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Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFRole of procalcitonin, C reactive protein and ferritin in cytokine release syndrome after CAR T-cell therapy in children and young adults.
Biomarkers
January 2025
Pediatric Intensive Care Unit, Hospital Sant Joan de Déu-University of Barcelona, Barcelona, Spain.
PurposeChimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity.
View Article and Find Full Text PDFArticle Synopsis
- FT596 is a novel cancer therapy using iPSC-derived CAR NK cells targeting CD19, designed to assess its safe dosage and effectiveness alone and with rituximab in patients with B-cell lymphoma.
- This phase 1 trial involved patients with relapsed or refractory B-cell lymphoma, administering FT596 after chemotherapy, with separate regimens for those receiving rituximab and those who did not.
- The study measured potential side effects while determining the optimal dose of FT596 and allowed modifications to the treatment based on patient tolerance and response.
Targeting Refractory Triple-Negative Breast Cancer with Sacituzumab Govitecan: A New Era in Precision Medicine.
Cells
December 2024
Department of Nursing, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia.
Advanced triple-negative breast cancer (TNBC) has poorer outcomes due to its aggressive behavior and restricted therapeutic options. While therapies like checkpoint inhibitors and PARP inhibitors offer some benefits, chemotherapy remains ineffective beyond the first line of treatment. Antibody-drug conjugates (ADCs) like sacituzumab govitecan-hziy (SG) represent a significant advancement.
View Article and Find Full Text PDFPatient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.
Lancet Haematol
January 2025
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.
Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).
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