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CD19-directed chimeric antigen receptor T-cell (CAR T) therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have transformed the treatment landscape for B-cell non-Hodgkin lymphoma, showcasing significant efficacy but also highlighting toxicity risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The US Food and Drug Administration has mandated patients remain close to the treatment center for 4 weeks as part of a Risk Evaluation and Mitigation Strategy to monitor and manage these toxicities, which, although cautious, may add to cost of care, be burdensome for patients and their families, and present challenges related to patient access and socioeconomic disparities. This retrospective study across 9 centers involving 475 patients infused with axi-cel, tisa-cel, and liso-cel from 2018 to 2023 aimed to assess CRS and ICANS onset and duration, as well as causes of nonrelapse mortality (NRM) in real-world CAR T recipients. Although differences were noted in the incidence and duration of CRS and ICANS between CAR T products, new-onset CRS and ICANS are exceedingly rare after 2 weeks after infusion (0% and 0.7% of patients, respectively). No new cases of CRS occurred after 2 weeks and a single case of new-onset ICANS occurred in the third week after infusion. NRM is driven by ICANS in the early follow-up period (1.1% until day 28) and then by infection through 3 months after infusion (1.2%). This study provides valuable insights into optimizing CAR T therapy monitoring, and our findings may provide a framework to reduce physical and financial constraints for patients.
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http://dx.doi.org/10.1182/bloodadvances.2023012549 | DOI Listing |
Clin Cancer Res
September 2025
Amgen (United States), Thousand Oaks, CA, United States.
Purpose: Tarlatamab is a first-in-class, half-life extended bispecific T-cell engager (BiTE®) immunotherapy targeting delta-like ligand 3 (DLL3) currently approved for the treatment of adult patients with small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Here we report tarlatamab exposure-response relationships to inform dose selection in patients with SCLC.
Experimental Design: Pharmacokinetic data were correlated with therapeutic effect [exposure-response (ER) analyses] for efficacy and safety measures using pooled data from DeLLphi-300 and DeLLphi-301 studies.
Z Rheumatol
September 2025
Medizinische Klinik 3 - Rheumatologie und Immunologie, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Deutschland.
Background: Chimeric antigen receptor T-cells (CAR T-cells) are an effective therapeutic approach in the treatment of B-cell driven malignancies. In addition to malignant B-cells, autoreactive B-cells are important targets for CD19 CAR T-cells, as they are a source of autoantibody production and support both the onset and progression of systemic lupus erythematosus (SLE). We and others have shown that their use in severe and therapy-refractory cases of SLE is effective and, moreover, safe.
View Article and Find Full Text PDFRinsho Ketsueki
September 2025
Department of Hematology, Japanese Red Cross Medical Center.
A 58-year-old woman received chimeric antigen receptor T-cell (CAR-T) therapy for triple-class refractory multiple myeloma. Following CAR-T infusion, she developed severe cytokine release syndrome (CRS) and was promptly admitted to the intensive care unit (ICU). Subsequently, she developed immune effector cell-associated neurotoxicity syndrome (ICANS), and then progressed to cardiac arrest.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
September 2025
Department of Hematology-Oncology, Hotel-Dieu de France, Beirut, Lebanon. Electronic address:
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma, with R-CHOP as the standard first-line treatment. However, many patients experience relapse or refractory disease, prompting the need for new therapeutic approaches. Recent advances, including chimeric antigen receptor (CAR) T-cell therapies, antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), immunomodulators, and Exportin-1 (XPO-1) inhibitors have transformed treatment strategies.
View Article and Find Full Text PDFBlood Adv
September 2025
UCSF, San Francisco, California, United States.
Accumulating real-world (RW) evidence of axi-cel has demonstrated comparable performance to the pivotal trials. However, nearly 57% of patients eventually experience relapse, with most requiring additional therapies. Being able to identify patients with risk of early relapse enables clinicians to consider additional interventions to further extend survival outcomes.
View Article and Find Full Text PDF