Timely Leukapheresis May Interfere with the “Fitness” of Lymphocytes Collected for CAR-T Treatment in High Risk DLBCL Patients

The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (Cli...

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Published in:Cancers 2022-10, Vol.14 (21), p.5276
Main Authors: Farina, Mirko, Chiarini, Marco, Almici, Camillo, Accorsi Buttini, Eugenia, Zuccalà, Francesco, Piva, Simone, Volonghi, Irene, Poli, Loris, Bernardi, Simona, Colnaghi, Federica, Re, Federica, Leoni, Alessandro, Polverelli, Nicola, Turra, Alessandro, Morello, Enrico, Galvagni, Anna, Moratto, Daniele, Brugnoni, Duilio, Cattaneo, Chiara, Ferrari, Emilio, Bianchetti, Andrea, Malagola, Michele, Re, Alessandro, Russo, Domenico
Format: Article
Language:English
Subjects:
Antigens
Apheresis
Autografts
Care and treatment
CD4 antigen
CD8 antigen
Cell differentiation
Cell therapy
Chemotherapy
Chimeric antigen receptors
Disease
Fitness
Health aspects
Hematological diseases
Hematology
Infections
Leukapheresis
Leukemia
Lymphocytes
Lymphocytes T
Lymphoma
Lymphomas
Manufacturing
Methods
Patient outcomes
Patients
Stem cell transplantation
Stem cells
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Summary:The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials.gov: NCT05366569) is to improve our understanding of the lymphocyte harvest to maximize the quality of the CAR-T cell product. Of the 14 patients enrolled, 11 were diagnosed with DLBCL, 2 with PMBCL, and 1 with ALL. Five of 11 DLBCL patients met the criteria for “pre-emptive” Lymphocytes-apheresis (being at high risk of second relapse), and 6 were included in the standard-of-care Lymphocytes-apheresis group. Previous autologous stem cell transplantation (ASCT) and age were significantly different between the two groups. At the time of Lymphocyte-apheresis, patients in the “pre-emptive” group had more “fit” lymphocytes (higher CD4+/CD8+ ratio; higher naïve T cells levels) compared with standard group, probably due to the impact of ASCT. At the same time, also being older than 60 years results in a more “exhausted” lymphocyte profile. Overall, “pre-emptive” Ly-apheresis in DLBCL patients at high risk of relapse appears to be feasible and may allow the timely collection of “fit” lymphocytes for CAR-T cell manufacturing.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14215276