Komal L Jhaveri, Patrick Neven, Monica Lis Casalnuovo, Sung-Bae Kim, Eriko Tokunaga, Philippe Aftimos, Cristina Saura, Joyce O'Shaughnessy, Nadia Harbeck, Lisa A Carey, Giuseppe Curigliano, Antonio Llombart-Cussac, Elgene Lim, María de la Luz García Tinoco, Joohyuk Sohn, André Mattar, Qingyuan Zhang, Chiun-Sheng Huang, Chih-Chiang Hung, Jorge Luis Martinez Rodriguez, Manuel Ruíz Borrego, Rikiya Nakamura, Kamnesh R Pradhan, Christoph Cramer von Laue, Emily Barrett, Shanshan Cao, Xuejing Aimee Wang, Lillian M Smyth, François-Clément Bidard
{"title":"Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.","authors":"Komal L Jhaveri, Patrick Neven, Monica Lis Casalnuovo, Sung-Bae Kim, Eriko Tokunaga, Philippe Aftimos, Cristina Saura, Joyce O'Shaughnessy, Nadia Harbeck, Lisa A Carey, Giuseppe Curigliano, Antonio Llombart-Cussac, Elgene Lim, María de la Luz García Tinoco, Joohyuk Sohn, André Mattar, Qingyuan Zhang, Chiun-Sheng Huang, Chih-Chiang Hung, Jorge Luis Martinez Rodriguez, Manuel Ruíz Borrego, Rikiya Nakamura, Kamnesh R Pradhan, Christoph Cramer von Laue, Emily Barrett, Shanshan Cao, Xuejing Aimee Wang, Lillian M Smyth, François-Clément Bidard","doi":"10.1056/NEJMoa2410858","DOIUrl":"https://doi.org/10.1056/NEJMoa2410858","url":null,"abstract":"<p><strong>Background: </strong>Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα (<i>ESR1</i>).</p><p><strong>Methods: </strong>In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib. Primary end points were investigator-assessed progression-free survival with imlunestrant as compared with standard therapy among patients with <i>ESR1</i> mutations and among all patients and with imlunestrant-abemaciclib as compared with imlunestrant among all patients who had undergone randomization concurrently.</p><p><strong>Results: </strong>Overall, 874 patients underwent randomization, with 331 assigned to imlunestrant, 330 to standard therapy, and 213 to imlunestrant-abemaciclib. Among 256 patients with <i>ESR1</i> mutations, the median progression-free survival was 5.5 months with imlunestrant and 3.8 months with standard therapy. The estimated restricted mean survival time at 19.4 months was 7.9 months (95% confidence interval [CI], 6.8 to 9.1) with imlunestrant and 5.4 months (95% CI, 4.6 to 6.2) with standard therapy (difference, 2.6 months; 95% CI, 1.2 to 3.9; P<0.001). In the overall population, the median progression-free survival was 5.6 months with imlunestrant and 5.5 months with standard therapy (hazard ratio for progression or death, 0.87; 95% CI, 0.72 to 1.04; P = 0.12). Among 426 patients in the comparison of imlunestrant-abemaciclib with imlunestrant, the median progression-free survival was 9.4 months and 5.5 months, respectively (hazard ratio, 0.57; 95% CI, 0.44 to 0.73; P<0.001). The incidence of grade 3 or higher adverse events was 17.1% with imlunestrant, 20.7% with standard therapy, and 48.6% with imlunestrant-abemaciclib.</p><p><strong>Conclusions: </strong>Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with <i>ESR1</i> mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of <i>ESR1</i>-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807739","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":"Could Lentivirus Overcome the AAV Gene-Therapy Challenges in Hemophilia A?","authors":"Johnny Mahlangu","doi":"10.1056/NEJMe2414214","DOIUrl":"https://doi.org/10.1056/NEJMe2414214","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803541","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}
Shane W English, Anthony Delaney, Dean A Fergusson, Michaël Chassé, Alexis F Turgeon, François Lauzier, Angie Tuttle, Ofer Sadan, Donald E Griesdale, Gary Redekop, Martin Chapman, Mathew Hannouche, Andreas Kramer, Ian Seppelt, Andrew Udy, Demetrios J Kutsogiannis, Ryan Zarychanski, Frédérick D'Aragon, J Gordon Boyd, Gavin Salt, Judith Bellapart, Gordon Wood, Luis Cava, Gwynedd Pickett, Lauren Koffman, Irene Watpool, Frances Bass, Naomi Hammond, Tim Ramsay, Ranjeeta Mallick, Damon C Scales, Christopher R Andersen, Emily Fitzgerald, Phil Talbot, Dar Dowlatshahi, John Sinclair, Jason Acker, Shawn C Marshall, Lauralyn McIntyre
{"title":"Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage.","authors":"Shane W English, Anthony Delaney, Dean A Fergusson, Michaël Chassé, Alexis F Turgeon, François Lauzier, Angie Tuttle, Ofer Sadan, Donald E Griesdale, Gary Redekop, Martin Chapman, Mathew Hannouche, Andreas Kramer, Ian Seppelt, Andrew Udy, Demetrios J Kutsogiannis, Ryan Zarychanski, Frédérick D'Aragon, J Gordon Boyd, Gavin Salt, Judith Bellapart, Gordon Wood, Luis Cava, Gwynedd Pickett, Lauren Koffman, Irene Watpool, Frances Bass, Naomi Hammond, Tim Ramsay, Ranjeeta Mallick, Damon C Scales, Christopher R Andersen, Emily Fitzgerald, Phil Talbot, Dar Dowlatshahi, John Sinclair, Jason Acker, Shawn C Marshall, Lauralyn McIntyre","doi":"10.1056/NEJMoa2410962","DOIUrl":"https://doi.org/10.1056/NEJMoa2410962","url":null,"abstract":"<p><strong>Background: </strong>The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear.</p><p><strong>Methods: </strong>We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (optional transfusion at a hemoglobin level of ≤8 g per deciliter). The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 12 months. Secondary outcomes included 12-month functional independence as assessed with the Functional Independence Measure (FIM; scores range from 18 to 126) and quality of life as assessed with the EuroQol five-dimension, five-level (EQ-5D-5L) utility index (scores range from -0.1 to 0.95) and a visual analogue scale (VAS; scores range from 0 to 100); on each assessment, higher scores indicate better health status or quality of life.</p><p><strong>Results: </strong>A total of 742 patients underwent randomization at 23 centers. The analysis of the primary outcome at 12 months included 725 patients (97.7%). An unfavorable neurologic outcome occurred in 122 of 364 patients (33.5%) in the liberal-strategy group and in 136 of 361 patients (37.7%) in the restrictive-strategy group (risk ratio, 0.88; 95% confidence interval [CI], 0.72 to 1.09; P = 0.22). The mean (±SD) FIM score was 82.8±54.6 in the liberal-strategy group and 79.8±54.5 in the restrictive-strategy group (mean difference, 3.01; 95% CI, -5.49 to 11.51). The mean EQ-5D-5L utility index score was 0.5±0.4 in both groups (mean difference, 0.02; 95% CI, -0.04 to 0.09). The mean VAS score was 52.1±37.5 in the liberal-strategy group and 50±37.1 in the restrictive-strategy group (mean difference, 2.08; 95% CI, -3.76 to 7.93). The incidence of adverse events was similar in the two groups.</p><p><strong>Conclusions: </strong>In patients with aneurysmal subarachnoid hemorrhage and anemia, a liberal transfusion strategy did not result in a lower risk of an unfavorable neurologic outcome at 12 months than a restrictive strategy. (Funded by the Canadian Institutes of Health Research and others; SAHARA ClinicalTrials.gov number, NCT03309579.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803544","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}
Winnie Byanyima, Linda-Gail Bekker, Matthew M Kavanagh
{"title":"Long-Acting HIV Medicines and the Pandemic Inequality Cycle - Rethinking Access.","authors":"Winnie Byanyima, Linda-Gail Bekker, Matthew M Kavanagh","doi":"10.1056/NEJMms2412286","DOIUrl":"https://doi.org/10.1056/NEJMms2412286","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803546","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}
Meletios A Dimopoulos, Peter M Voorhees, Fredrik Schjesvold, Yael C Cohen, Vania Hungria, Irwindeep Sandhu, Jindriska Lindsay, Ross I Baker, Kenshi Suzuki, Hiroshi Kosugi, Mark-David Levin, Meral Beksac, Keith Stockerl-Goldstein, Albert Oriol, Gabor Mikala, Gonzalo Garate, Koen Theunissen, Ivan Spicka, Anne K Mylin, Sara Bringhen, Katarina Uttervall, Bartosz Pula, Eva Medvedova, Andrew J Cowan, Philippe Moreau, Maria-Victoria Mateos, Hartmut Goldschmidt, Tahamtan Ahmadi, Linlin Sha, Annelore Cortoos, Eva G Katz, Els Rousseau, Liang Li, Robyn M Dennis, Robin Carson, S Vincent Rajkumar
{"title":"Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma.","authors":"Meletios A Dimopoulos, Peter M Voorhees, Fredrik Schjesvold, Yael C Cohen, Vania Hungria, Irwindeep Sandhu, Jindriska Lindsay, Ross I Baker, Kenshi Suzuki, Hiroshi Kosugi, Mark-David Levin, Meral Beksac, Keith Stockerl-Goldstein, Albert Oriol, Gabor Mikala, Gonzalo Garate, Koen Theunissen, Ivan Spicka, Anne K Mylin, Sara Bringhen, Katarina Uttervall, Bartosz Pula, Eva Medvedova, Andrew J Cowan, Philippe Moreau, Maria-Victoria Mateos, Hartmut Goldschmidt, Tahamtan Ahmadi, Linlin Sha, Annelore Cortoos, Eva G Katz, Els Rousseau, Liang Li, Robyn M Dennis, Robin Carson, S Vincent Rajkumar","doi":"10.1056/NEJMoa2409029","DOIUrl":"https://doi.org/10.1056/NEJMoa2409029","url":null,"abstract":"<p><strong>Background: </strong>Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved.</p><p><strong>Methods: </strong>In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria.</p><p><strong>Results: </strong>Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified.</p><p><strong>Conclusions: </strong>Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803542","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}
Alok Srivastava, Aby Abraham, Fouzia Aboobacker, Gurbind Singh, Tulasi Geevar, Uday Kulkarni, Sushil Selvarajan, Anu Korula, Rutvi Gautam Dave, Mohana Shankar, Abraham S Singh, Anbu Jeba, Navien Kumaar, Christopher Benjamin, Kavitha M Lakshmi, Vivi Miriam Srivastava, Ramachandran V Shaji, Sukesh C Nair, Harrison C Brown, Gabriela Denning, Pete Lollar, Christopher B Doering, Trent Spencer
{"title":"Lentiviral Gene Therapy with CD34+ Hematopoietic Cells for Hemophilia A.","authors":"Alok Srivastava, Aby Abraham, Fouzia Aboobacker, Gurbind Singh, Tulasi Geevar, Uday Kulkarni, Sushil Selvarajan, Anu Korula, Rutvi Gautam Dave, Mohana Shankar, Abraham S Singh, Anbu Jeba, Navien Kumaar, Christopher Benjamin, Kavitha M Lakshmi, Vivi Miriam Srivastava, Ramachandran V Shaji, Sukesh C Nair, Harrison C Brown, Gabriela Denning, Pete Lollar, Christopher B Doering, Trent Spencer","doi":"10.1056/NEJMoa2410597","DOIUrl":"https://doi.org/10.1056/NEJMoa2410597","url":null,"abstract":"<p><strong>Background: </strong>Severe hemophilia A is managed with factor VIII replacement or hemostatic products that stop or prevent bleeding. Data on gene therapy with hematopoietic stem-cell (HSC)-based expression of factor VIII for the treatment of severe hemophilia A are lacking.</p><p><strong>Methods: </strong>We conducted a single-center study involving five participants 22 to 41 years of age with severe hemophilia A without factor VIII inhibitors. Autologous HSCs were transduced with CD68-LV-ET3 - a lentiviral vector including a new <i>F8</i> transgene (<i>ET3</i>) with a myeloid-directed CD68 promoter - either without transduction enhancer (group 1) or with transduction enhancer (group 2). Transduced HSCs were transplanted into recipients after myeloablative conditioning. The treatment was assessed for safety (engraftment and regimen-related toxic effects) and efficacy (factor VIII activity and annualized bleeding rate).</p><p><strong>Results: </strong>Participants received CD68-ET3-LV-transduced autologous CD34+ HSCs at doses of 5.0×10<sup>6</sup> to 6.1×10<sup>6</sup> per kilogram of body weight. The vector copy numbers in the final drug product were 1.0 and 0.6 copies per cell for the two participants in group 1 and 1.5, 0.6, and 2.2 copies per cell for the three participants in group 2. The duration of severe neutropenia was 7 to 11 days and of severe thrombocytopenia was 1 to 7 days. The median factor VIII activity level, measured with the use of a one-stage assay, after day 28 until the last follow-up visit was 5.2 IU per deciliter (range, 3.0 to 8.7) and 1.7 IU per deciliter (range, 1.0 to 4.0) with a peripheral-blood vector copy number of 0.2 and 0.1 copies per cell, respectively, in the two group 1 participants, and 37.1 IU per deciliter (range, 18.3 to 73.6), 19.3 IU per deciliter (range, 6.6 to 34.5), and 39.9 IU per deciliter (range, 20.6 to 55.1) with a peripheral-blood vector copy number of 4.4, 3.2, and 4.8 copies per cell, respectively, in the three group 2 participants. The annualized bleeding rate was zero for all five participants over a cumulative follow-up of 81 months (median follow-up, 14 months; range, 9 to 27).</p><p><strong>Conclusions: </strong>Gene therapy for hemophilia A with the use of lentiviral vector-transduced autologous HSCs resulted in stable factor VIII expression, with factor VIII activity correlating to vector copy number in the peripheral blood. (Funded by the Ministry of Science and Technology, Government of India, and others; ClinicalTrials.gov number, NCT05265767; Clinical Trials Registry-India number, CTRI/2022/03/041304.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803543","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}
Sumit Gupta, Rachel E Rau, John A Kairalla, Karen R Rabin, Cindy Wang, Anne L Angiolillo, Sarah Alexander, Andrew J Carroll, Susan Conway, Lia Gore, Ilan Kirsch, Holly R Kubaney, Amanda M Li, Jennifer L McNeer, Olga Militano, Tamara P Miller, Yvonne Moyer, Maureen M O'Brien, Maki Okada, Shalini C Reshmi, Mary Shago, Elizabeth Wagner, Naomi Winick, Brent L Wood, Tara Haworth-Wright, Faraz Zaman, Gerhard Zugmaier, Sue Zupanec, Meenakshi Devidas, Stephen P Hunger, David T Teachey, Elizabeth A Raetz, Mignon L Loh
{"title":"Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.","authors":"Sumit Gupta, Rachel E Rau, John A Kairalla, Karen R Rabin, Cindy Wang, Anne L Angiolillo, Sarah Alexander, Andrew J Carroll, Susan Conway, Lia Gore, Ilan Kirsch, Holly R Kubaney, Amanda M Li, Jennifer L McNeer, Olga Militano, Tamara P Miller, Yvonne Moyer, Maureen M O'Brien, Maki Okada, Shalini C Reshmi, Mary Shago, Elizabeth Wagner, Naomi Winick, Brent L Wood, Tara Haworth-Wright, Faraz Zaman, Gerhard Zugmaier, Sue Zupanec, Meenakshi Devidas, Stephen P Hunger, David T Teachey, Elizabeth A Raetz, Mignon L Loh","doi":"10.1056/NEJMoa2411680","DOIUrl":"https://doi.org/10.1056/NEJMoa2411680","url":null,"abstract":"<p><strong>Background: </strong>B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.</p><p><strong>Methods: </strong>We conducted a phase 3 trial involving children with newly diagnosed standard-risk B-cell ALL who had an average or high risk of relapse. Patients were randomly assigned to receive chemotherapy alone or chemotherapy plus two nonsequential 28-day cycles of blinatumomab. The primary end point was disease-free survival.</p><p><strong>Results: </strong>The data and safety monitoring committee reviewed the results from the first interim efficacy analysis, which included 1440 patients who had undergone randomization (722 to chemotherapy alone and 718 to blinatumomab and chemotherapy) and recommended early termination of randomization. At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9±2.1% with chemotherapy alone (difference in restricted mean survival time, 72 days; 95% confidence interval, 36 to 108; P<0.001 by stratified log-rank test). The estimated 3-year disease-free survival among patients with an average relapse risk was 97.5±1.3% with blinatumomab and chemotherapy and 90.2±2.3% with chemotherapy alone; among those with a high relapse risk, the corresponding values were 94.1±2.5% and 84.8±3.8%. Cytokine release syndrome, seizures, and sepsis of grade 3 or higher were rare during blinatumomab cycles, but the overall incidence of nonfatal sepsis and catheter-related infections was significantly higher among patients with an average relapse risk who had been assigned to receive blinatumomab and chemotherapy than among those assigned to receive chemotherapy alone.</p><p><strong>Conclusions: </strong>Adding blinatumomab to combination chemotherapy in patients with newly diagnosed childhood standard-risk B-cell ALL of average or high risk of relapse significantly improved disease-free survival. (Funded by the National Institutes of Health and others; AALL1731 ClinicalTrials.gov number, NCT03914625.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803540","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":"Handcuffs and Unexpected Deaths - \"I Can't Breathe\" as a Medical Emergency.","authors":"Matt Bivens, Eric Jaeger, Victor Weedn","doi":"10.1056/NEJMp2407162","DOIUrl":"https://doi.org/10.1056/NEJMp2407162","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774766","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":"Mycosis Fungoides of the Palms and Soles.","authors":"Chen Li, Wen-Hui Wang","doi":"10.1056/NEJMicm2401673","DOIUrl":"https://doi.org/10.1056/NEJMicm2401673","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774776","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":"The Care That Saved Me.","authors":"Sarah McCarthy","doi":"10.1056/NEJMp2407628","DOIUrl":"https://doi.org/10.1056/NEJMp2407628","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774781","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}