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1.
Updated Indications for Immune Effector Cell Therapy: 2023 Guidelines from the American Society for Transplantation and Cellular Therapy
Kanate, A. S., Majhail, N., DeFilipp, Z. M., Dhakal, B., Dholaria, B., Hamilton, B., Herrera, A. F., Inamoto, Y., Jain, T., Perales, M. A., et al
Transplantation and cellular therapy. 2023
Abstract
The American Society for Transplantation and Cellular Therapy (ASTCT) published its guidelines on indications for autologous and allogeneic hematopoietic cell transplantation (HCT) and immune effector cell therapy (IECT) in 2020. Since then we have witnessed rapid advancements in the field of IECT, resulting in several new chimeric antigen receptor T-cell (CAR-T) products and disease indications being approved by the U.S. Food and Drug Administration (FDA). To keep abreast of these practice changes, the ASTCT Committee on Practice Guidelines commissioned a focused update covering CAR-T therapy indications. This brief manuscript presents updated ASTCT recommendations on indications for CAR-T therapy. Only FDA approved indications for CAR-T were recommended and categorized as "standard of care" (S), where indication is well defined and supported by evidence. The ASTCT will continue to periodically review these guidelines and update them as new evidence becomes available.
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2.
Paving the Road for CAR-Ts: ASTCT 80/20 Task Force consensus on challenges and solutions to improving efficiency of clinical center certification and maintenance of operations for commercially approved immune effector cell therapies
Nikiforow, S., Frigault, M. J., Frey, N. V., Gardner, R. A., Komanduri, K. V., Perales, M. A., Kebriaei, P., Warkentin, P. I., Pasquini, M., Aho, J. L., et al
Transplantation and cellular therapy. 2023
Abstract
As the number and type of regulatory authority-approved cellular therapies grow, clinical treatment centers face a heavy burden of duplicative documentation around initial qualification, ongoing auditing, and reporting-with overlapping requirements from each manufacturer to ensure safe use of their specific product, which in the United States are stipulated under individual Food and Drug Administration (FDA) Biologic License Applications (BLA). The American Society for Transplantation and Cellular Therapy (ASTCT) convened the 80/20 Taskforce to consider challenges and potential solutions to these issues. The taskforce proposed that 80% of manufacturers' requirements for onboarding and ongoing operations of commercially available products could be standardized and streamlined. Taskforce members interviewed dozens of stakeholders, including clinicians at large academic medical centers already utilizing commercial and investigational immune effector cell (IEC) products, regulators, members of accrediting bodies and professional cellular therapy societies, and manufacturers of IEC therapies for oncologic indications. In November 2021, the taskforce organized and led virtual discussions in a public forum and at a private ASTCT 80/20 workshop at the online AcCELLerate Forum, a cellular-therapy stakeholders' meeting organized by the ASTCT, the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR). At the workshop, approximately 60 stakeholders worked to identify and prioritize common challenges in onboarding and maintenance of operations at clinical sites for commercial FDA-approved and future IEC therapies and ways to streamline the process. It was agreed that standardization would improve efficiency of onboarding, allowing more cost-effective, sustainable growth of approved IEC therapies at treatment centers, and facilitate wider access while maintaining safety and clinical success. This early but extensive survey of stakeholders resulted in five overarching suggestions for both established and emerging treatment centers: 1. Eliminate duplication in accreditation and auditing of clinical sites; 2. Define expectations for education and management of CAR-T cell therapy toxicities to potentially replace product-specific REMS programs; 3. Streamline current REMS education, testing and data reporting; 4. Standardize IT platforms supporting enrollment, clinical site-to-manufacturer communication, and logistics of maintaining chain of identity/chain of custody across multiple transportation steps; 5. Encourage use of universal nomenclature by cell therapy manufacturers. Future discussions need to engage a broader range of stakeholders including administrators, pharmacists, nurses, data coordinators, surgeons, pathologists, and those developing promising cellular therapies for solid tumors, as well as teams from smaller academic or community cancer center settings. Continued collaboration with stakeholders outside of clinical sites will include accrediting bodies/auditors, established and emerging cell therapy companies, software developers, professional societies, and the patients who receive these therapies. Active dialogue with government regulators remains essential. Such joint efforts are critical as the number of IEC therapies for myriad oncologic and non-oncologic indications grows.
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3.
The EBMT Immune Effector Cell Nursing Guidelines on CAR-T Therapy: A Framework for Patient Care and Managing Common Toxicities
Ellard, R., Kenyon, M., Hutt, D., Aerts, E., de Ruijter, M., Chabannon, C., Mohty, M., Montoto, S., Wallhult, E., Murray, J.
Clinical hematology international. 2022;4(3):75-88
Abstract
Chimeric antigen receptor T-cell (CAR T) therapy is a new and rapidly developing field. Centers across the world are gaining more experience using these innovative anti-cancer treatments, transitioning from the 'bench' to the 'bedside', giving benefit to an increasing number of patients. For those with some refractory hematological malignancies, CAR-T may offer a treatment option that was not available a few years ago.CAR-T therapy is an immune effector cell and precision/personalized medicine treatment which is tailored to the individual patient and associated with a variety of unique adverse events and toxicities that necessitate specialist nursing/medical vigilance in an appropriate clinical setting. Subtle unrecognized signs and symptoms can result in rapid deterioration and, possibly, life threatening cardiorespiratory and/or neurological sequelae.These guidelines have been prepared for nurses working in cellular therapy in inpatient, outpatient and ambulatory settings. Many nurses will encounter cellular therapy recipients indirectly, during the referral process, following discharge, and when patients are repatriated back to local centers. The aim of these guidelines is to provide all nurses with a practice framework to enable recognition, monitoring and grading of CAR-T therapy-associated toxicities, and to support and nurse these highly complex patients with confidence.They have been developed under the auspices of several bodies of the European society for Blood and Marrow Transplantation (EBMT), by experienced health professionals, and will be a valuable resource to all practitioners working in cellular therapy.
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4.
[Role of allogeneic hematopoietic cell transplantation after anti-CD19 CAR T-cell treatment: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
Beauvais, D., Castilla-Llorente, C., Diral, E., Sirvent, A., Vandewiele, A., Baruchel, A., Yakoub-Agha, I., Yakouben, K.
Bulletin du cancer. 2022
Abstract
The role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR T- treatment cells in hematologic malignancies is currently controversial. Prolonged remissions after several years of follow-up suggest that there is a curative effect of CAR T-cells therapy, whereas allo-HCT was previously considered the only curative treatment in relapse situation. The aim of this harmonization workshop is to detail the existing data in the literature on the feasibility of allo-HCT after CAR T-cells and to propose to consider allograft in selected patients with B-acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). In B-ALL, various intrinsic factors (inherent to the patient, to the disease, to the type of CAR T-cells) and especially various post CAR T-cells criteria (early expansion kinetics, residual disease at D28, early loss of B-cell aplasia) should lead to consider performing allo-HCT before the occurrence of a relapse. In DLBCL, although there are risk factors for relapse at diagnosis and prior to CAR T-cells therapy, response assessed by PET-CT at three months is critical and allo-HCT cannot currently be recommended in cases of complete or partial remission. In any case, if the age is appropriate for allogeneic transplantation, HLA typing should be performed before CAR T-cells treatment in order not to delay the allo-HCT project if needed.
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5.
ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Diffuse Large B-cell Lymphoma after failure of Chimeric antigen receptor T cell therapy (CAR-T) therapy
Ahmed, N., Kumar, A., Kharfan-Dabaja, M. A., DeFilipp, Z., Herrera, A., Hashmi, S., Dholaria, B., Perales, M. A., Carpenter, P. A., Hamadani, M.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Chimeric antigen receptor T cell therapy (CAR-T) is a major advance in managing aggressive relapsed and/or refractory B-cell lymphomas; however, relapses are frequent and pose a major therapeutic challenge. There is substantial variability across transplant and cellular therapy programs in assessing and managing post-CAR-T failures. METHODS The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between August 2021 and October 2021, to determine the U.S. lymphoma and transplant and cellular therapy physicians' practice patterns for the detection and diagnosis of CAR-T failure, and management strategies for diffuse large B cell lymphoma (DLBCL) in this particular setting. RESULTS Email surveys were sent to 901 potential participants, of which 174 (19%) completed the survey. Responders were mainly White (51.2%), male (70.7%), and with >10 years of practice experience (51.2%). 87% of the responders were affiliated with university/teaching centers; 54.6% had general oncology practices and 45.4% had lymphoma-focused transplant/cellular therapy practices. The most common periods to perform surveillance scans were at 3 months and 12 months after CAR-T infusion. 88.5% of responders would often or always consider a biopsy to confirm relapse and 89% would routinely check for the persistence of the antigen targeted by the CAR (e.g. CD19 in the case of CD19 CAR-T). The most popular first salvage regimen for relapse or progression was an alternate CAR-T therapy (dual or alternate target) regardless of CD19 positivity. 27% of responders chose this regimen for CD19 positive relapse, while 31% of responders did so for CD19 negative relapse. 88.5% of responders favored consolidative allogeneic hematopoietic cell transplantation (alloHCT) after response to salvage, whereas 51.2% of physicians would consider autologous hematopoietic cell transplant (AHCT) in transplant naïve patients. CONCLUSIONS There is substantial cross-center variation in surveillance, diagnosis, and management of CAR-T failure. Prospective clinical trials evaluating novel agents in this setting are urgently needed to identify best management strategies.
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6.
ASTCT Clinical Practice recommendations for transplant and cellular therapies in multiple myeloma
Dhakal, B., Shah, N., Kansagra, A., Kumar, A., Lonial, S., Garfall, A., Cowan, A., Poudyal, B. S., Costello, C., Gay, F., et al
Transplantation and cellular therapy. 2022
Abstract
Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape. The American Society for Transplantation and Cellular Therapy (ASTCT) convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.
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7.
Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer
Ragoonanan, D., Khazal, S. J., Abdel-Azim, H., McCall, D., Cuglievan, B., Tambaro, F. P., Ahmad, A. H., Rowan, C. M., Gutierrez, C., Schadler, K., et al
Nature reviews. Clinical oncology. 2021
Abstract
Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.
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8.
[Follow-up logbook of patients receiving CAR T-cell therapy: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
Berquier, M., Cherel, L., Clerc Renaud, D., Hospital Gustems, C., Wallart Brejaud, A., Yakoub-Agha, I., Beauvais, D.
Bulletin du cancer. 2021
Abstract
In the attempt to harmonize practices and to create a national CAR T-cells patient follow-up care logbook, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) worked on the design of a common national care logbook during the eleventh annual workshops of practice harmonization. The purpose of this logbook was to explain the different phases of the treatment with CAR T-cells and to allow useful monitoring for the patient. This logbook can be also helpful for the different healthcare professionals involved in the patient care. This national logbook will provide important information to the patients undergoing CAR T-cell therapy. In addition to the information booklets already in use, the national logbook simplifies patient follow-up by recording various medical appointments and possible adverse events. This work has been based on tools that had already been put in place by different CAR T-cell centers. This national logbook represents a common "base" and is prepared in the form of index cards to be classified using dividers in a binder. Therefore, the national care logbook will be adaptable for local procedures and guidelines of each center.
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9.
[A standardized medical report template for CAR T-Cell therapy patients: Guidelines of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
Broussais, F., Vasseur, A., Karam, M., Chaillou, D., Pereira, M., Yakoub-Agha, I., Raus, N.
Bulletin du cancer. 2021
Abstract
Tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™) are the first representatives of a new class of gene therapies produced by ex-vivo genetic modification of human autologous T lymphocytes, now using viral vectors. In 2020, there are three independent CAR-T cell databases in France: DESCAR-T (database supported by LYSARC, GRAALL and the IFM), ProMISe (EBMT database) and ATIH (database of the Agence Technique de l'Information sur l'Hospitalisation). Only the EBMT database is common to France and the French-speaking countries that are members of the SFGM-TC. In 2019, a workshop was held to draft a manual for entering data specific to CAR-T cells in the EBMT ProMISe database. As a follow-up to this article, we present a medical report template containing all the data required to enter the data of patients treated with CAR-T in the EBMT registry, in the CRF of the DESCAR-T registry and in the ATIH registry. This document aims to improve the completeness and quality of the data while optimizing data entry time.
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10.
Management of Adults and Children receiving CAR T-cell therapy: 2021 Best Practice Recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)
Hayden, P. J., Roddie, C., Bader, P., Basak, G. W., Bonig, H., Bonini, C., Chabannon, C., Ciceri, F., Corbacioglu, S., Ellard, R., et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2021
Abstract
BACKGROUND Several commercial and academic autologous chimeric antigen receptor T-cell products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma, and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future. DESIGN EBMT-JACIE and the European Haematology association (EHA) proposed to draft best practice recommendations based on the current literature, to support healthcare professionals in delivering consistent, high-quality care in this rapidly moving field RESULTS Thirty-six CAR-T experts (medical; nursing; pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues. CONCLUSIONS We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for hematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.