Transplantation and Cellular Therapy最新文献

{"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}

{"title":"Engraft: A Collaborative Learning Health Network for Enhanced Transplant and Cellular Therapy Outcomes","authors":"Christopher E. Dandoy ,&nbsp;Jeffery J. Auletta ,&nbsp;Priscila Badia ,&nbsp;Alan Bidgoli ,&nbsp;Nancy M. Daraiseh ,&nbsp;Anna M. DeSalvo ,&nbsp;Javier Diaz ,&nbsp;Stella M. Davies ,&nbsp;Kathleen Demmel ,&nbsp;Eleanor Cook ,&nbsp;John A. Craddock ,&nbsp;John Huber ,&nbsp;Megan Sampson ,&nbsp;Taylor J. Fitch ,&nbsp;Karis French ,&nbsp;Sonata Jodele ,&nbsp;Samantha M. Jaglowski ,&nbsp;Malika A. Kapadia ,&nbsp;Nandita Khera ,&nbsp;Georgia R. Kent ,&nbsp;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}

{"title":"Donor Type Does Not Impact Late Graft Failure Following Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis","authors":"Cindy Lynn Hickey ,&nbsp;Mei-Jie Zhang ,&nbsp;Mariam Allbee-Johnson ,&nbsp;Rizwan Romee ,&nbsp;Navneet S. Majhail ,&nbsp;Monzr M. Al Malki ,&nbsp;Joseph H. Antin ,&nbsp;Cara L. Benjamin ,&nbsp;Christopher Bredeson ,&nbsp;Saurabh Chhabra ,&nbsp;Michael R. Grunwald ,&nbsp;Yoshihiro Inamoto ,&nbsp;Christopher G. Kanakry ,&nbsp;Filippo Milano ,&nbsp;Robert J. Soiffer ,&nbsp;Scott R. Solomon ,&nbsp;Stephen R. Spellman ,&nbsp;Claudio G. Brunstein ,&nbsp;Corey Cutler","doi":"10.1016/j.jtct.2024.12.021","DOIUrl":"10.1016/j.jtct.2024.12.021","url":null,"abstract":"<div><h3>Background</h3><div>Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12% to 20% in haplo-HCT recipients using PTCy. The objective of this study was to determine whether donor type influenced the risk of late graft failure following reduced-intensity conditioning (RIC) HCT using PTCy-based GVHD prophylaxis.</div></div><div><h3>Study Design</h3><div>A retrospective cohort analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database among adult patients who underwent first RIC haplo or 8/8 matched unrelated donor (MUD) HCT between 2011 and 2018 for acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) with PTCy GVHD prophylaxis. The primary outcome was incidence of late graft failure, defined as secondary graft loss in the absence of relapse or poor graft function requiring a cellular therapy intervention.</div></div><div><h3>Results</h3><div>A total of 1336 patients met the eligibility criteria (1151 haplo, 185 MUD). Patients in the MUD group were older (65 vs. 61 years), less ethnically diverse (95% vs. 72% White), received fewer bone marrow grafts (45% vs. 16%), and had younger donors (median age, 28 vs. 37 years old). Conditioning regimens were predominately fludarabine, cyclophosphamide, and total body irradiation (TBI; 87% haplo and 38% MUD). At 2 years, the adjusted probabilities of late graft failure for the haplo group was 6.5% (95% confidence interval [CI], 5.2-8.0) versus 5.9% (95% CI, 2.7%–10.9%) for the MUD group (<em>P</em> = .79). Multivariate analysis for risk factors associated with late graft failure found associations with a diagnosis of MDS (HR, 1.98; 95% CI, 1.22–3.20; <em>P</em> = .005), and earlier year of HCT (2015–2018 vs. 2011–2014; HR, 0.39; 95% CI, 0.24-0.64; <em>P</em> = .0002). A post-hoc sensitivity analysis was performed to evaluate the effect of donor age and use of peripheral blood stem cell (PBSC) grafts. Graft failure did not differ between haplo and MUD HCT (HR, 1.19; <em>P</em> = .67) when adjusted for donor age nor when restricted to PBSC grafts only (HR, 0.85; <em>P</em> = .70).</div></div><div><h3>Conclusion</h3><div>In this registry-based analysis of patients undergoing RIC HCT for AML, ALL, or MDS using GVHD prophylaxis with PTCy, there was no significant difference in late graft failure rates between haplo and MUD donors. Overall rates of late graft failure were high.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 174.e1-174.e12"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928471","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}

{"title":"Tumor-Infiltrating Lymphocyte Therapy: A New Frontier","authors":"Diane Tseng ,&nbsp;Sylvia Lee","doi":"10.1016/j.jtct.2024.11.014","DOIUrl":"10.1016/j.jtct.2024.11.014","url":null,"abstract":"<div><div>In recent years, the successful use of tumor-infiltrating lymphocyte (TIL) therapy to treat melanoma not only culminated in a landmark Food and Drug Administration approval, but has also fueled the emergence of a new, rapidly growing field in TIL cellular immunotherapy surrounding novel enhancements in TIL design, refined manufacturing strategies to enrich for more potent TIL populations, as well as numerous clinical trials now investigating TIL therapy in additional solid tumor types beyond melanoma. This review provides a summary of the latest advances in TIL therapy and what lies ahead for the field. The first section explores several solid cancers that demonstrate the greatest potential for future indications of TIL therapy. The second section provides insight into the promising innovations for designing the next generation of TIL with greater specificity, persistence, safety, and function.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages S599-S609"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610673","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}

{"title":"Incidence, Risk Factors, and Outcomes of BK Hemorrhagic Cystitis in Hematopoietic Stem Cell Transplantation From HLA-Matched and Haploidentical Donors With Post-Transplant Cyclophosphamide","authors":"Pedro Chorão ,&nbsp;Marta Villalba ,&nbsp;Aitana Balaguer-Roselló ,&nbsp;Juan Montoro ,&nbsp;Pablo Granados ,&nbsp;Carmen Gilabert ,&nbsp;Francisca Panadero ,&nbsp;André Airosa Pardal ,&nbsp;Eva María González ,&nbsp;Santiago de Cossio ,&nbsp;Rafael Benavente ,&nbsp;María Dolores Gómez ,&nbsp;Inés Gómez ,&nbsp;Pilar Solves ,&nbsp;Marta Santiago ,&nbsp;Pedro Asensi ,&nbsp;Pilar Lloret ,&nbsp;Juan Eiris ,&nbsp;David Martínez ,&nbsp;Alberto Louro ,&nbsp;Jaime Sanz","doi":"10.1016/j.jtct.2024.12.006","DOIUrl":"10.1016/j.jtct.2024.12.006","url":null,"abstract":"<div><div>BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes. This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis. Furthermore, we analyze risk factors for BK-HC and its impact on renal function and transplant outcomes. Retrospective analysis of BK-HC episodes in patients undergoing HSCT from 167 MSD, 129 MUD and 103 HAPLO from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity, and mesna was used prophylactically with PTCy. The incidence of grade 2-4 BK-HC was 23%, with a higher prevalence of grades 3-4 in HAPLO (19%), compared to MSD (11%) and MUD (8%) recipients (<em>P</em> = .02). BK-HC was diagnosed at a median of 29 days after HSCT and symp toms persisted for a median of 27 days, with longer duration in grade 3-4 cases (<em>P</em> = .02). Additionally, higher grades were associated with a greater transfusion burden (<em>P</em> &lt; .001). JC virus coinfection was detected in 24%, and cytomegalovirus viruria in 17%, which was not treated. BK antiviral treatment beyond supportive care was used in only two patients, while antibacterial treatments were prescribed in 28% for urinary symptoms and in 57% for concomitant infections in other sites. Younger age and HAPLO donors were significant risk factors for developing higher-grade BK-HC. No interaction was seen between age and conditioning intensity. Importantly, BK-HC did not significantly impact overall survival or graft-versus-host disease-free relapse-free survival as a time-dependent variable, as well as non-relapse mortality. Furthermore, BK-HC patients maintained stable creatinine renal clearance at 1-year post-transplant. BK-HC is a relatively early frequent complication in allogeneic HSCT with PTCy, especially in HAPLO recipients, with symptoms typically lasting a median of three weeks. Supportive care remains the mainstay of treatment, while specific antiviral treatments are rarely needed. The role of cidofovir and concomitant CMV viruria treatment are yet to be established. Our findings suggest that BK-HC does not significantly impact transplant outcomes and renal function.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 182.e1-182.e11"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865545","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}

{"title":"Impact of Underlying Disease and Total Body Irradiation on the Incidence of Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation","authors":"Robert Puckrin ,&nbsp;Megan Kinzel ,&nbsp;Douglas Stewart ,&nbsp;Ahsan Chaudhry ,&nbsp;Kareem Jamani ,&nbsp;Jan Storek","doi":"10.1016/j.jtct.2024.12.024","DOIUrl":"10.1016/j.jtct.2024.12.024","url":null,"abstract":"<div><div>Multiple factors have been described to influence the risk of acute or chronic graft-versus-host disease (aGVHD or cGVHD) after allogeneic hematopoietic cell transplantation (HCT), including underlying chronic myeloid leukemia (CML) and high-dose total body irradiation (TBI). However, the impact of the underlying disease or low-dose TBI on the risk of GVHD in the modern era has not been determined. The objective of this study was to determine risk factors for GVHD in the modern era in the setting of antithymocyte globulin (ATG)-based GVHD prophylaxis. This retrospective study included 1219 patients with hematologic malignancy who underwent first peripheral blood allogeneic HCT using myeloablative fludarabine and busulfan conditioning ± low-dose total body irradiation, along with ATG, cyclosporine, and methotrexate as GVHD prophylaxis. The adjusted cumulative incidence of GVHD was compared between patient subgroups using multivariable competing risks regression. When disregarding the underlying disease, risk factors for grade 2-4 aGVHD were donor type other than matched sibling donor (non-MSD) and lack of low-dose TBI (non-TBI). Risk factors for grade 3-4 aGVHD were non-MSD, non-TBI, and CMV donor negative/recipient positive serostatus (D-R+). Risk factors for moderate-severe cGVHD were ≤9/10 HLA match, non-male/male donor/recipient sex, and non-TBI. In models including the underlying disease, additional significant risk factors were chronic lymphocytic leukemia (CLL) for grade 2 to 4 aGVHD (sub-hazard ratio over acute myeloid leukemia [SHR] 3.16, 95% CI 1.97-5.08, <em>P</em> &lt; .001); CLL and acute lymphoblastic leukemia (ALL) for grade 3-4 aGVHD (SHR for CLL 3.54, 95% CI 1.54-8.17, <em>P</em> = .003 and SHR for ALL 2.26, 95% CI 1.26-4.04, <em>P =</em> .006); and myelofibrosis (MF) for moderate-severe cGVHD (SHR 2.14, 95 CI 1.34-3.41, <em>P =</em> .001). In the modern era when using ATG for GVHD prophylaxis, newly identified risk factors include CLL and non-TBI for grade 2-4 aGVHD; CLL, ALL, and non-TBI for grade 3-4 aGVHD; and MF and non-TBI for moderate-severe cGVHD. These findings, if confirmed in a separate cohort, should be taken into consideration when tailoring the prophylaxis and monitoring of GVHD.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 176.e1-176.e8"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966616","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}

{"title":"The Cure of Thalassemia and the Angst of a Junior Attending","authors":"Keith M. Sullivan ,&nbsp;Jean E. Sanders","doi":"10.1016/j.jtct.2025.02.006","DOIUrl":"10.1016/j.jtct.2025.02.006","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 3","pages":"Pages 113-117"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511133","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}

{"title":"Tisagenlecleucel in Practice: Real-World Lessons in Pediatric and Young Adult B-ALL.","authors":"Kevin O McNerney, Liora M Schultz","doi":"10.1016/j.jtct.2025.02.016","DOIUrl":"10.1016/j.jtct.2025.02.016","url":null,"abstract":"<p><p>The global multi-institutional registration trial (ELIANA) of CD19.41BB.zeta chimeric antigen receptor (CAR) T cell therapy forged the path to the first FDA-approved CAR T product, tisagenlecleucel. Since its approval, extensive post-market experience with CAR T cells in children and young adults has amassed, allowing several multi-institutional efforts to leverage real-world data. Real-world data has validated clinical trial findings and provided insights into CAR T-cell use in patient groups not included in early clinical trials, such as children <3 years, patients with active CNS and isolated extramedullary disease, and patients treated in first relapse. Data from multi-centered consortia has also identified cohorts who experienced inferior outcomes post-tisagenlecleucel, informing high-risk groups for whom further treatment optimization is needed, and delineating treatment variables, such as CAR T cell dose and lymphodepleting chemotherapy pharmacokinetics, that impact outcomes. In this early stage of CAR T-cell therapies, real-world experience provides an increasingly rich data reservoir and an invaluable resource to investigate and address clinical gaps for CAR T recipients. This review highlights key insights gained from post-market studies that have informed clinical use of CAR T-cell therapy for children and young adults with B-ALL.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493845","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}

{"title":"Infections in Patients with Solid Tumors Undergoing Adoptive Cellular Therapy.","authors":"Viswatej Avutu, Jumanah N Algazaq, Kenneth Seier, Rhoena Desir-Camille, Li-Xuan Qin, Olayode Babatunde, Prasad S Adusumilli, Christopher A Klebanoff, Ritesh R Kotecha, Alexander N Shoushtari, Susan Slovin, Allison Betof Warner, Jae H Park, Adam J Schoenfeld, Roisin O'Cearbhaill, Sandra D'Angelo, Susan K Seo","doi":"10.1016/j.jtct.2025.02.017","DOIUrl":"10.1016/j.jtct.2025.02.017","url":null,"abstract":"<p><p>Adoptive cellular therapy (ACT) is an increasingly widely used treatment approach for malignancy. While infectious complications of ACT have been well described in patients with hematologic malignancies, limited data are available on the epidemiology of infections in patients with solid tumors. The purpose of this study was to describe the epidemiology of infections occurring within the first 180 days in adult patients with solid tumors treated with ACT and to identify risk factors predisposing these patients to infection. Data on 132 adult patients with solid tumors undergoing ACT between August 2014 and November 2021 at Memorial Sloan Kettering Cancer Center were collected. Infections were documented from the day of ACT infusion through day 180 postinfusion. Overall, 28 of 132 patients (21.2%) experienced 33 infections within the first 30 days of ACT, and 17 of 131 surviving patients (13%) were diagnosed with 24 infections between day 31 and day 180. Infection-related mortality was low. The majority of infections were bacterial. While male gender, older age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) at time of ACT infusion, tocilizumab receipt, and cytokine release syndrome treated with tocilizumab were associated with shorter time to first infection on univariable analysis, only ECOG PS and tocilizumab receipt remained independent risk factors in the multivariable analysis. The proportion of patients with solid tumors experiencing early or late infections after ACT was lower compared to that reported among patients with B cell malignancies after chimeric antigen receptor T cell therapy. Most observed infections were primarily bacterial with low infection-related mortality; the incidence of viral and fungal infections was low. Based on the low frequency and timing of infections relative to neutropenia, antibacterial and antifungal prophylaxis are not likely to be beneficial. ECOG PS ≥2 and tocilizumab receipt were identified as significant predictors for infection after ACT, likely signaling an individual's debilitated state that predisposes to infection. Additional work to parse out confounders is needed to better identify risk factors for infection.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493836","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}

{"title":"Awakening from REMS: ASTCT 80/20 Ongoing Recommendations for Safe Use of Chimeric Antigen Receptor T Cells.","authors":"Frederick L Locke, Zahra Mahmoudjafari, Partow Kebriaei, Rebecca A Gardner, Matthew J Frigault, Noelle V Frey, Krishna V Komanduri, Miguel-Angel Perales, Sarah Nikiforow","doi":"10.1016/j.jtct.2025.02.009","DOIUrl":"10.1016/j.jtct.2025.02.009","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The first 6 chimeric antigen receptor T cell (CAR-T) therapies approved in the United States have Risk Evaluation Mitigation Strategies (REMS) programs mandated by the US Food and Drug Administration (FDA). REMS programs aim to ensure the safe use of CAR-T therapy through timely recognition and management of unique severe risks and toxicities that cannot be mitigated by labeling alone, such as cytokine release syndrome and neurotoxicity syndromes. At the launch of each of the first 6 products, CAR-T REMS programs mandated product-specific education and training for clinical staff, patients, and caregivers; adequate access to medications to treat expected toxicities; and reporting of toxicities either to the product manufacturer or to the FDA. Each manufacturer ensures that treatment centers comply with the REMS program for their individual product in different ways, involving time-consuming and often redundant training, testing, and audits. The American Society for Transplantation and Cellular Therapy (ASTCT) 80/20 Subcommittee convened its second workshop in June 2023, inviting approximately 70 cellular therapy stakeholders to discuss whether safety and quality workflows embedded in existing resources within the cellular therapy field could replace FDA-mandated and company-monitored REMS programs. Attendees were clinicians at large academic medical centers experienced in cellular therapy, regulators, members of accrediting bodies and professional societies, and manufacturers of immune effector cell (IEC) therapies at multiple stages of development. Discussion centered on (1) educational requirements for safe delivery and management, (2) goals and mechanisms for data reporting and to whom, and (3) what entities should oversee these quality safeguards around CAR-T administration and management. Broad support was voiced for (1) conducting training programs administered by treatment centers and/or professional societies to replace manufacturers' product training; (2) reporting standardized data points into a central, accessible repository for tracking of safety trends and identification of new signals; and (3) enabling accrediting bodies to attest to programs' quality and ongoing compliance with field safety expectations, thereby replacing intensive manufacturer initial evaluation and ongoing REMS audits. The strong consensus of the second multidisciplinary ASTCT 80/20 Workshop was that such measures would allow elimination, or at least significant reduction and simplification, of current CAR-T REMS programs. Development of educational resources and funding for data reporting outside of a mandated REMS structure were identified as critical, particularly to support treatment centers new to cellular therapy, as were ongoing collaborations with FDA and manufacturers. These consensus recommendations were shared with the FDA at the Cell Therapy Liaison Meeting and in multiple professional society meetings and other public forums with regulators, ma","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426356","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}