Enhanced detection and Characterization of M-proteins in multiple myeloma patients using An Agilent AssayMAP Bravo liquid handling system coupled to an LC-QTOF.

Background: Mass spectrometry methods are emerging as tools to detect M-proteins in the serum of multiple myeloma patients with increased sensitivity and specificity compared to traditional electrophoretic methods.

Methods: A liquid handling system, the Agilent AssayMAP Bravo, with liquid chromatography high-resolution quadrupole-time-of-flight (LC-QTOF) mass spectrometry to analyze intact light chains was compared to immunofixation electrophoresis (IFE) for M-protein analysis. 210 patient serum samples were analyzed in a split sample comparison (LC-QTOF vs.

BCMA-directed CAR T-cell Therapy in patients with multiple myeloma and CNS involvement.

We investigated BCMA-directed CART in patients with relapsed or refractory multiple myeloma (RRMM) and CNS involvement. Ten patients who received either ide-cel (n=6) or cilta-cel (n=4) were included in this analysis. Patients had brain/cranial nerve and/or spinal cord involvement/leptomeningeal disease evident on either MRI (100%) and/or CSF (40%).

Isatuximab plus pomalidomide and dexamethasone in frail individuals with relapsed/refractory multiple myeloma in Japan.

This post-marketing surveillance (PMS) assessed the safety and effectiveness of isatuximab plus pomalidomide and dexamethasone (Isa-Pd) for relapsed or refractory multiple myeloma (RRMM) in frail individuals during real-world use in Japan. Data from all individuals with RRMM treated with Isa-Pd in Japan between October 2020 and October 2021 were collected, with follow-up continued up to 12 months after starting Isa-Pd or until discontinuation. In the overall PMS population, 40 participants were classified as frail (33.

A successful haploidentical transplantation without conditioning regimen for a relapsed/refractory multiple myeloma patient after chimeric antigen receptor T-cell therapy.

Background Aims: With novel therapies improving prognosis, the complications of multiple myeloma after multi-line treatment, particularly myelosuppression, have become a crucial determinant of long-term outcomes. Non-myeloablative allogeneic hematopoietic stem cell transplantation is a feasible option, but the transplant-related mortality rate remains high. Our study presents a relapsed/refractory multiple myeloma patient with a 9-year disease history.

Practical insights into bispecific antibody therapy in multiple myeloma.

Introduction: The rise of recent novel therapies teclistamab, elranatamab, and talquetamab for the treatment of relapsed/refractory multiple myeloma (RRMM) is a rapidly evolving area with significant clinical implications that require exploration and evaluation.

Areas Covered: The current review highlights the clinical trial data, safety endpoints, and practical administration considerations for the bispecific therapies currently used in multiple myeloma. This article reviewed the efficacy and safety results between the three different bispecifics, and the differences in dosing and monitoring requirements.

The Influence of Nordic Walking Training on the Serum Levels of Sirtuins, FOXO3a, and Vitamin D Metabolites in Patients with Multiple Myeloma.

Background: Multiple myeloma, a malignancy of plasma cells, often involves the disruption of vitamin D metabolism. Vitamin D, acting through its receptor (VDR), affects transcription factors like FOXO and sirtuins, which regulate cellular processes. The impact of physical activity on these markers in multiple myeloma patients is unclear.

Prevalence and Significance of Incidental PET/CT Findings of Cancer Detected in Patients Evaluated for Their Primary Hematologic Malignancy: A Systematic Review.

In the evaluation of a patient's primary hematologic malignancy, positron emission tomography/computed tomography (PET/CT) imaging may incidentally detect a concerning abnormality suggestive of a second concurrent cancer. Despite accounting for nearly 10% of all cancers diagnosed in Canada, there has yet to be a systematic review focused on the prevalence and significance of these incidental PET/CT findings in the context of primary hematologic malignancies. As such, a systematic search strategy was employed on MEDLINE and Embase to document the prevalence and clinical significance of incidental PET/CT findings suggestive of a second concurrent cancer detected in patients evaluated for their primary hematologic malignancy.

High-Sensitivity Flow Cytometry for the Reliable Detection of Measurable Residual Disease in Hematological Malignancies in Clinical Laboratories.

Background: Monitoring of measurable residual disease (MRD) requires highly sensitive flow cytometry protocols to provide an accurate prediction of shorter progression-free survival. High assay sensitivity generally requires rapid processing to avoid cell loss from small bone marrow sample volumes, but this requirement conflicts with the need in most clinical cytometry laboratories for long processing and acquisition times, especially when multiple MRD studies coincide on the same day.

Methods: The proposed protocol was applied to 226 human bone marrow and 45 peripheral blood samples submitted for the study of MRD or the detection of rare cells.

Development of BCMA-Targeted Bispecific Natural Killer Cell Engagers for Multiple Myeloma Treatment.

Background: B-cell maturation antigen (BCMA)-targeted T cell-redirecting immunotherapies, including Chimeric Antigen Receptor (CAR) T-cell therapy and T-cell engagers have demonstrated remarkable success in treating relapsed/refractory (RR) multiple myeloma (MM), a malignancy of plasma cells. However, a significant challenge is the severe side effects associated with T-cell overactivation, leading to cytokine release syndrome and neurotoxicity in MM patients undergoing such therapies. Bispecific NK cell engagers (NKCEs) may offer a promising alternative by redirecting NK cell cytotoxic activity towards tumor cells without triggering cytokine release syndrome.

Real-World Effectiveness and Safety of Intravenous Daratumumab in Patients with Multiple Myeloma: A Multicenter, Observational Study from Korea.

Purpose: Daratumumab is a novel, first-in-class monoclonal antibody approved for use as monotherapy and in combination with other treatments for patients with multiple myeloma (MM). The aim of this observational study was to evaluate the effectiveness and safety of daratumumab in real-world clinical practice.

Materials And Methods: This observational multicenter study collected data from patients with MM treated in Korea between June 1, 2018, and February 28, 2022.

Mitochondria-associated programmed cell death: elucidating prognostic biomarkers, immune checkpoints, and therapeutic avenues in multiple myeloma.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the abnormal proliferation of plasma cells. Mitochondrial dysfunction and dysregulated programmed cell death (PCD) pathways have been implicated in MM pathogenesis. However, the precise roles of mitochondria-related genes (MRGs) and PCD-related genes (PCDRGs) in MM prognosis remain unclear.

Fibula flap reconstruction for maxillary stage 3 medication-related osteonecrosis of the jaw from recipient and donor site perspectives: a preliminary single-center study.

Background: While the surgical treatment of mandibular stage 3 medication-related osteonecrosis of the jaw (MRONJ) is well-documented, research on maxillary stage 3 MRONJ is limited. Antiresorptive medications can induce MRONJ and atypical femoral fracture (AFF), but their impact on the feasibility of using fibula flaps for reconstruction remains controversial. This study aimed to assess the surgical outcomes and functional recovery of fibula flap reconstruction for maxillary stage 3 MRONJ, considering both recipient and donor site outcomes.

CD38-specific immunoPET imaging for multiple myeloma diagnosis and therapeutic monitoring: preclinical and first-in-human studies.

Purpose: CD38 is a glycoprotein highly specific to multiple myeloma (MM). Therapeutics using antibodies targeting CD38 have shown promising efficacy. However, the efficient stratification of patients who may benefit from daratumumab (Dara) therapy and timely monitoring of therapeutic responses remain significant clinical challenges.

A Phase I Study of Romidepsin in Combination With Gemcitabine, Oxaliplatin, and Dexamethasone in Patients With Relapsed or Refractory Aggressive Lymphomas Enriched for T-Cell Lymphomas.

Introduction: Histone deacetylase inhibitors (HDACi) and combination chemotherapy are independently used to treat relapsed/refractory (R/R) lymphoma. In vitro studies suggest that the addition of HDACi to platinum-based chemotherapy is synergistic.

Patients And Methods: We conducted a phase I study of romidepsin, gemcitabine, oxaliplatin and dexamethasone (Romi-GemOxD) in R/R aggressive lymphomas with an expansion cohort in T-cell lymphomas.

Reduced elastin in multiple myeloma niche promotes cell proliferation.

Multiple myeloma (MM) malignant plasma cells accumulate in the bone marrow (BM) where their interactions with the microenvironment promote disease progression and drug resistance. Previously, we have shown that bone marrow mesenchymal stem cells (BM-MSCs) (MM and normal donors- ND) derived extracellular matrix (ECM) affected MM cell lines differentially with a pro-MM effect attributed to MM-MSCs' ECM. Here we studied the composition of BM-MSC's ECM (ND versus MM) with focus on elastin (ELN).

Is Tumor Growth Influenced by the Bone Remodeling Process?

In this study, we develop a comprehensive model to investigate the intricate relationship between the bone remodeling process, tumor growth, and bone diseases such as multiple myeloma. By analyzing different scenarios within the Basic Multicellular Unit, we uncover the dynamic interplay between remodeling and tumor progression. The model developed developed in the paper are based on the well accepted Komarova's and Ayati's models for the bone remodeling process, then these models were modified to include the effects of the tumor growth.

Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers.

Despite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refractory/relapsed (R/R) disease. Approaches to avoid tumor-intrinsic mechanisms of resistance such as immune pressure-mediated antigen downmodulation, are being broadly investigated. These strategies include BCMA/CD19 dual-targeting therapies, which may be of particular interest to patients with B cell lymphoma and multiple myeloma, where a specific double-positive immature subpopulation is commonly associated with poor prognosis and poor response to current treatments.

The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. The disease's complexity is underpinned by a variety of genetic and molecular abnormalities that drive its progression.

Methods: This review was conducted through a state-of-The-art literature search, primarily utilizing PubMed to gather peer-reviewed articles.

Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes.

Background: Adoptive therapy with umbilical cord blood (UCB) T-regulatory (Treg) cells can prevent graft vs. host disease (GVHD). We hypothesize that UCB Tregs can treat GVHD and synergize with ruxolitinib, Jak2 inhibitor, to improve outcomes.

FaMMily Affairs: Dissecting inherited contributions to multiple myeloma risk.

Etiological links to multiple myeloma (MM) remain poorly understood, though emerging evidence suggests a significant hereditary component. This review integrates current literature on inherited factors contributing to MM risk, synthesizing both epidemiologic and genomic data. We examine familial clustering patterns, assess genome-wide association studies (GWAS) that reveal common genetic variants linked to MM, and explore rare, high-penetrance variants in key susceptibility genes.

A lymph node lesion of hyper IL-6 syndrome mimicking plasmacytoma, IgG4-related disease, and Castleman disease.

A 72-year-old male patient presented fatigue, anemia, elevated total protein, IgG, IgG4, IL-6, and vascular endothelial growth factor (VEGF) levels. Initial diagnostics suspected multiple myeloma. A plane computed tomography (CT) scan showed pneumonia and the enlargement of generalized lymph nodes.

Monoclonal gammopathy of undetermined significance and the risk of thrombotic events: Results from iStopMM, a prospective population-based screening study.

Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma and related diseases but has also been associated with thrombosis. Prior studies have not been based on screened cohorts leading to bias. We assessed the risk of thrombosis in a cohort of 75 422 individuals over 40 years old who were screened for MGUS in Iceland.

Malaria parasite detection in Red Blood Cells with rouleaux formation morphology using YOLOv9.

Malaria is endemic in poverty-stricken regions of the world, and most diagnosis reveal comorbidity with other infectious diseases some of which manifest as a deformity of the structural arrangement of the Red Blood Cells (RBCs) during thin blood smear microscopy. This common occurring deformity is termed rouleaux formation, and it is the stacking together of RBCs like chains of coins. The presence of rouleaux formation indicates either a bacterial infection, connective tissue disease, chronic liver disease, multiple myeloma or diabetes among others, it is a highly common occurrence in malaria infected patients and according to the international council for standardization of hematology (ICSH), microscopists are mandated to report its presence.

The lifecycle and evolution of new regimens on the National Comprehensive Cancer Network Guidelines for newly diagnosed multiple myeloma.

Introduction: Prior studies have evaluated the level of evidence behind treatment options listed in the National Comprehensive Cancer Network (NCCN) guidelines, but no study has categorized the life cycle of regimens listed in the NCCN guidelines. We longitudinally assessed the life cycle for each regimen for newly diagnosed multiple myeloma. We track the date of first clinical data, the date of regimen addition to NCCN guidelines, the date phase 3 data (if performed) were reported, and the results of phase 3 trials.