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Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial.

BACKGROUND: Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. METHODS: This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who we…

Hypoxia promotes BCMA loss and a suppressive secretome thereby hindering CAR T cell therapy in multiple myeloma.

INTRODUCTION: Multiple myeloma (MM) develops in the hypoxic bone marrow (BM) microenvironment, which alters tumor behavior and immune responses. While hypoxia is known to directly suppress immune function, its effect on immunotherapy-relevant antigen expression and the MM secretome remains underexplored. Here, we investigated how hypoxia affects BCMA expression and BCMA-targeted CAR T cell responses. METHODS: MM cells were cultured under normoxia (21% O₂) or hypoxia (1% O₂). BCMA surface and total expression were analyzed. Anti-BCMA CAR T cells were co-cultured with normoxic or hypoxic MM cel…

Precision radiolabeled B-cell maturation nanobody for targeted PET imaging and radioligand therapy of disseminated multiple myeloma.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with limited disease-specific imaging options. Current diagnostic methods often fail to detect early disease states and minimal residual disease, highlighting the need for more precise molecular imaging and targeted therapeutic approaches. We developed a radiolabeled nanobody targeting B-cell maturation antigen (BCMA) to enable both high-contrast molecular imaging and targeted radioligand therapy in human MM models. Methods: A high-affinity anti-BCMA nanobody was labeled with [18F]FPy-pyridine prosthetic group for PET ima…

Automated abstraction of clinical parameters of multiple myeloma from real-world clinical notes using large language models.

BACKGROUND: Real-world evidence (RWE) is increasingly recognized as a valuable type of oncology research but extracting fit-for-purpose real-world data (RWD) from electronic health records (EHRs) remains challenging. Manual abstraction from free-text clinical documents, although the gold standard for information extraction, is resource-intensive. RWD generation using natural language processing (NLP) has been limited by performance ceilings and annotation requirements, which recent LLMs improve on. Multiple myeloma (MM) is the second most common hematological malignancy, with many opportunitie…

CD138-targeted bispecific protein engager-armed T cells exhibit potent and selective cytotoxicity against multiple myeloma cells.

Multiple myeloma (MM) is a hematologic malignancy that remains incurable, with most patients eventually relapsing or developing resistance to available therapies. Bispecific T cell engagers (BiTEs) have shown promise by redirecting T cells to target and kill tumor cells; however, their clinical application is hindered by a short in vivo half-life, the need for high dosing, and treatment-related toxicities. To address these limitations, bispecific protein engager-armed T cells (BATs) have been developed as a novel cell-based immunotherapy platform that enhances antigen specificity and in vivo p…

The risk of multiple myeloma associated with daily low-dose exposure to ionising radiation from radon decay.

BACKGROUND: Ionising radiation is suspected to increase the risk of multiple myeloma (MM) but has mostly been investigated at occasional high doses rather than exposure to continuous low doses at home. METHODS: In this ecological study, we investigated the association between MM and radon based on the geographical distribution of MM patients in Denmark diagnosed from 2005 to 2020 and a national radon survey carried out by the Danish authorities based on 3019 random selected single-family houses. A linear association was assessed between age- and sex-standardised incidence rate (SIR) of MM and…

Lesion-level dual-tracer PET biomarkers predict prognosis in multiple myeloma treated with CXCR4-directed radiopharmaceutical therapy.

BACKGROUND: C-X-C motif chemokine receptor 4 (CXCR4)-directed radiopharmaceutical therapy (RPT) represents a promising option for hematologic malignancies. Nevertheless, responses in relapsed and refractory (r/r) multiple myeloma (MM) are heterogenous, emphasizing the need for optimized patient selection before RPT. Current approaches mostly rely on qualitative assessments, confirming relevant CXCR4-expression by CXCR4-directed PET in vital myeloma burden, the latter usually being determined by additional [18F]FDG-PET. PURPOSE: To evaluate whether quantitative imaging biomarkers derived from …

Single-cell profiling reveals MIF-mediated immune evasion and CD8 + T cell exhaustion in relapsed multiple myeloma.

Multiple myeloma (MM) is a heterogeneous hematologic cancer marked by clonal plasma cell expansion in the bone marrow. Although treatments have improved, relapse remains common due to clonal evolution, tumor microenvironment changes, ultimately leading to drug resistance. This study utilized single-cell RNA sequencing data analysis to explore immune microenvironment dynamics during MM progression and relapse, aiming to uncover key pathways and cellular interactions correlated with disease relapse. ScRNA-seq data from 20 MM patients (10 primary, 2 remission, 8 relapsed) from the GEO dataset GSE…

Imeglimin Exerts Anti-Tumor Activity in Multiple Myeloma Through Affecting Energy Metabolism and Downregulating IL-16 Expression.

BACKGROUND: Imeglimin (IME) is a novel oral anti-diabetic agent with a similar chemical structure to metformin, which has shown broad-spectrum anti-tumor activity. However, the activity of imeglimin on tumor cells remains unclear. This study investigated the effects of IME on multiple myeloma (MM) cells and explored the underlying mechanisms. METHODS: The effects of IME on MM cell proliferation were evaluated in vitro using MM cell lines and in MM cell-derived xenograft (CDX) models. Seahorse metabolic analyses and RNA-Seq were performed in IME-treated and control MM cell lines. Single-cell t…

Модель индекса питания для прогнозирования резистентности и прогнозирования в множественных миеломах после аутологической трансплантации стволовых клеток.

Множественная миелома - это one Наиболее распространенные гематологические заболевания во всем мире создают серьезную угрозу для жизни и здоровья населения. В последние годы все больше и больше исследователей включили прогнозный индекс питания (ПНИ) в прогнозные исследования опухолей и провели оценку состояния питания и прогнозировали долгосрочный прогноз пациентов в рамках ПНИ. МЕТОДЫ: Медицинские записи 245 Пациенты с множественными миеломами, получившие автологическую трансплантацию стволовых клеток в нашей больнице с февраля 2011 по июль 2018 был ретроспективно проанализирован. Оптимальное…

Plant cytokinin ortho-topolin riboside suppresses the proliferation of multiple myeloma cells by promoting β-catenin degradation.

The shift to the circular economy has led to the use of plant-based functional ingredients in sustainable food packaging. Renewable, biodegradable, and non-toxic polysaccharides, proteins, lipids, and biopolymers include alginate, chitosan, starch, cellulose, pectin, soy protein, and polylactic acid (PLA). Hydrophobization gives antibacterial, antioxidant, UV-protective, and pH-responsive properties. Lignin is an antioxidant, antibacterial, and UV-blocking filler. A blend of carboxymethyl chitosan and soy protein isolate has almost 100% antimicrobial effects against Escherichia coli (E. coli)

Central venous catheter rupture following undiluted etoposide administration in a patient with multiple myeloma: A case report.

Central venous catheter (CVC) rupture is an uncommon but clinically significant complication. We report a case involving a 59-year-old woman with multiple myeloma who experienced CVC rupture following prolonged infusion of undiluted etoposide (VP‑16). The patient received continuous VP‑16 infusion through a polyurethane double-lumen catheter and subsequently developed puncture-site pain, local oozing, and catheter malfunction. Radiography did not initially demonstrate catheter displacement or breakage. After multidisciplinary evaluation, the catheter was removed, revealing a longitudinal intra…

Identification of two novel TP53 mutations in secondary acute myeloid leukemia following multiple myeloma: a case report.

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… Integrating p53-associated genes and infiltrating immune cell characterization as a prognostic biomarker in multiple myeloma. Heliyon 2024;10(8):e30123. [2] Huang J, Chan SC, Lok V, et al. … Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol 2015;33(26):2863–2869. [8] Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20(9):1467–1473. …

CD38-Targeted Small-Molecule PET Radiotracer for Noninvasive Tumor Evaluation and Preliminary Therapy Monitoring in Multiple Myeloma.

CD38 is an established biomarker for the diagnosis and treatment of various malignancies, including multiple myeloma. Accurate assessment of CD38 expression holds significant clinical value for optimizing CD38-targeted therapies. This study developed a series of small-molecule radiotracers for in vivo assessment of CD38 expression and monitoring of therapeutic response. All 68Ga-labeled radiotracers exhibited high radiochemical purity and stability both in vitro and in vivo. PET/CT imaging showed that 68Ga-NOTA-MK0159 uptake in multiple myeloma models correlated positively with CD38 expression…

Outpatient Delivery of Step-Up Doses to Rapidly Initiate Monthly Doses of Bispecific Antibodies in Multiple Myeloma.

AIMS: New therapies are improving outcomes even in advanced stages of multiple myeloma. OBJECTIVES: To describe the experience of bispecific antibodies (BsAbs) in Mexico. RESULTS: The study included 41 patients with triple-class refractory (88%) and penta-drug refractory (61%) myeloma. The median number of prior treatment lines was 3, and the median time to response was 2 months. Step-up dosages were administered on an outpatient basis in 34 patients (83%). BsAbs were administered every 2 weeks to 19 patients (46%) and monthly to 17 patients (41.5%). Thirteen of these (31.5%) switched to mon…

Disease Stage-Dependent Clinical Impact of CTLA4 Polymorphism in Multiple Myeloma Treated with Autologous Stem Cell Transplantation.

BACKGROUND: Clinical outcomes for multiple myeloma are highly variable. Inherited genetic variants of immune regulatory genes can modulate disease susceptibility and clinical outcomes. The germline variant CTLA4 rs231775 polymorphism may alter T-cell function and affect clinical outcomes. METHODS: We conducted a retrospective single-center study including 156 consecutive myeloma patients who underwent first-line ASCT. The patients were stratified according to the CTLA4 rs231775 genotype and disease stage (ISS I-III). RESULTS: The CTLA4 rs231775 AA genotype was associated with inferior PFS in…

[Delayed response with peripheral blood CD8+ T cell expansion during elranatamab therapy in relapsed/refractory multiple myeloma].

We report the case of an 81-year-old woman with relapsed/triple-class refractory multiple myeloma (IgA-λ type) complicated by acute kidney injury, who received elranatamab as seventh-line therapy. Serum free light chain (sFLC) levels decreased and renal function improved shortly after treatment initiation, and IgA declined after 4.9 months, ultimately resulting in a deep response. Notably, marked peripheral CD8+ T cell expansion was observed at the onset of response, and counts remained elevated during sustained remission. This case suggests that early sFLC reduction is a useful indicator for …

Meaningful change in patient-reported outcomes after CAR-T for multiple myeloma: differences by race and ethnicity.

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… TO THE EDITOR: Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized treatment for relapsed/refractory multiple myeloma (RRMM). … with idecabtagene vicleucel in relapsed and refractory multiple myeloma Blood Adv 6 4 2022 1309 1318 34933328 10.1182/bloodadvances.2021005913 PMC8864645 6 Martin T Lin Y Agha M Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE …