Journal of Clinical Oncology最新文献

{"title":"I Hope So Too.","authors":"Richard E Leiter","doi":"10.1200/JCO-24-02346","DOIUrl":"10.1200/JCO-24-02346","url":null,"abstract":"<p><p>Even in our most difficult moments as clinicians, we can find space to hope with our patients, if we look for it. Dr Richard Leiter tells the powerful story of caring for a young man dying of GVHD.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1516-1517"},"PeriodicalIF":42.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624847","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":"Rethinking the Path to Bladder Cancer Staging: Can Magnetic Resonance Imaging Speed Up Time to Receipt of Therapy in Patients With Muscle-Invasive Bladder Cancer?","authors":"Ashish M Kamat, Paul Frankel","doi":"10.1200/JCO-24-02482","DOIUrl":"10.1200/JCO-24-02482","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1401-1403"},"PeriodicalIF":42.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255737","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":"Olaparib as Treatment Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer: Phase III SOLO3 Study Final Overall Survival Results.","authors":"Giovanni Scambia, Ricardo Villalobos Valencia, Nicoletta Colombo, David Cibula, Charles A Leath, Mariusz Bidziński, Jae-Weon Kim, Joo Hyun Nam, Radoslaw Madry, Carlos Hernández, Paulo A R Mora, Sang Young Ryu, Mei-Lin Ah-See, Elizabeth S Lowe, Natalia Lukashchuk, Dave Carter, Richard T Penson","doi":"10.1200/JCO.24.00933","DOIUrl":"10.1200/JCO.24.00933","url":null,"abstract":"<p><p>Olaparib treatment significantly improved objective response rate (primary end point) and progression-free survival versus nonplatinum chemotherapy in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer in the open-label phase III SOLO3 trial (ClinicalTrials.gov identifier: NCT02282020). We report final overall survival (OS; prespecified secondary end point), post hoc OS analysis by number of previous chemotherapy lines, and exploratory BRCA reversion mutation analysis. Two hundred sixty-six patients were randomly assigned 2:1 to olaparib tablets (300 mg twice daily; n = 178) or physician's choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88). OS was similar with olaparib versus chemotherapy (hazard ratio [HR], 1.07 [95% CI, 0.76 to 1.49]; <i>P</i> = .71, median 34.9 and 32.9 months, respectively, full analysis set). OS with olaparib was favorable in patients with two previous chemotherapy lines (HR, 0.83 [olaparib <i>v</i> chemotherapy] [95% CI, 0.51 to 1.38]; median 37.9 <i>v</i> 28.8 months); however, a potential detrimental effect was seen in patients with at least three previous chemotherapy lines (HR, 1.33 [95% CI, 0.84 to 2.18]; median 29.9 <i>v</i> 39.4 months). BRCA reversion mutations might have contributed to this finding. No patient randomly assigned to olaparib with a BRCA reversion mutation detected at baseline (6 of 170 [3.5%]) achieved an objective tumor response.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1408-1416"},"PeriodicalIF":42.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818176","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":"Baseline Liquid Biopsy in Relation to Tissue-Based Parameters in Metastatic Colorectal Cancer: Results From the Randomized FIRE-4 (AIO-KRK-0114) Study.","authors":"Sebastian Stintzing, Susanne Klein-Scory, Ludwig Fischer von Weikersthal, Martin Fuchs, Florian Kaiser, Kathrin Heinrich, Dominik Paul Modest, Ralf-Dieter Hofheinz, Thomas Decker, Armin Gerger, Stefan Angermeier, Holger Rumpold, Andreas Dickhut, Leopold Öhler, Birgit Gruenberger, Dora Niedersuess-Beke, Matthias Sandmann, Thomas Winder, Joerg Trojan, Gerald Prager, Swantje Held, Jörg Kumbrink, Wolff Schmiegel, Alexander Baraniskin, Volker Heinemann","doi":"10.1200/JCO.24.01174","DOIUrl":"10.1200/JCO.24.01174","url":null,"abstract":"<p><strong>Purpose: </strong>The FIRE-4 study randomly assigned patients with first-line <i>RAS</i> wild-type (<i>RAS</i>wt) metastatic colorectal cancer to either flourouracil (FU), folinic acid, and irinotecan (FOLFIRI) plus cetuximab until progression or intolerable toxicity (standard arm) or to FOLFIRI plus cetuximab followed by a switch maintenance treatment using FU plus bevacizumab (experimental arm). Here, we investigate the relevance of liquid biopsy (LB) RAS and BRAF testing compared with tissue-based analyses.</p><p><strong>Patients and methods: </strong>LBs were taken at baseline and during treatment and were analyzed for <i>RAS</i> and <i>BRAF</i>^V600E mutations using the in vitro diagnostics-certified ONCOBEAM RAS procedure (Sysmex Inostics) and digital-droplet polymerase chain reaction technology.</p><p><strong>Results: </strong>Six hundred seventy-two <i>RAS</i>wt patients were randomly assigned. LBs of 540 patients were evaluable at baseline. Of those, 70 (13%) were <i>RAS</i> mutant (<i>RAS</i>mut) and 38 (7%) <i>BRAF</i>^V600E mutant. <i>RAS</i>mut patients had significantly shorter survival compared with <i>RAS</i>wt patients (progression-free survival [PFS], 9.0 months <i>v</i> 11.5 months; <i>P</i> < .001; hazard ratio [HR], 1.66; overall survival [OS], 22.1 months <i>v</i> 33.6 months; <i>P</i> < .001; HR, 1.85). <i>RAS</i>mut patients had a numerically greater benefit from early switch maintenance compared with continuation of FOLFIRI/cetuximab (PFS, 10.1 months <i>v</i> 6.4 months; HR, 0.82; OS, 24.9 months <i>v</i> 16.3 months; HR, 0.57). Patients with a <i>BRAF</i>^V600E mutation in LB showed poor outcome (PFS, 5.4 months; OS, 12.0 months). On the basis of serial LB analyses, the conversion rate from <i>RAS</i>wt to <i>RAS</i>mut at disease progression was significantly higher in the arm with continuous cetuximab administration than in the switch maintenance arm.</p><p><strong>Conclusion: </strong>LB allows the detection of <i>RAS</i> and <i>BRAF</i> mutations in patients deemed <i>RAS</i>wt on the basis of tissue analyses. These patients show outcome characteristics expected for <i>RAS</i>- and <i>BRAF</i>-mutant patients in tissue. The study thus confirms the high clinical relevance of LB performed at baseline before the start of therapy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1463-1473"},"PeriodicalIF":42.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189273","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":"Improved Survival and Prognostication in Melanoma Patients With Brain Metastases: An Update of the Melanoma Graded Prognostic Assessment.","authors":"Paul W Sperduto, Kathryn E Marqueen, Enoch Chang, Jing Li, Michael A Davies, Daniel K Ebner, William G Breen, Nayan Lamba, Helen A Shih, Donna Edwards, Michelle M Kim, Amandeep Mahal, Rifaquat Rahman, Nii Ankrah, Drexell H Boggs, Calvin Lewis, Daniel Hyer, John M Buatti, Fasila Johri, Hany Soliman, Laura Masucci, David Roberge, Sanjay Aneja, Veronica Chiang, Christina Phuong, Steve Braunstein, Salah Dajani, Sean Sachdev, Zihan Wan, Donna Niedzwiecki, Eugene Vaios, John P Kirkpatrick, Jared Pasetsky, Tony J C Wang, Tugce Kutuk, Rupesh Kotecha, Richard B Ross, Chad G Rusthoven, Toshimichi Nakano, Hussein A Tawbi, Minesh P Mehta","doi":"10.1200/JCO-24-01351","DOIUrl":"https://doi.org/10.1200/JCO-24-01351","url":null,"abstract":"<p><strong>Purpose: </strong>Survival for patients with melanoma has recently improved. The propensity of melanoma to metastasize to the brain remains a common and serious feature of this disease. The purposes of this study were to evaluate prognostic factors for patients with newly diagnosed melanoma brain metastases (MBMs) in a large cohort treated with modern multimodal therapies, compare those results with those in prior eras, and update the Melanoma Graded Prognostic Assessment (GPA).</p><p><strong>Methods: </strong>Univariable and multivariable (MVA) analyses of prognostic factors and treatments associated with survival were performed on 1,796 patients with newly diagnosed MBM treated between January 01, 2015, and December 31, 2021, using a multi-institutional retrospective database. Multiple imputation was used to address missingness of potential predictors. Significant variables in combined MVA were used to update the Melanoma GPA. Comparisons were made with legacy cohorts.</p><p><strong>Results: </strong>Median survivals for cohorts A (1985-2007, n = 481), B (2006-2015, n = 823), and C (2015-2021, n = 1,796) were 6.7, 9.8, and 16.6 months and median follow-up times were 40.1, 43.6, and 48.8 months, respectively. In combined MVA, significant prognostic factors for survival were higher Karnofsky Performance Status, fewer MBMs, absence of extracranial metastases, lower serum lactate dehydrogenase, and no immunotherapy before MBM. These factors were incorporated into the updated Melanoma GPA. The combined median and 3-year survivals for patients with GPA 0-1, 1.5-2, and 2.5-4.0 were 5.4, 13.2, and 43.2 months and 12.4%, 28.8%, and 51.6%, respectively.</p><p><strong>Conclusion: </strong>Prognostic factors have changed and survival has improved for patients with MBM but varies widely by GPA. The updated Melanoma GPA calculator (BrainMetGPA), available free online, can be used to estimate survival, individualize treatment, stratify clinical trials, guide surveillance, and augment clinical trial eligibility. Multidisciplinary treatment is essential. Trials are needed to elucidate the optimal sequencing of various therapeutic modalities.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401351"},"PeriodicalIF":42.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002638","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":"Can Improving Adjuvant Endocrine Therapy Persistence Improve Survival Outcomes for Patients With Early-Stage Breast Cancer?","authors":"Megan E Tesch, Ann H Partridge","doi":"10.1200/JCO-25-00371","DOIUrl":"https://doi.org/10.1200/JCO-25-00371","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500371"},"PeriodicalIF":42.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023490","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":"Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non-Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES/TORG1834.","authors":"Satoru Miura, Hiroshi Tanaka, Toshihiro Misumi, Hiroshige Yoshioka, Takaaki Tokito, Tatsuro Fukuhara, Yuki Sato, Yoshimasa Shiraishi, Katsuhiko Naoki, Hiroaki Akamatsu, Ou Yamaguchi, Toshihide Yokoyama, Shoichi Kuyama, Kazumi Nishino, Naoki Furuya, Takayasu Kurata, Terufumi Kato, Satoshi Ikeda, Hidehito Horinouchi, Eiki Ichihara, Masahide Mori, Yuichi Takiguchi, Kentaro Tanaka, Yasuhiro Goto, Hiroaki Okamoto","doi":"10.1200/JCO-24-02007","DOIUrl":"https://doi.org/10.1200/JCO-24-02007","url":null,"abstract":"<p><strong>Purpose: </strong>To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (<i>EGFR</i>) mutations.</p><p><strong>Methods: </strong>This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-naïve patients with nonsquamous NSCLC with uncommon <i>EGFR</i> mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary.</p><p><strong>Results: </strong>A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6 <i>v</i> 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706]; <i>P</i> = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy.</p><p><strong>Conclusion: </strong>Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon <i>EGFR</i> mutations.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402007"},"PeriodicalIF":42.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064125","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":"Development and Validation of an Artificial Intelligence Digital Pathology Biomarker to Predict Benefit of Long-Term Hormonal Therapy and Radiotherapy in Men With High-Risk Prostate Cancer Across Multiple Phase III Trials.","authors":"Andrew J Armstrong, Vinnie Y T Liu, Ramprasaath R Selvaraju, Emmalyn Chen, Jeffry P Simko, Sandy DeVries, Oliver Sartor, Howard M Sandler, Osama Mohamad, Huei-Chung Huang, Jacqueline Griffin, Rikiya Yamashita, Andre Esteva, Phuoc T Tran, Daniel E Spratt, John Hi Carson, Christopher Peters, Elizabeth Gore, Steve P Lee, Jedidiah M Monson, Mark E Augspurger, Ali El-Gayed, Joseph P Rodgers, Rana McKay, Todd Morgan, Felix Y Feng, Paul L Nguyen","doi":"10.1200/JCO.24.00365","DOIUrl":"https://doi.org/10.1200/JCO.24.00365","url":null,"abstract":"<p><strong>Purpose: </strong>Long-term androgen deprivation therapy (ADT) improves survival in men with high-risk localized prostate cancer (PCa) receiving radiotherapy (RT). Predictive biomarkers are needed to guide ADT duration.</p><p><strong>Methods: </strong>A multimodal artificial intelligence (MMAI)-derived predictive biomarker was trained for long-term (LT) versus short-term (ST) ADT using pretreatment digital prostate biopsy images and clinical data (age, prostate-specific antigen, Gleason, and T stage) from six NRG Oncology phase III randomized radiotherapy trials. The novel MMAI-derived biomarker was developed to predict the differential benefit of LT-ADT on the primary end point, distant metastasis (DM). MMAI predictive utility was validated on a seventh randomized trial, RTOG 9202 (N = 1,192), which randomly assigned men to RT + ST-ADT (4 months) versus RT + LT-ADT (28 months). Fine-Gray and cumulative incidence analyses for DM, and secondarily, death with DM, were performed. Deaths without DM were treated as competing risks.</p><p><strong>Results: </strong>In the validation cohort (median follow-up, 17.2 years), LT-ADT significantly improved DM from 26% to 17% (subdistribution hazard ratio [sHR], 0.64 [95% CI, 0.50 to 0.82], <i>P</i> < .001). A significant biomarker-treatment predictive interaction was observed (<i>P</i> = .04) for DM, whereby MMAI biomarker-positive men (n = 785, 66%) had reduced DM with LT-ADT versus ST-ADT (sHR, 0.55 [95% CI, 0.41 to 0.73], <i>P</i> < .001), whereas no treatment benefit was observed for MMAI biomarker-negative men (n = 407; sHR, 1.06 [95% CI, 0.61 to 1.84], <i>P</i> = .84). The estimated 15-year DM risk difference between RT + LT-ADT and RT + ST-ADT was 14% in MMAI biomarker-positive men and 0% in MMAI biomarker-negative men. The MMAI biomarker was also prognostic for DM, irrespective of treatment (sHR, 2.35 [95% CI, 1.72 to 3.19], <i>P</i> < .001).</p><p><strong>Conclusion: </strong>To our knowledge, the MMAI model is the first validated predictive biomarker to guide ADT duration with RT in localized/locally advanced PCa. Approximately one third of men with high-risk PCa could safely be spared the additional 24 months of ADT and the associated morbidity.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2400365"},"PeriodicalIF":42.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009396","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":"Clinical Benefit and Safety of Reduced Elective Dose in Definitive Radiotherapy for Head and Neck Squamous Cell Carcinoma: The UPGRADE-RT Multicenter Randomized Controlled Trial.","authors":"Sven van den Bosch, Patricia A H Doornaert, Frank J P Hoebers, Bas Kreike, Marije R Vergeer, Ellen M Zwijnenburg, Maurice C Cox, Gerjon Hannink, Tim Dijkema, Johannes H A M Kaanders","doi":"10.1200/JCO-24-02194","DOIUrl":"https://doi.org/10.1200/JCO-24-02194","url":null,"abstract":"<p><strong>Purpose: </strong>Definitive radiotherapy (RT) for head and neck cancer (HNC) has significant long-term toxicity with elective neck irradiation (ENI) as a major contributor. In this multicenter randomized trial, the clinical benefit and safety of definitive RT with reduced versus standard elective dose were compared.</p><p><strong>Methods: </strong>Newly diagnosed patients with cT2-4N0-2M0 HNC were accrued and treated in five Dutch centers (definitive accelerated RT, 68 Gy in 34 fractions in 5.5 weeks). Patients receiving concurrent chemotherapy were not eligible. Dose for ENI was randomly assigned (2:1; dose reduction, 43 Gy, versus control, 50 Gy). The primary outcome was normalcy of diet score at 1 year. The secondary outcome was recurrence in electively irradiated nodes at 2 years in the dose reduction group with the null hypothesis rejected if the upper-bound one-sided 95% CI exceeded 9%.</p><p><strong>Results: </strong>Between 2016 and 2022, 300 patients were randomnly assigned, of whom 295 were evaluable and included in analysis (dose reduction, 196 and control, 99). The mean normalcy of diet score at 1 year was 91.6 (95% CI, 88.5 to 94.7) in the dose reduction group and 92.6 (95% CI, 88.2 to 97.1) in the control group (mean difference, -1.1 [95% CI, -6.5 to 4.4]). The 2-year recurrence rate in electively irradiated nodes in the dose reduction group was 4.9% (upper-bound one-sided 95% CI, 7.5%). In the control group, this was 4.3% (upper bound one-sided 95% CI, 7.7%). Exploratory analyses demonstrated less acute dysphagia grade ≥3 and better xerostomia-related quality of life in the dose reduction group.</p><p><strong>Conclusion: </strong>This is the second randomized controlled trial demonstrating that reduced elective dose is safe in definitive RT for HNC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402194"},"PeriodicalIF":42.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968313","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":"Sequential Infusion of Mesenchymal Stem Cell for Graft-Versus-Host Disease Prevention in Haploidentical Hematopoietic Stem Cell Transplantation: An Open-Label, Multicenter, Randomized Controlled Clinical Trial.","authors":"Han Yao, Ruihao Huang, Haixia Fu, Ren Lin, Yanqi Zhang, Yimei Feng, Yu Wang, Ting Chen, Xiaoqi Wang, Lidan Zhu, Jia Liu, Yuqing Liu, Lu Zhao, Lu Wang, Peiyan Kong, Qin Wen, Cheng Zhang, Li Gao, Lei Gao, Qifa Liu, Xiaohui Zhang, Xiaojun Huang, Xi Zhang","doi":"10.1200/JCO-24-02119","DOIUrl":"https://doi.org/10.1200/JCO-24-02119","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this open-label, multicenter, randomized controlled trial was to determine the efficacy and safety of sequential umbilical cord-derived mesenchymal stem cell (UC-MSC) infusion for graft-versus-host disease (GVHD) prevention within 3 months of haploidentical hematopoietic stem cell transplantation (haplo-HSCT).</p><p><strong>Methods: </strong>This open-label study evaluated UC-MSC infusion (administer 1 × 10⁶/kg 4 hours before the commencement of day 0, once weekly for the first month after transplantation, once every 2 weeks for the second month, and once during the third month, totaling eight doses). The primary end point was the 2-year cumulative incidence of severe chronic GVHD (cGVHD).</p><p><strong>Results: </strong>In the primary analysis, 192 qualified participants between age 18 and 60 years with haplo-HSCT in three transplant centers in China were enrolled and randomly assigned to the MSC and control groups. In the primary analysis, the estimated 2-year cumulative incidence of severe cGVHD and all grades of cGVHD was lower in the MSC group than in the control group (<i>P</i> = .033 and <i>P</i> = .022). The cumulative incidence of grade 1 to 4, 2 to 4, and 3 to 4 acute GVHD (aGVHD) in patients in the MSC group significantly decreased (all <i>P</i> < .001). The 3-year GVHD-free and relapse-free survival (GRFS) rate in the MSC group was 62.4%, which was significantly higher than that in the control group (32.0%, hazard ratio [HR], 0.34, <i>P</i> < .001). MSC infusion did not influence the cumulative incidence of relapse (<i>P =</i> .34) and nonrelapse mortality (<i>P =</i> .45).</p><p><strong>Conclusion: </strong>Our findings suggest that sequential infusion of MSCs within 3 months after haplo-HSCT significantly reduced both the incidence and severity of cGVHD and aGVHD, manifesting as a better GRFS rate for patients.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402119"},"PeriodicalIF":42.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982021","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}