JAMA Oncology最新文献

{"title":"Dasatinib and CAR T-Cell Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Nonrandomized Clinical Trial.","authors":"Mingming Zhang,Shan Fu,Jingjing Feng,Ruimin Hong,Guoqing Wei,Houli Zhao,Mengyu Zhao,Huijun Xu,Jiazhen Cui,Simao Huang,Xiaoyu Wu,Lianxuan Liu,Jie Sun,Wenjun Wu,Yuanyuan Zhu,Jingsong He,Yi Zhao,Zhen Cai,Weiyan Zheng,Xiujin Ye,Jimin Shi,Yi Luo,Dongrui Wang,Alex H Chang,Yongxian Hu,He Huang","doi":"10.1001/jamaoncol.2025.0674","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0674","url":null,"abstract":"ImportanceA combination of tyrosine kinase inhibitors and chimeric antigen receptor (CAR) T cells has made a breakthrough in refractory or relapsed Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, it remains unclear if this treatment in newly diagnosed Ph-positive ALL is associated with high rates of complete molecular remission (CMR) and leukemia-free survival.ObjectiveTo evaluate the efficacy and safety of dasatinib in combination with CAR T cells as frontline therapy in adults with newly diagnosed Ph-positive ALL.Design, Setting, and ParticipantsThis trial was conducted at a single center, the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were enrolled in this phase 2, single-arm nonrandomized clinical trial between March 5, 2021, and April 13, 2024. The data cutoff date was February 10, 2025. The data analysis was conducted on February 11, 2025. The median duration of follow-up was 23.9 (range, 7.3-47.7) months. A total of 29 adults with newly diagnosed Ph-positive ALL and adequate organ function were screened for eligibility, and 1 patient who received a diagnosis of blast-phase chronic myeloid leukemia was excluded.InterventionDasatinib was administered with a 2-week vindesine and dexamethasone regimen as induction, followed by sequential CD19 and CD22 CAR T-cell therapies and single-agent dasatinib maintenance.Main Outcomes and MeasuresThe primary end point was CMR rate after CD19 CAR T-cell therapy. CMR was defined as undetectable BCR/ABL1 transcripts as measured by quantitative reverse transcription polymerase chain reaction with a sensitivity of 10-4 in the bone marrow.ResultsTwenty-eight patients (median [range] age, 48.5 [18.0-69.0] years; 10 female individuals [36%]) were enrolled, and 1 patient withdrew after induction. The CMR rate was 25% (7 of 28) after induction and increased to 85% (23 of 27) after CD19 CAR T-cell therapy. Twenty-five patients (89.3%) received sequential CD22 CAR T-cell therapy, and the CMR rate was 76% (19 of 25). Of the 52 CAR T-cell therapies, only 21 cases of grade 1 cytokine release syndrome occurred. After a median follow-up of 23.9 (range, 7.3-47.7) months, the 2-year overall survival and leukemia-free survival were 92%.Conclusions and RelevanceThe results of this nonrandomized clinical trial suggest that the combination of dasatinib and CAR T-cell therapy showed encouraging efficacy in newly diagnosed Ph-positive ALL with acceptable toxic effects. Further studies with larger cohorts and longer follow-up durations are needed.Trial RegistrationClinicalTrials.gov Identifier: NCT04788472.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"75 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846337","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":"Overall Survival in the CAIRO5 Clinical Trial-Reply.","authors":"Marinde J G Bond,Rutger-Jan Swijnenburg,Cornelis J A Punt","doi":"10.1001/jamaoncol.2025.0610","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0610","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"9 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846334","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":"Adoption of Broad Genomic Profiling in Patients With Cancer.","authors":"Xiao Wang,John Rothen,Sida Huang,Jessica B Long,Pamela R Soulos,Sarah B Goldberg,Ronac Mamtani,Carolyn J Presley,Natalia Kunst,Shuangge Ma,Shi-Yi Wang,Cary P Gross,Michaela A Dinan","doi":"10.1001/jamaoncol.2025.0499","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0499","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"61 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846339","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":"Toward a New Paradigm in Cancer Control-Integrating Individual and Population Approaches.","authors":"William M P Klein,Alexander J Rothman","doi":"10.1001/jamaoncol.2025.0418","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0418","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846355","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":"Overall Survival in the CAIRO5 Clinical Trial.","authors":"Xiaoliang Huang,Rumao Zhong,Weizhong Tang","doi":"10.1001/jamaoncol.2025.0607","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0607","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846335","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":"Atezolizumab and Trastuzumab Plus Chemotherapy for ERBB2-Positive Locally Advanced Resectable Gastric Cancer: A Randomized Clinical Trial.","authors":"Zhi Peng,Xiaotian Zhang,Han Liang,Zhichao Zheng,Zhenning Wang,Hao Liu,Jiankun Hu,Yihong Sun,Yanqiao Zhang,Han Yan,Lin Tong,Jiahui Xu,Jiafu Ji,Lin Shen","doi":"10.1001/jamaoncol.2025.0522","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0522","url":null,"abstract":"ImportanceEffective treatment of locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer remains a challenge.ObjectiveTo compare the efficacy and safety of atezolizumab plus trastuzumab plus capecitabine and oxaliplatin chemotherapy (XELOX) vs trastuzumab plus XELOX in Chinese patients with locally advanced human epidermal growth factor receptor 2 (ERBB2; formerly HER2)-positive GC or adenocarcinoma of the GEJ.Design, Setting, and ParticipantsThis was an open-label phase 2 randomized clinical trial conducted at 8 study sites in China. Patient recruitment started on February 25, 2021, and this study is ongoing as participants are still being actively followed up. Chinese patients eligible for surgery with locally advanced ERBB2-positive GC or adenocarcinoma of the GEJ were included. Data were analyzed from March 2021 to October 2023.InterventionsEligible patients were enrolled and randomly assigned 1:1 to perioperative treatment with either atezolizumab plus trastuzumab plus XELOX (arm A) or trastuzumab plus XELOX (arm B) for 3 neoadjuvant cycles (3 weeks per cycle) and 5 adjuvant cycles.Main Outcomes and MeasuresThe primary efficacy end point was the pathological complete response (pCR) rate following completion of neoadjuvant therapy and surgery.ResultsIn total, 42 patients were screened and randomly assigned to arm A (n = 21) or arm B (n = 21). The median (range) ages were 61 (33-72) years and 65 (49-72) years in arm A and arm B, respectively, and 39 patients (93%) were male. The pCR rate was significantly higher in arm A (8 [38%]) than arm B (3 [14%]; difference, 23.8%; 90% CI, 1.3-44.7). Age younger than 65 years, male sex, and intestinal Lauren classification were significantly associated with a better pCR rate in arm A. Median event-free survival, disease-free survival, and overall survival were not reached. Based on the same way of interpretation, major pathologic response should be statistically significantly different between the 2 arms, while other outcome measures remained not significantly different. The incidence of treatment-emergent adverse events was 100% (21 of 21) and 100% (21 of 21) in arms A and B, respectively; grade 3 or higher TEAEs, 57% (12 of 21) and 67% (14 of 21), respectively; and serious TEAEs, 29% (6 of 21) and 10% (2 of 21), respectively.Conclusions and RelevanceIn this randomized clinical trial, add-on atezolizumab to trastuzumab plus XELOX therapy demonstrated promising efficacy in this patient population, and no new safety concerns were raised.Trial RegistrationClinicalTrials.gov Identifier: NCT04661150.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"88 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846347","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":"Overall Survival in the CAIRO5 Clinical Trial.","authors":"Alexej Ballhausen,Dominik Paul Modest","doi":"10.1001/jamaoncol.2025.0604","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0604","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"6 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846297","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":"Error in Key Points and Table 1.","authors":"","doi":"10.1001/jamaoncol.2025.0928","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0928","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"5 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819240","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":"Local Control and Extended Survival in Locally Advanced Hepatocellular Carcinoma.","authors":"Zhuo Song,Xuan Zheng,Weihu Wang","doi":"10.1001/jamaoncol.2025.0516","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0516","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"9 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819268","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":"Local Control and Extended Survival in Locally Advanced Hepatocellular Carcinoma-Reply.","authors":"Laura A Dawson,Kathryn A Winter,Jennifer Moughan","doi":"10.1001/jamaoncol.2025.0519","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.0519","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"14 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819267","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}