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Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care.
View Article and Find Full Text PDFA Bayesian Joint Model of Multiple Nonlinear Longitudinal and Competing Risks Outcomes for Dynamic Prediction in Multiple Myeloma: Joint Estimation and Corrected Two-Stage Approaches.
Stat Med
February 2025
Hoffmann-La Roche Ltd, Basel, Switzerland.
Predicting cancer-associated clinical events is challenging in oncology. In Multiple Myeloma (MM), a cancer of plasma cells, disease progression is determined by changes in biomarkers, such as serum concentration of the paraprotein secreted by plasma cells (M-protein). Therefore, the time-dependent behavior of M-protein and the transition across lines of therapy (LoT), which may be a consequence of disease progression, should be accounted for in statistical models to predict relevant clinical outcomes.
View Article and Find Full Text PDFElevated LIF and JAK-STAT activation drive severe COVID-19 in myeloma patients receiving the BCMA-CD3 bispecific antibody Elranatamab.
J Transl Med
January 2025
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, China.
Background: Immunotherapy is a significant risk factor for severe COVID-19 in multiple myeloma (MM) patients. Understanding how immunotherapies lead to severe COVID-19 is crucial for improving patient outcomes.
Methods: Human protein microarrays were used to examine the expression of 440 protein molecules in MM patients treated with bispecific T-cell engagers (BiTe) (n = 9), anti-CD38 monoclonal antibodies (mAbs) (n = 10), and proteasome inhibitor (PI)-based regimens (n = 10).
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 PDFMonitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma.
Pharmaceutics
January 2025
Laboratory Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Multiple Myeloma (MM) is a hematologic malignancy caused by clonally expanded plasma cells that produce a monoclonal immunoglobulin (M-protein), a personalized biomarker. Recently, we developed an ultra-sensitive mass spectrometry method to quantify minimal residual disease (MS-MRD) by targeting unique M-protein peptides. Therapeutic antibodies (t-Abs), key in MM treatment, often lead to deep and long-lasting responses.
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