Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.04.015
Justin J. Lievense , Cynthia Nijenhuis , Inge Jedema , Arendien Jonker-Hoogerkamp , Justin T. Moyers , Omid Hamid , Jos H. Beijnen , John B.A.G. Haanen , Bastiaan Nuijen
Tumor-infiltrating lymphocyte (TIL) medicinal products (MPs) show promise for treating solid tumors, especially metastatic melanoma, in the clinical trial setting. Through these studies, TIL developers have gained an immunological perspective into the mechanism of action (MoA) and infusion product characteristics that influence clinical response. However, to reach marketing authorization for any of the TIL MPs, it will be beneficial to gain a pharmaceutical (process) development perspective as well, from which control of the TIL MPs manufacturing process can be demonstrated and a suitable control strategy can be developed. To do this, a well-defined TIL MP must be established. Defining and optimizing MPs from a pharmaceutical perspective is done by identifying and improving product characteristics or quality attributes (QAs) thought to impact safety and efficacy. Through awareness of the QAs relevant to TIL MPs and considering them throughout pharmaceutical development, improvements and changes can be validated. This approach to pharmaceutical development is part of the quality-by-design workflow, of which this review tackles the first steps. Here, the QAs are structured within a quality target product profile (QTPP), and the corresponding regulatory expectations are considered, spanning quantity, identity, purity, microbiological assays, and biological activity. Based on the regulatory expectations and available literature, the (critical) QAs and points of consideration are proposed when developing TIL MPs. The active pharmaceutical ingredient of the TIL MP is defined as the CD45+CD3+ cells. By analyzing identity attributes correlated to clinical efficacy, four broadly applicable in vivo functionalities associated with TIL MPs MoA and clinical effectiveness are described: tumor recognition, cytotoxic capacity, tumor homing, and persistence. How these in vivo functionalities are quantified in potency assays and the limitations of their methods/readouts are also discussed. The QTPP is a foundation for developing a robust, substantiated control strategy for regulatory approval and increasing patient access. Harmonizing TIL MP development under a unified QTPP applicable in different settings could also facilitate comparisons and, therefore, the development of safer and more efficacious TIL MP variations.
{"title":"Defining the Quality Attributes for Tumor-Infiltrating Lymphocyte Medicinal Products","authors":"Justin J. Lievense , Cynthia Nijenhuis , Inge Jedema , Arendien Jonker-Hoogerkamp , Justin T. Moyers , Omid Hamid , Jos H. Beijnen , John B.A.G. Haanen , Bastiaan Nuijen","doi":"10.1016/j.jtct.2024.04.015","DOIUrl":"10.1016/j.jtct.2024.04.015","url":null,"abstract":"<div><div>Tumor-infiltrating lymphocyte (TIL) medicinal products (MPs) show promise for treating solid tumors, especially metastatic melanoma, in the clinical trial setting. Through these studies, TIL developers have gained an immunological perspective into the mechanism of action (MoA) and infusion product characteristics that influence clinical response. However, to reach marketing authorization for any of the TIL MPs, it will be beneficial to gain a pharmaceutical (process) development perspective as well, from which control of the TIL MPs manufacturing process can be demonstrated and a suitable control strategy can be developed. To do this, a well-defined TIL MP must be established. Defining and optimizing MPs from a pharmaceutical perspective is done by identifying and improving product characteristics or quality attributes (QAs) thought to impact safety and efficacy. Through awareness of the QAs relevant to TIL MPs and considering them throughout pharmaceutical development, improvements and changes can be validated. This approach to pharmaceutical development is part of the quality-by-design workflow, of which this review tackles the first steps. Here, the QAs are structured within a quality target product profile (QTPP), and the corresponding regulatory expectations are considered, spanning quantity, identity, purity, microbiological assays, and biological activity. Based on the regulatory expectations and available literature, the (critical) QAs and points of consideration are proposed when developing TIL MPs. The active pharmaceutical ingredient of the TIL MP is defined as the CD45+CD3+ cells. By analyzing identity attributes correlated to clinical efficacy, four broadly applicable <em>in vivo</em> functionalities associated with TIL MPs MoA and clinical effectiveness are described: tumor recognition, cytotoxic capacity, tumor homing, and persistence. How these <em>in vivo</em> functionalities are quantified in potency assays and the limitations of their methods/readouts are also discussed. The QTPP is a foundation for developing a robust, substantiated control strategy for regulatory approval and increasing patient access. Harmonizing TIL MP development under a unified QTPP applicable in different settings could also facilitate comparisons and, therefore, the development of safer and more efficacious TIL MP variations.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S610-S625"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2025.01.001
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
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.
{"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":"10.1016/j.jtct.2025.01.001","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":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.11.017
Alexander N. Shoushtari , Daniel J. Powell
Lifileucel, the first solid tumor adoptive tumor infiltrating lymphocyte (TIL) therapy product to receive regulatory approval in advanced melanoma, represents a critical achievement in the pursuit of improving outcomes using cellular therapies in patients with solid tumors. This review traces the development of adoptive TIL therapy from the initial human studies in melanoma, through recent advances in studies of other solid tumors, and previews ongoing and future areas for preclinical and clinical advances to improve upon this novel therapeutic strategy.
{"title":"Tumor-Infiltrating Lymphocyte Therapy for Melanoma and Other Solid Tumors: Looking Back, Yet Moving Forward","authors":"Alexander N. Shoushtari , Daniel J. Powell","doi":"10.1016/j.jtct.2024.11.017","DOIUrl":"10.1016/j.jtct.2024.11.017","url":null,"abstract":"<div><div>Lifileucel, the first solid tumor adoptive tumor infiltrating lymphocyte (TIL) therapy product to receive regulatory approval in advanced melanoma, represents a critical achievement in the pursuit of improving outcomes using cellular therapies in patients with solid tumors. This review traces the development of adoptive TIL therapy from the initial human studies in melanoma, through recent advances in studies of other solid tumors, and previews ongoing and future areas for preclinical and clinical advances to improve upon this novel therapeutic strategy.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S581-S590"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/S2666-6367(25)01017-6
{"title":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S2666-6367(25)01017-6","DOIUrl":"10.1016/S2666-6367(25)01017-6","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A3"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.016
Enass H Raffa , Taylor M Harris , Chane Choed-Amphai , Melanie Kirby-Allen , Isaac Odame , Muhammad Ali , Joerg Krueger , Karin G Hermans , Soumitra Tole , Jennifer Seelisch , Robert J Klaassen , Lesleigh Abbott , Yogi Raj Chopra , Donna A Wall , Kuang-Yueh Chiang
Allogeneic hematopoietic stem cell transplantation is challenging for patients with transfusion-dependent thalassemia who have experienced iron overload and received chronic transfusion support. A transplantation strategy including a reduced-intensity preparative regimen and tailored immunosuppression to support donor engraftment and prevent graft-versus-host disease (GVHD) was developed for this population. The combination of a pretransplantation immunosuppression phase with reduced dosing of fludarabine/prednisone, a treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/antithymocyte globulin was tested. In the ThalFAbS trial, a prospective pilot trial (ClinicalTrials.gov NCT05426252) of a transplantation strategy designed for higher-risk patients with transfusion-dependent thalassemia, 12 pediatric patients (4 with alpha thalassemia, 8 with beta thalassemia) were treated with this strategy. Descriptive statistics were used to characterize transplantation outcomes and immune recovery. With a median follow-up of 12 months (range, 4 to 26 months) post-transplantation, all 12 patients had prompt and durable trilineage donor engraftment with low transplantation-related morbidity and acute GVHD and are alive without transfusion support at the time of this report. GVHD was limited to 1 patient with skin-only grade II acute GVHD and 3 patients with limited oral chronic GVHD. Early hematologic and immunologic recovery was achieved, with low rates of transfusion support and infection. Neutrophil recovery occurred at a median of 18 days (range, 15 to 24 days), and platelet recovery occurred at a median of 18 days (range, 12 to 36 days). No patients experienced veno-occlusive disease, transplantation-associated thrombotic microangiopathy, or sepsis. This platform was sufficient to support haploidentical donor transplantation in 2 patients. The ThalFAbS approach is tailored to meet the unique needs of transfusion-dependent thalassemia patients. Delivery of this novel regimen is feasible, and it shows excellent early engraftment and transplantation outcomes. Further follow-up of this cohort and expansion of patient numbers is needed before the findings can be generalized, but early experience is promising.
{"title":"Early Engraftment and Immune Kinetics Following Allogeneic Transplant Using a Novel Reduced-Toxicity Transplant Strategy in Children/Adolescents with High-Risk Transfusion-Dependent Thalassemia: Early Results of the ThalFAbS Trial","authors":"Enass H Raffa , Taylor M Harris , Chane Choed-Amphai , Melanie Kirby-Allen , Isaac Odame , Muhammad Ali , Joerg Krueger , Karin G Hermans , Soumitra Tole , Jennifer Seelisch , Robert J Klaassen , Lesleigh Abbott , Yogi Raj Chopra , Donna A Wall , Kuang-Yueh Chiang","doi":"10.1016/j.jtct.2024.12.016","DOIUrl":"10.1016/j.jtct.2024.12.016","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell transplantation is challenging for patients with transfusion-dependent thalassemia who have experienced iron overload and received chronic transfusion support. A transplantation strategy including a reduced-intensity preparative regimen and tailored immunosuppression to support donor engraftment and prevent graft-versus-host disease (GVHD) was developed for this population. The combination of a pretransplantation immunosuppression phase with reduced dosing of fludarabine/prednisone, a treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/antithymocyte globulin was tested. In the ThalFAbS trial, a prospective pilot trial (ClinicalTrials.gov NCT05426252) of a transplantation strategy designed for higher-risk patients with transfusion-dependent thalassemia, 12 pediatric patients (4 with alpha thalassemia, 8 with beta thalassemia) were treated with this strategy. Descriptive statistics were used to characterize transplantation outcomes and immune recovery. With a median follow-up of 12 months (range, 4 to 26 months) post-transplantation, all 12 patients had prompt and durable trilineage donor engraftment with low transplantation-related morbidity and acute GVHD and are alive without transfusion support at the time of this report. GVHD was limited to 1 patient with skin-only grade II acute GVHD and 3 patients with limited oral chronic GVHD. Early hematologic and immunologic recovery was achieved, with low rates of transfusion support and infection. Neutrophil recovery occurred at a median of 18 days (range, 15 to 24 days), and platelet recovery occurred at a median of 18 days (range, 12 to 36 days). No patients experienced veno-occlusive disease, transplantation-associated thrombotic microangiopathy, or sepsis. This platform was sufficient to support haploidentical donor transplantation in 2 patients. The ThalFAbS approach is tailored to meet the unique needs of transfusion-dependent thalassemia patients. Delivery of this novel regimen is feasible, and it shows excellent early engraftment and transplantation outcomes. Further follow-up of this cohort and expansion of patient numbers is needed before the findings can be generalized, but early experience is promising.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 180.e1-180.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.023
Oren Pasvolsky , Curtis Marcoux , Zhongya Wang , Denái R. Milton , Babar Pal , Mark R. Tanner , Qaiser Bashir , Samer Srour , Neeraj Saini , Paul Lin , Jeremy Ramdial , Yago Nieto , Guilin Tang , Naureen Syed , Yosra Aljawai , Hans C. Lee , Krina K. Patel , Melody R. Becnel , Christine Ye , Partow Kebriaei , Muzaffar H. Qazilbash
Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification. A total of 1000 SRMM patients were included, with a median age of 61 years (range 25 to 83), and 61% were male (n = 612). The most common induction regimens were bortezomib/lenalidomide/dexamethasone (VRD; n = 398, 40%) and carfilzomib/lenalidomide/dexamethasone (KRD; n = 212, 21%), and the majority (87%) received single-agent melphalan as conditioning. After induction and before autoHCT, 16% and 57% achieved ≥complete response (CR) and ≥very good partial response (VGPR), respectively. At day 100 post autoHCT, 37% and 77% achieved ≥CR and ≥VGPR, respectively. Sixty-two percent and 89% of patients achieved ≥ CR and ≥VGPR as best response post-transplant. A minimal residual disease (MRD) negative response pre- and post-transplantation was achieved in 43% (401/936) and 64% (199/311) of patients, respectively. After a median follow-up of 42.1 months, the median progression-free survival (PFS) for the entire cohort was 68.3 months (95% CI 60.1 to 72.1), and the median overall survival (OS) was not reached (95% CI 102.3-not reached). The 5-year PFS and OS rates were 55% and 83%, respectively. In multivariable analysis, achieving MRD-negative CR prior to autoHCT (HR 0.65 [95% CI 0.44 to 0.97], P = .033) or as best response (0.52 [0.34 to 0.78], P = .002), and use of post-transplant maintenance (0.69 [0.52 to 0.93], P = .013) and lenalidomide-based combination maintenance (0.68 [0.48 to 0.96], P = .030) were associated with improved PFS, whereas use of an induction regimen other than KRD was associated with worse PFS (1.50 [1.04 to 2.17], P = .031). For OS, post-transplant maintenance (0.48 [0.32 to 0.70], P < .001) was associated with better survival in multivariable analysis, whereas R-ISS stage III, compared with stage I, (2.34 [1.01 to 5.43], P = .047) was associated with worse OS. Patients with SRMM who received upfront autoHCT had a median PFS of >5.5 years, and median OS was not reached. These results highlight the favorable outcomes with upfront autoHCT for patients with SRMM, serving as a benchmark for future therapeutic approaches in this subgroup of MM patients.
{"title":"Outcomes of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation","authors":"Oren Pasvolsky , Curtis Marcoux , Zhongya Wang , Denái R. Milton , Babar Pal , Mark R. Tanner , Qaiser Bashir , Samer Srour , Neeraj Saini , Paul Lin , Jeremy Ramdial , Yago Nieto , Guilin Tang , Naureen Syed , Yosra Aljawai , Hans C. Lee , Krina K. Patel , Melody R. Becnel , Christine Ye , Partow Kebriaei , Muzaffar H. Qazilbash","doi":"10.1016/j.jtct.2024.12.023","DOIUrl":"10.1016/j.jtct.2024.12.023","url":null,"abstract":"<div><div>Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification. A total of 1000 SRMM patients were included, with a median age of 61 years (range 25 to 83), and 61% were male (<em>n</em> = 612). The most common induction regimens were bortezomib/lenalidomide/dexamethasone (VRD; <em>n</em> = 398, 40%) and carfilzomib/lenalidomide/dexamethasone (KRD; <em>n</em> = 212, 21%), and the majority (87%) received single-agent melphalan as conditioning. After induction and before autoHCT, 16% and 57% achieved ≥complete response (CR) and ≥very good partial response (VGPR), respectively. At day 100 post autoHCT, 37% and 77% achieved ≥CR and ≥VGPR, respectively. Sixty-two percent and 89% of patients achieved ≥ CR and ≥VGPR as best response post-transplant. A minimal residual disease (MRD) negative response pre- and post-transplantation was achieved in 43% (401/936) and 64% (199/311) of patients, respectively. After a median follow-up of 42.1 months, the median progression-free survival (PFS) for the entire cohort was 68.3 months (95% CI 60.1 to 72.1), and the median overall survival (OS) was not reached (95% CI 102.3-not reached). The 5-year PFS and OS rates were 55% and 83%, respectively. In multivariable analysis, achieving MRD-negative CR prior to autoHCT (HR 0.65 [95% CI 0.44 to 0.97], <em>P</em> = .033) or as best response (0.52 [0.34 to 0.78], <em>P</em> = .002), and use of post-transplant maintenance (0.69 [0.52 to 0.93], <em>P</em> = .013) and lenalidomide-based combination maintenance (0.68 [0.48 to 0.96], <em>P</em> = .030) were associated with improved PFS, whereas use of an induction regimen other than KRD was associated with worse PFS (1.50 [1.04 to 2.17], <em>P</em> = .031). For OS, post-transplant maintenance (0.48 [0.32 to 0.70], <em>P</em> < .001) was associated with better survival in multivariable analysis, whereas R-ISS stage III, compared with stage I, (2.34 [1.01 to 5.43], <em>P</em> = .047) was associated with worse OS. Patients with SRMM who received upfront autoHCT had a median PFS of >5.5 years, and median OS was not reached. These results highlight the favorable outcomes with upfront autoHCT for patients with SRMM, serving as a benchmark for future therapeutic approaches in this subgroup of MM patients.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 166.e1-166.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/S2666-6367(25)01026-7
{"title":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(25)01026-7","DOIUrl":"10.1016/S2666-6367(25)01026-7","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Page A1"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2025.02.007
Vinodh Pillai
{"title":"CAR-T — The Slow and the Spurious","authors":"Vinodh Pillai","doi":"10.1016/j.jtct.2025.02.007","DOIUrl":"10.1016/j.jtct.2025.02.007","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 121-122"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jtct.2024.12.017
Christopher E. Dandoy , Jeffery J. Auletta , Priscila Badia , Alan Bidgoli , Nancy M. Daraiseh , Anna M. DeSalvo , Javier Diaz , Stella M. Davies , Kathleen Demmel , Eleanor Cook , John A. Craddock , John Huber , Megan Sampson , Taylor J. Fitch , Karis French , Sonata Jodele , Samantha M. Jaglowski , Malika A. Kapadia , Nandita Khera , Georgia R. Kent , David Hartley
The Engraft Learning Health Network (LHN) aims to improve outcomes for patients undergoing transplant and cellular therapy (TCT) through a collaborative, data-driven approach. Engraft brings together diverse stakeholders, including clinicians, patients, caregivers, and institutions, to standardize best practices and accelerate the dissemination of innovations in TCT care. By establishing a multicenter, real-world clinical registry focused on rapid-cycle quality improvement (QI) and implementation research, Engraft seeks to reduce variability in clinical practice to improve TCT outcomes across centers. Initial efforts have centered on developing QI toolkits, sharing de-identified patient data, and building consensus around best practices to reduce non-relapse mortality and improve survivorship. A distinctive feature of Engraft is its commitment to engaging patients and caregivers as equal partners in the network's direction. This manuscript outlines the network's design, early successes, and future goals.
{"title":"Engraft: A Collaborative Learning Health Network for Enhanced Transplant and Cellular Therapy Outcomes","authors":"Christopher E. Dandoy , Jeffery J. Auletta , Priscila Badia , Alan Bidgoli , Nancy M. Daraiseh , Anna M. DeSalvo , Javier Diaz , Stella M. Davies , Kathleen Demmel , Eleanor Cook , John A. Craddock , John Huber , Megan Sampson , Taylor J. Fitch , Karis French , Sonata Jodele , Samantha M. Jaglowski , Malika A. Kapadia , Nandita Khera , Georgia R. Kent , David Hartley","doi":"10.1016/j.jtct.2024.12.017","DOIUrl":"10.1016/j.jtct.2024.12.017","url":null,"abstract":"<div><div>The Engraft Learning Health Network (LHN) aims to improve outcomes for patients undergoing transplant and cellular therapy (TCT) through a collaborative, data-driven approach. Engraft brings together diverse stakeholders, including clinicians, patients, caregivers, and institutions, to standardize best practices and accelerate the dissemination of innovations in TCT care. By establishing a multicenter, real-world clinical registry focused on rapid-cycle quality improvement (QI) and implementation research, Engraft seeks to reduce variability in clinical practice to improve TCT outcomes across centers. Initial efforts have centered on developing QI toolkits, sharing de-identified patient data, and building consensus around best practices to reduce non-relapse mortality and improve survivorship. A distinctive feature of Engraft is its commitment to engaging patients and caregivers as equal partners in the network's direction. This manuscript outlines the network's design, early successes, and future goals.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 123-134"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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