Edward Abadir , Rebecca Wayte , Wenlong Li , Sachin Gupta , Shihong Yang , Elizabeth Reaiche , Katrina Debosz , Emily Anderson , James Favaloro , Esther Aklilu , Christina Brown , Christian Bryant , Scott Dunkley , Derek McCulloch , Stephen Larsen , John E.J. Rasko , Vinay Vanguru , P. Joy Ho
{"title":"大B细胞淋巴瘤患者在两次或两次以上治疗后,输注后CAR - T扩增减少与生存率低相关。","authors":"Edward Abadir , Rebecca Wayte , Wenlong Li , Sachin Gupta , Shihong Yang , Elizabeth Reaiche , Katrina Debosz , Emily Anderson , James Favaloro , Esther Aklilu , Christina Brown , Christian Bryant , Scott Dunkley , Derek McCulloch , Stephen Larsen , John E.J. Rasko , Vinay Vanguru , P. Joy Ho","doi":"10.1016/j.jtct.2025.01.001","DOIUrl":null,"url":null,"abstract":"<div><div>CD19-directed chimeric antigen receptor T cell (CAR-T) therapy is now standard of care for relapsed/refractory large B cell non-Hodgkin lymphoma. Despite good overall response rates, many patients still experience disease progression and therefore it is important to predict those at risk of relapse following CAR-T therapy. We performed a prospective study using a flow cytometry assay at a single treatment center to assess early CAR T cell expansion in vivo 6 to 9 days after CAR T cell infusion. Early CAR T cell expansion was used in conjunction with additional clinical risk factors to identify those at greater risk of relapse or treatment failure. Forty-four patients treated with commercial CD19-directed CAR-T therapy were included in the study, with a median follow-up of 306 days. CAR T cell expansion of >30 cells/μL was associated with a lower risk of disease progression or death (hazard ratio, 0.34; <em>P</em> = .048), but did not correlate with the risk of death alone. Patients who had poor early CAR T cell expansion (<30 cells/μL) in addition to high lactate dehydrogenase (LDH) had significantly lower median progression-free survival and overall survival. High LDH level alone was not a statistically significant risk factor for death or disease progression, and thus the interaction between CAR T cell expansion and this clinical risk factor may be important in predicting response. The mean CAR T cell count was higher in patients with grade 2 to 4 cytokine release syndrome (CRS) compared to those with grade 0 to 1 CRS (54.9 cells/μL versus 25.5 cells/μL; <em>P</em> = .01). The methodology of this assay is easily reproducible outside of a clinical trial, allowing for real-life implementation in clinical settings. This study suggests that early assessment of CAR T cell expansion can assist in identifying patients with poor overall survival who may benefit from early intervention or more intensive monitoring.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 159-165"},"PeriodicalIF":3.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Reduced Chimeric Antigen Receptor T Cell Expansion Postinfusion Is Associated with Poor Survival in Patients with Large B Cell Lymphoma after Two or More Therapies\",\"authors\":\"Edward Abadir , Rebecca Wayte , Wenlong Li , Sachin Gupta , Shihong Yang , Elizabeth Reaiche , Katrina Debosz , Emily Anderson , James Favaloro , Esther Aklilu , Christina Brown , Christian Bryant , Scott Dunkley , Derek McCulloch , Stephen Larsen , John E.J. Rasko , Vinay Vanguru , P. Joy Ho\",\"doi\":\"10.1016/j.jtct.2025.01.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>CD19-directed chimeric antigen receptor T cell (CAR-T) therapy is now standard of care for relapsed/refractory large B cell non-Hodgkin lymphoma. Despite good overall response rates, many patients still experience disease progression and therefore it is important to predict those at risk of relapse following CAR-T therapy. We performed a prospective study using a flow cytometry assay at a single treatment center to assess early CAR T cell expansion in vivo 6 to 9 days after CAR T cell infusion. Early CAR T cell expansion was used in conjunction with additional clinical risk factors to identify those at greater risk of relapse or treatment failure. Forty-four patients treated with commercial CD19-directed CAR-T therapy were included in the study, with a median follow-up of 306 days. CAR T cell expansion of >30 cells/μL was associated with a lower risk of disease progression or death (hazard ratio, 0.34; <em>P</em> = .048), but did not correlate with the risk of death alone. Patients who had poor early CAR T cell expansion (<30 cells/μL) in addition to high lactate dehydrogenase (LDH) had significantly lower median progression-free survival and overall survival. High LDH level alone was not a statistically significant risk factor for death or disease progression, and thus the interaction between CAR T cell expansion and this clinical risk factor may be important in predicting response. The mean CAR T cell count was higher in patients with grade 2 to 4 cytokine release syndrome (CRS) compared to those with grade 0 to 1 CRS (54.9 cells/μL versus 25.5 cells/μL; <em>P</em> = .01). The methodology of this assay is easily reproducible outside of a clinical trial, allowing for real-life implementation in clinical settings. This study suggests that early assessment of CAR T cell expansion can assist in identifying patients with poor overall survival who may benefit from early intervention or more intensive monitoring.</div></div>\",\"PeriodicalId\":23283,\"journal\":{\"name\":\"Transplantation and Cellular Therapy\",\"volume\":\"31 3\",\"pages\":\"Pages 159-165\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplantation and Cellular Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666636725000028\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation and Cellular Therapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666636725000028","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Reduced Chimeric Antigen Receptor T Cell Expansion Postinfusion Is Associated with Poor Survival in Patients with Large B Cell Lymphoma after Two or More Therapies
CD19-directed chimeric antigen receptor T cell (CAR-T) therapy is now standard of care for relapsed/refractory large B cell non-Hodgkin lymphoma. Despite good overall response rates, many patients still experience disease progression and therefore it is important to predict those at risk of relapse following CAR-T therapy. We performed a prospective study using a flow cytometry assay at a single treatment center to assess early CAR T cell expansion in vivo 6 to 9 days after CAR T cell infusion. Early CAR T cell expansion was used in conjunction with additional clinical risk factors to identify those at greater risk of relapse or treatment failure. Forty-four patients treated with commercial CD19-directed CAR-T therapy were included in the study, with a median follow-up of 306 days. CAR T cell expansion of >30 cells/μL was associated with a lower risk of disease progression or death (hazard ratio, 0.34; P = .048), but did not correlate with the risk of death alone. Patients who had poor early CAR T cell expansion (<30 cells/μL) in addition to high lactate dehydrogenase (LDH) had significantly lower median progression-free survival and overall survival. High LDH level alone was not a statistically significant risk factor for death or disease progression, and thus the interaction between CAR T cell expansion and this clinical risk factor may be important in predicting response. The mean CAR T cell count was higher in patients with grade 2 to 4 cytokine release syndrome (CRS) compared to those with grade 0 to 1 CRS (54.9 cells/μL versus 25.5 cells/μL; P = .01). The methodology of this assay is easily reproducible outside of a clinical trial, allowing for real-life implementation in clinical settings. This study suggests that early assessment of CAR T cell expansion can assist in identifying patients with poor overall survival who may benefit from early intervention or more intensive monitoring.