"https://doi.org/10.1056/NEJMicm2406958","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"e60"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814918","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":"Cryoglobulinemia - One Name for Two Diseases.","authors":"Paul Dalmas","doi":"10.1056/NEJMc2414268","DOIUrl":"10.1056/NEJMc2414268","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"2279-2280"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814859","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":"Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial.","authors":"Toralf Reimer, Angrit Stachs, Kristina Veselinovic, Thorsten Kühn, Jörg Heil, Silke Polata, Frederik Marmé, Thomas Müller, Guido Hildebrandt, David Krug, Beyhan Ataseven, Roland Reitsamer, Sylvia Ruth, Carsten Denkert, Inga Bekes, Dirk-Michael Zahm, Marc Thill, Michael Golatta, Johannes Holtschmidt, Michael Knauer, Valentina Nekljudova, Sibylle Loibl, Bernd Gerber","doi":"10.1056/NEJMoa2412063","DOIUrl":"https://doi.org/10.1056/NEJMoa2412063","url":null,"abstract":"<p><strong>Background: </strong>Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear.</p><p><strong>Methods: </strong>In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271.</p><p><strong>Results: </strong>A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio. The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group). The median follow-up was 73.6 months. The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin. The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%). The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy.</p><p><strong>Conclusions: </strong>In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years. (Funded by the German Cancer Aid; INSEMA ClinicalTrials.gov number, NCT02466737.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814686","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":"Drug Reaction with Eosinophilia and Systemic Symptoms.","authors":"Daniela Kroshinsky, Adela Rambi G Cardones, Kimberly G Blumenthal","doi":"10.1056/NEJMra2204547","DOIUrl":"https://doi.org/10.1056/NEJMra2204547","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"2242-2254"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814861","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":"Four Years of Screening for Prostate Cancer with PSA and MRI.","authors":"Derya Tilki, Ming-Hui Chen, Anthony V D'Amico","doi":"10.1056/NEJMc2413296","DOIUrl":"https://doi.org/10.1056/NEJMc2413296","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"2273-2274"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814902","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":"Pomalidomide in Hereditary Hemorrhagic Telangiectasia.","authors":"Atieh Modarresi, Catherine Rennie, Claire L Shovlin","doi":"10.1056/NEJMc2413110","DOIUrl":"10.1056/NEJMc2413110","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"2277-2278"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814909","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":"Bedaquiline Monotherapy for Multibacillary Leprosy.","authors":"Jaison Barreto, Patricia Sammarco Rosa, Linda Adams, Zuleima Aguilar, Nyasha Bakare, Sandra R Chaplan, Ruxandra Draghia Akli, Etienne Ernault, Sarah Kulke, Nacer Lounis, Dawn Millington, James A Palmer, Bart Remmerie, Miao Wang, Stephanie Young, Richard Truman, Paula Frassinetti Bessa Rebello","doi":"10.1056/NEJMoa2312928","DOIUrl":"10.1056/NEJMoa2312928","url":null,"abstract":"<p><strong>Background: </strong>Standard multidrug therapy for leprosy may be associated with severe side effects, which add to the stigma and discrimination that affect persons with the disease. In addition, the threat posed by drug-resistant leprosy shows the need for alternative drug combinations and shorter, safer regimens of multidrug therapy.</p><p><strong>Methods: </strong>In this open-label, proof-of-concept study conducted in Brazil, we assigned patients with previously untreated multibacillary leprosy to receive bedaquiline monotherapy for 8 weeks. After completing the 8-week course of bedaquiline, the patients started standard multidrug therapy (as defined by the World Health Organization) for leprosy and were followed for 112 weeks. The primary end point was the change from baseline in the odds of positive growth of <i>Mycobacterium leprae</i> in mouse footpads after 8 weeks of bedaquiline therapy. The secondary end point was safety. Exploratory end points included change in the clinical signs and symptoms of leprosy and in the molecular viability of <i>M. leprae</i> (measured by a quantitative reverse-transcriptase-polymerase-chain-reaction assay).</p><p><strong>Results: </strong>A total of nine patients were included in the modified intention-to-treat analysis. The odds of positive <i>M. leprae</i> growth had decreased from 100% in all the patients at baseline to no growth after 4 weeks of bedaquiline monotherapy. After 7 weeks of treatment, all the patients showed improvement in the appearance of skin lesions as compared with baseline. Seven patients had at least one adverse event (all grade 1 or 2) during treatment.</p><p><strong>Conclusions: </strong>In patients with multibacillary leprosy, bedaquiline monotherapy cleared <i>M. leprae</i> by 4 weeks of treatment and led to improvement in the appearance of skin lesions by 7 weeks. (Funded by Janssen Research and Development; ClinicalTrials.gov number, NCT03384641.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"2212-2218"},"PeriodicalIF":96.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814808","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}