Burkitt lymphoma (BL) is an aggressive B-cell lymphoma associated with poor outcomes in patients with relapsed/refractory disease. This multicenter, retrospective study evaluated real-world CD19 CAR T-cell therapy outcomes in patients with relapsed/refractory BL using data abstracted from the medical records. In total, 31 patients received CAR T-cells after a median of 3 prior therapies (range 1-6). Patients received axi-cel (n = 19), liso-cel (n = 4), tisa-cel (n = 4) or other agents (n = 4). Grade 1-2 CRS occurred in 83.9% of patients (grade ≥3 6.5%), and grade 1-2 ICANS occurred in 29% of patients (grade ≥3 19.4%). Twenty-eight-day mortality was 16.1%, including one patient who died from grade 5 ICANS. The overall response rate at 1 month was 58.0% with a complete response (CR) rate of 41.9%, however the 6-month CR rate was only 25.8%. Median progression-free survival was 2.3 months (95% CI 1.0 - 9.0), and median overall survival was 6.0 months (95% CI 1.9 - 11.5). Three patients (9.7%) received consolidative allogeneic stem cell transplants, but all subsequently relapsed. In conclusion, CD19 CAR T-cell therapy infrequently delivers long term disease control in BL. Further investigation is needed to determine the most effective alternative management of these patients.
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http://dx.doi.org/10.1182/blood.2024026831 | DOI Listing |
J Immunol
March 2025
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, United States.
Natural killer (NK) cells express activating receptors that signal through ITAM (immunoreceptor tyrosine-based activation motif)-bearing adapter proteins. The phosphorylation of each ITAM creates binding sites for SYK and ZAP70 protein tyrosine kinases to propagate downstream signaling including the induction of Ca2+ influx. While all immature and mature human NK cells coexpress SYK and ZAP70, clonally driven memory or adaptive NK cells can methylate SYK genes, and signaling is mediated exclusively using ZAP70.
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March 2025
Department of Hematology and Medical Oncology, Advocate Lutheran General Hospital, Park Ridge, IL 60068, USA.
The landscape of adult acute lymphoblastic leukemia (ALL) is dramatically changing. With very promising results seen with novel immunotherapeutics in the setting of relapsed and refractory disease, the prospect of using these agents in first-line therapy has prompted the development of multiple clinical trials addressing this question. This review seeks to outline and expand the current standard of care, as well as new advances, in the treatment of adult patients with ALL and address future areas of research.
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February 2025
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China.
Chimeric antigen receptor (CAR) gene-modified T-cell therapy has achieved significant success in the treatment of hematological malignancies. However, this therapy has not yet made breakthroughs in the treatment of solid tumors and still faces issues of resistance and relapse in hematological cancers. A major reason for these problems is the antigenic heterogeneity of tumor tissues.
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Vasculitis Expertise Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
In this plenary session of the Vasculitis Workshop 2024, pioneering translational research on autoimmune vasculitis, particularly ANCA-associated vasculitis (AAV), was presented, highlighting advancements in our understanding of disease mechanisms and promising therapeutic prospects. Advances in elucidating molecular pathways, such as IL-17 and IFN-I, pave the way for specific treatments. Preclinical studies have revealed the gut microbiome's role in the pathogenesis of MPO-AAV and demonstrate the therapeutic potential of dietary interventions.
View Article and Find Full Text PDFRheumatology (Oxford)
March 2025
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
ANCA vasculitis is a systemic autoimmune small-vessel vasculitis characterized by autoantibodies targeting either MPO or PR3. While patients with ANCA vasculitis are successfully treated with broad-spectrum immunosuppression, these treatments often leave patients vulnerable to infections. Research in the field has made positive gains in regards to understanding autoantigen specificity and immune cell subset involvement in disease pathogenesis, relapse and remission.
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