Bridging therapy before CD19-directed chimeric antigen receptor (CAR) T-cell infusion is frequently applied in patients with relapsed or refractory Large B-cell lymphoma (r/r LBCL). This study aimed to assess the influence of quantified MATV and MATV-dynamics, between pre-apheresis (baseline) and pre-lymphodepleting chemotherapy (pre-LD) MATV, on CAR T-cell outcomes and toxicities in patients with r/r LBCL. MATVs were calculated semi-automatically at baseline (n = 74) and pre-LD (n = 68) in patients with r/r LBCL who received axicabtagene ciloleucel. At baseline, patients with a low MATV (< 190 cc) had a better time to progression (TTP) and overall survival (OS) compared to high MATV patients (p < 0.001). High MATV patients who remained stable or reduced upon bridging therapy showed a significant improvement in TTP (p = 0.041) and OS (p = 0.015), compared to patients with a high pre-LD MATV (> 480 cc). Furthermore, high MATV baseline was associated with severe cytokine release syndrome (CRS, p = 0.001). In conclusion, patients with low baseline MATV had the best TTP/OS and effective reduction or controlling MATV during bridging improved survival outcomes in patients with a high baseline MATV, providing rationale for the use of more aggressive bridging regimens.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917787PMC
http://dx.doi.org/10.1038/s41408-024-01022-wDOI Listing

Publication Analysis

Top Keywords

car t-cell
12
r/r lbcl
12
t-cell infusion
8
large b-cell
8
b-cell lymphoma
8
patients r/r
8
patients
5
reducing controlling
4
controlling metabolic
4
metabolic active
4

Similar Publications

Chimeric antigen receptor (CAR) T cell therapy for solid tumors faces significant challenges, including inadequate infiltration, limited proliferation, diminished effector function of CAR T cells, and an immunosuppressive tumor microenvironment (TME). In this study, we utilized The Cancer Genome Atlas database to identify key chemokines (CCL4, CCL5, and CCR5) associated with T cell infiltration across various solid tumor types. The CCL4/CCL5-CCR5 axis emerged as significantly correlated with the presence of T cells within tumors, and enhancing the expression of CCR5 in CAR T cells bolstered their migratory capacity.

View Article and Find Full Text PDF

[Anti-tumor therapy strategy of CAR-T cells based on stem cell memory and central memory cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi

December 2024

Center for Cancer Immunotherapy, Institute of Biomedicine and Biotechnology, Chinese Academy of Sciences, Shenzhen 518055; University of Chinese Academy of Sciences, Beijing 101408; Laboratory of Human Environmental Epigenomes, Department of Biopharmaceutical Sciences, School of Pharmaceutical Science, Shenzhen University of Advanced Technology, Shenzhen 518107, China.*Corresponding author, E-mail:

Cancer immunotherapy including immune checkpoint inhibitors and adoptive cell therapy has gained revolutionary success in the treatment of hematologic tumors; however, it only gains limited success in solid tumors. For example, chimeric antigen receptor T (CAR-T) cell therapy has shown significant effects and potential for curing patients with B-cell malignancies. In contrast, it remains a challenge for CAR-T cell therapy to gain similar success in solid tumors.

View Article and Find Full Text PDF

CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives.

Front Immunol

January 2025

Innovation & Research Department, OriCell Therapeutics Co. Ltd., Shanghai, China.

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) are debilitating autoimmune disorders characterized by pathological autoantibodies production and immune dysfunction, causing chronic inflammation and multi-organ damage. Despite current treatments with antimalarial drugs, glucocorticoids, immunosuppressants, and monoclonal antibodies, a definitive cure remains elusive, highlighting an urgent need for novel therapeutic strategies. Recent studies indicate that chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in treating B-cell malignancies and may offer a significant breakthrough for non-malignant conditions like SLE.

View Article and Find Full Text PDF

Gamma delta T cells in cancer therapy: from tumor recognition to novel treatments.

Front Med (Lausanne)

December 2024

The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China.

Traditional immunotherapies mainly focus on αβ T cell-based strategies, which depend on MHC-mediated antigen recognition. However, this approach poses significant challenges in treating recurrent tumors, as immune escape mechanisms are widespread. γδ T cells, with their ability for MHC-independent antigen presentation, offer a promising alternative that could potentially overcome limitations observed in traditional immunotherapies.

View Article and Find Full Text PDF

Background: Due to the lack of effective treatment options, the prognosis of patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains poor. Although chimeric antigen receptor (CAR)-T-cell therapy has shown promising effects in acute lymphoblastic leukemia (ALL) and lymphoma, its application in R/R AML is limited by "off-target" effects, which lead to severe bone marrow suppression and limit its clinical application. CAR-natural killer (NK) cells not only exhibit antitumor effects but also demonstrate increased safety and universality.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!