80,949 results match your criteria: "Myeloma"

High-risk cytogenetic abnormalities in multiple myeloma: PETHEMA-GEM experience.

Hemasphere

December 2024

Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC) CIBERONC Salamanca Spain.

This study examines the impact of cytogenetic abnormalities and their co-segregation on the prognosis of newly diagnosed multiple myeloma patients. The analysis included 1304 patients from four different GEM-PETHEMA clinical trials. Genetic alterations, such as t(4;14), t(14;16), del(17p), +1q, and del(1p), were investigated using FISH on CD38 purified plasma cells.

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Despite recent advancements in treatments, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains mostly incurable with patients frequently experiencing disease relapses due to therapy resistance. Hence there is an urgent need for innovative treatments for patients with relapsed and/or refractory MM (RRMM). This review examines Belantamab mafodotin, the first antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), which has shown efficacy in pre-clinical and clinical settings for RRMM.

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The treatment of multiple myeloma (MM) has significantly advanced; however, the underlying genetic mechanisms remain elusive. Clonal events and genetic alterations are recognized as pivotal in the pathogenesis of MM. It is now understood that a multitude of gene mutations, including those affecting RAS, , , and 1q21 amplification, are prevalent in this disease.

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Minimal residual disease in multiple myeloma.

Presse Med

December 2024

Sorbonne Université, Centre de Recherche Saint-Antoine INSERM UMRs938, Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France. Electronic address:

Minimal Residual Disease (MRD) in multiple myeloma has emerged as a significant prognostic factor, guiding treatment strategies and enhancing patient outcomes. Despite advancements in therapies such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, CAR-T cell therapy, and bispecific antibodies, complete eradication of malignant plasma cells remains challenging. MRD refers to a small number of residual cancer cells that persist after treatment and require sensitive methods like next-generation flow cytometry (NGF) and next-generation sequencing (NGS) for detection.

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Kidney disease in multiple myeloma.

Presse Med

December 2024

Division of Pathology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Canada.

Article Synopsis
  • * Quick diagnosis and treatment of kidney problems in these patients are crucial, with therapies focusing on hydration, correcting contributing factors, and administering effective anti-myeloma drugs while considering the patient's kidney function and overall health.
  • * Advanced treatments like plasma exchange may improve kidney recovery in severe cases, and newer combinations of medications show promise, with the possibility of kidney transplantation for some patients in the future.
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Although the prognosis of patients with multiple myeloma (MM) has been significantly improved by the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, MM is still considered an incurable disease in the vast majority of the patients. In recent years, T-cell based immunotherapy represents a novel treatment strategy for relapsed/refractory (RR) MM. So far, chimeric antigen receptor (CAR) modified T-cells and bispecific T-cell engaging antibodies (bsAb) have shown promising anti-MM efficacy and manageable safety profile within clinical trials, and B-cell maturation antigen (BCMA) is the most commonly used immune target for T-cell based immunotherapies in MM.

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Imaging in multiple myeloma.

Presse Med

December 2024

Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America. Electronic address:

Multiple myeloma (MM) is the second most common adult hematologic malignancy, characterized by clonal proliferation of malignant plasma cells mostly in the bone marrow. The presence of destructive changes of the mineralized bone is a hallmark feature of the condition and a sign of end-organ damage. Due to this, imaging plays an integral role in the diagnosis, prognostication, and treatment monitoring of patients undergoing therapy for MM as well as surveillance of patients with early-stage disease.

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Evolving strategies in the management of transplant-eligible patients with newly diagnosed multiple myeloma.

Presse Med

December 2024

Service d'Hematologie, CHU de Toulouse - IUCT Oncopole, Université UPS Toulouse 3, Toulouse, France. Electronic address:

Multiple myeloma treatment has evolved significantly with the introduction of triplet and quadruplet regimens, notably incorporating anti-CD38 antibodies. While autologous stem cell transplantation remains a cornerstone of therapy, its role in the context of increasingly effective upfront treatments is debated. Current guidelines still recommend transplant for all eligible patients, especially those with high-risk features at diagnosis, despite concerns regarding the lack of overall survival benefits and the potential long-term toxicities associated with high-dose melphalan.

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Background And Aims: Serum protein electrophoresis interpretation requires a substantial amount of manual work. In 2020, Chabrun et al. created a machine learning method called SPECTR for the task.

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CAR-iNKT cell therapy: mechanisms, advantages, and challenges.

Curr Res Transl Med

December 2024

Beijing Rongai Biotechnology Co., Ltd, 1st Floor, Building 29, No. 5 Kechuang East 2nd Street, Tongzhou District, Beijing 101100, China. Electronic address:

Article Synopsis
  • CAR T-cell therapy has shown significant promise in treating blood cancers like B-ALL and multiple myeloma, leading to new approvals of CAR-T products that benefit many patients.
  • However, its use in solid tumors is limited due to challenges like tumor microenvironments, variable antigen expression, and side effects.
  • Invariant natural killer T (iNKT) cells, with their unique properties, are being investigated as a complement to CAR-T therapy, and researchers are exploring CAR technology to enhance iNKT cells’ effectiveness in targeting solid tumors.
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Elevated levels of the nicotinamide adenine dinucleotide (NAD+)-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in Multiple Myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials due to the existence of alternative NAD+ production routes utilizing NAD+ precursors other than nicotinamide.

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Sulforaphane inhibits multiple myeloma cell-induced osteoclast differentiation and macrophage proliferation by elevating ferroportin1.

Cancer Chemother Pharmacol

December 2024

Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Purpose: Osteolysis is a common complication in patients with multiple myeloma (MM). Our previous studies have demonstrated that MM cells can promote osteoclast differentiation of macrophages. In this study, we explored the effect of sulforaphane (SFN), a natural NRF2 activator found in broccoli, on MM cell-induced osteoclast differentiation.

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Introduction: Teclistamab, the first approved B-cell maturation antigen-directed bispecific antibody for treatment of triple-class exposed relapsed/refractory multiple myeloma, demonstrated deep, durable responses with a manageable safety profile in the pivotal MajesTEC-1 cohort (NCT03145181/NCT04557098). Efficacy, safety, and pharmacokinetics from the MajesTEC-1 China cohort are reported.

Methods: Patients received teclistamab 1.

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Background: T-cell-redirecting therapies, such as bispecific antibodies and chimeric antigen receptor T-cells, exploit the cytotoxic capabilities of the immune system to destroy cells expressing specific surface antigens, including malignant cells. These therapies have demonstrated unprecedented rates, depth, and duration of responses in relapsed and refractory multiple myeloma. However, there are significant challenges in implementing these therapies into practice, which require multidisciplinary and multicenter coordination and significant healthcare resources to effectively manage these patients.

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Article Synopsis
  • - The study investigates how SARS-CoV-2 monoclonal antibody (mAB) therapy affects the immune response in five cancer patients infected with the virus, comparing them to non-mAB-treated controls.
  • - Blood samples were analyzed for various immune responses, revealing that all patients produced antibodies and T-cell responses similar to those of controls, despite some having B-cell deficiencies.
  • - The findings indicate that mAB therapy results in a robust immune response against SARS-CoV-2 in cancer patients, showing the potential for effective protective immunity even with underlying malignancies.
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Selective PET imaging of CXCR4 using the AlF-labeled antagonist LY2510924.

Eur J Nucl Med Mol Imaging

December 2024

Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

Background: [Ga]PentixaFor detects C-X-C chemokine receptor type 4 (CXCR4) overexpression in various malignancies, such as multiple myeloma and non-Hodgkin lymphomas, as well as in endocrine and inflammatory disorders. This study aimed to develop an AlF-labeled radiotracer derived from LY2510924 for CXCR4-targeted imaging, leveraging the physical and logistical advantages of fluorine-18.

Methods: We designed a CXCR4-specific radioprobe, [F]AlF-NOTA-SC, based on LY2510924 by incorporating a triglutamate linker and NOTA chelator to enable AlF-labeling.

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The global multiple myeloma incidence and mortality burden in 2022 and predictions for 2045.

J Natl Cancer Inst

December 2024

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

Background: Multiple myeloma (MM) is an important haematological malignancy in older adults, with a relatively poor prognosis. We aimed to present the current global patterns of incidence and mortality from MM, and predict new cases and deaths by 2045.

Methods: Estimated numbers of MM cases and deaths and age-standardized (World) incidence and mortality rates per 100,000 people were obtained from the GLOBOCAN 2022 database covering 185 countries.

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Conventional approaches to predict protein involvement in cancer often rely on defining either aberrant mutations at the single-gene level or correlating/anti-correlating transcript levels with patient survival. These approaches are typically conducted independently and focus on one protein at a time, overlooking nucleotide substitutions outside of coding regions or mutational co-occurrences in genes within the same interaction network. Here, we present CancerHubs, a method that integrates unbiased mutational data, clinical outcome predictions and interactomics to define novel cancer-related protein hubs.

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Background: Secondary malignancies are potential complications after high-dose therapy and autologous stem cell transplantation (ASCT). Information on the detailed course of such events is scarce, yet may be essential to minimize the impact of these sequelae.

Patients And Methods: We regularly monitored 877 patients for up to 31 years after ASCT in our outpatient department.

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Therapy adherence can significantly influence the outcome of cancer patients. The prospective, non-interventional CARO study (NCT02970747) investigated adherence, effectiveness, and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in the German real-world setting. In total, 359 patients were included at 69 sites.

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Pseudokinase TRIB3 stabilizes SSRP1 via USP10-mediated deubiquitination to promote multiple myeloma progression.

Oncogene

December 2024

Department of Hematology, the Second Xiangya Hospital; School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, Hunan, 410011, China.

Multiple myeloma (MM), the world's second most common hematologic malignancy, poses considerable clinical challenges due to its aggressive progression and resistance to therapy. Addressing these challenges requires a detailed understanding of the mechanisms driving MM initiation, progression, and therapeutic resistance. This study identifies the pseudokinase tribble homolog 3 (TRIB3) as a high-risk factor that promotes MM malignancy in vitro and in vivo.

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Bone marrow stromal cells protect myeloma cells from ferroptosis through GPX4 deSUMOylation.

Cancer Lett

December 2024

Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China. Electronic address:

Bone marrow stromal cells (BMSCs) are vital for preventing chemotherapy induced apoptosis of multiple myeloma (MM), but roles and machinery in other forms of cell death have not been well elucidated. Here, using an in vitro BMSC-MM interacting model, we observed BMSCs protected MM cells from labile iron pool (LIP) and reactive oxygen species (ROS) triggered ferroptosis by elevating glutathione peroxidase 4 (GPX4). Mechanistically, direct interaction with BMSCs upregulated the expression of SUMO-specific protease 3 (SENP3) in MM cells through CD40/CD40L signaling pathway, and SENP3 de-conjugated SUMO2 at lysine 75 residue to stabilize GPX4 protein, thereby consuming ROS to obviate ferroptosis in MM cells from the Vk∗MYC mouse model, as well as in CD138B220 cells separated from the Cd40l;Prx1 mice (CD40-CKO) and Sumo2 knock out (SUMO2-KO) mice.

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