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Myeloma bone disease: Pathophysiology and management.

Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases t…

Highlighting recent achievements to advance more effective cancer immunotherapy.

From 17 to 19th October 2024, the XXI Italian Network for Bio-Immunotherapy of Tumors Meeting (NIBIT) took place in Palermo, in the marvelous historical location of Teatro Politeama, under the auspices of the Italian Association of Medical Oncology (AIOM), Italian Association of Cancer Research (AIRC), Fondazione Pezcoller, Italian Alliance against Cancer (ACC), Italian Lymphoma Foundation (FIL), Grazia Focacci Foundation and Melagioco Foundation. The conference covered a spectrum of topics ranging from target discovery to therapeutic advances in immuno-oncology, bringing world-renowned expert

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… Anna Maria Corsale presented her data on the interplay between clonal plasma cells and the bone marrow (BM) microenvironment, which plays a crucial role in the development of multiple myeloma (MM). … The Insider: Impact of the Gut Microbiota on Cancer Immunity and Response to Therapies in Multiple Myeloma. Front Immunol. 2022;13: 845422. 35371048 10.3389/fimmu.2022.845422 PMC8968065 59. …

Лечение болезни костей миэломы: Когда, как часто и как долго?

Площадь ММ в последние годы резко изменилась. Было введено несколько новых и более эффективных методов лечения, которые не только делают пациентов более продолжительными, но и приводят их к более глубокой ремиссии. Это делает потенциальное общее воздействие защитной обработки костей гораздо более высоким, но, возможно, и менее необходимым. Введены новые и более точные методы воображения, которые делают обнаружение костных заболеваний более чувствительным, и введение критериев SLIM-CRAB изменило параметры, использовавшиеся в старых клинических испытаниях для исследования лечения костных заболев

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… Introduction Multiple myeloma Multiple myeloma (MM) is a plasma cell dyscrasia defined by clonal bone marrow plasma cells ≥10 % or biopsy-proven bony or extramedullary plasmacytoma and presence of one myeloma-defining disorder [1] . … Prolonged Use of Zoledronic Acid (4 Years) Did Not Improve Outcome in Multiple Myeloma Patients. …

Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma.

Relapsed/refractory (RR) multiple myeloma (MM) patients are a fragile population because of prolonged drug exposure and advanced age. Preserving a good quality of life is of high priority for these patients and the treatment of disease- and treatment-related complications plays a key role in their management. By preventing and limiting MM-induced complications, supportive care improves patients' outcome. Erythropoietin-stimulating agents and bisphosphonates are well-established supportive strategies, yet novel agents are under investigation, such as anabolic bone agents and activin receptor-li…

Rediscovering hemostasis abnormalities in multiple myeloma: The new era.

Multiple myeloma (MM) is a malignancy arisen from the abnormal proliferation of clonal plasma cells. It has a high risk of developing bleeding and thrombotic complications, which are related to poor prognosis and decreased survival. Multiple factors are involved in the breaking of the hemostasis balance, including disease specific factors, patient-specific factors, and drug factors that change pro-and anticoagulant and fibrinolysis. Recently, with the introduction of new treatments such as monoclonal antibodies, chimeric antigen receptor modified T-cell therapy, antibody-drug conjugates direct…

From toxicity to immunity: Evaluating CAR-T and conventional therapies in multiple myeloma through quality-adjusted life year (QALY) outcomes.

Multiple myeloma (MM) remains characterized by recurrent relapse and cumulative treatment burden despite major therapeutic advances. This study compared conventional stepwise regimens with CAR-T cell therapy in terms of QoL, toxicity, cost, and ethical considerations within a model-based comparative framework. This comparative pharmacoeconomic modeling analysis was based on published clinical trial data. Kaplan-Meier survival curves were digitized to estimate mean overall survival (OS) and progression-free survival (PFS) using area-under-the-curve integration. Treatment costs were calculated b…

Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies.

Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the main…

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities.

Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article c

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… Daratumumab binds to cluster of differentiation (CD)-38 overexpressed on multiple myeloma cells and is already marketed for the treatment of multiple myeloma with an intravenous formulation and a weight-adjusted dosing regimen [ 34 ]. … A study of subcutaneous daratumumab versus active monitoring in participants with high-risk smoldering multiple myeloma. 2017. https://clinicaltrials.gov/ct2/show/NCT03301220 . Accessed 31 Mar 2018. 37. …

IgG N-glycan Signatures as Potential Diagnostic and Prognostic Biomarkers.

IgG N-glycans are an emerging source of disease-specific biomarkers. Over the last decade, the continued development of glycomic databases and the evolution of glyco-analytic methods have resulted in increased throughput, resolution, and sensitivity. IgG N-glycans promote adaptive immune responses through antibody-dependent cellular cytotoxicity (ADCC) and complement activation to combat infection or cancer and promote autoimmunity. In addition to the functional assays, researchers are examining the ability of protein-specific glycosylation to serve as biomarkers of disease. This literature re

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… Stages of plasma cell disorders leading to multiple myeloma begin with monoclonal gammopathy of undetermined significance (MUGS), progressing to smoldering myeloma (SMM), and lastly to multiple myeloma (MM). …

Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy.

The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the incorporation of this new class of agents with current MM therapies. However, both antigens are also expressed on other normal tissues including hematopoietic lineages and immune effector cells, which may limit their long-term clinical use. B cell maturation antigen (BCMA), a transme…

Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.

Despite the vast amounts of research and remarkable discoveries that have been made in recent decades, cancer remains a leading cause of death and a major public health concern worldwide. Gossypol, a natural polyphenolic compound derived from the seeds, roots, and stems of cotton (Gossypium hirsutum L.), was first used as a male contraceptive agent. Due to its diverse biological properties, including antifertility, antiviral, antioxidant, antibacterial, antimalarial, and most notably antitumor activities, gossypol has been the subject of numerous studies. Nevertheless, no systematic review has

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… Multiple Myeloma Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells. Growing data suggests that the microenvironment of tumor cells in the bone marrow plays a key role in the pathogenesis [ 95 ]. … According to a multistep development model, monoclonal gammopathy with unknown clinical relevance can advance to smoldering multiple myeloma, symptomatic intramedullary and extramedullary multiple myeloma, or plasma cell leukemia [ 96 ]. …

Nonsteroidal Anti-Inflammatory Drugs as Modulators of Cation Channels: Fenamates Repurposing in Channelopathies.

Cationic ion channels are transmembrane proteins that regulate the flux of cations (potassium, sodium, and calcium) across cell membrane, playing a pivotal role in many cellular functions. Disruptions of their activity can lead to the so-called genetic or acquired channelopathies, a heterogeneous group of diseases that affect multiple human systems. Fenamates, a class of nonsteroidal anti-inflammatory drugs, has recently emerged as modulators of cationic ion channels highlighting the possibility of their repurposing for the treatment ion channel-related disorders, such as channelopathies, chro

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… myeloma, [ 7 , 8 , 9 , 10 – 12 ] and also in neurodegenerative diseases or autoimmunity, [ 13 , 14 ] leading to the definition of acquired channelopathies. … Her research has focused on solid and hematologic tumors, particularly multiple myeloma, investigating the bone marrow microenvironment to identify novel therapies and mechanisms of drug resistance. …

Doubly blind: a systematic review of gender in randomised controlled trials.

BackgroundAlthough observational data show social characteristics such as gender or socio-economic status to be strong predictors of health, their impact is seldom investigated in randomised controlled studies (RCTs).Objective & designUsing a random sample of recent RCTs from high-impact journals, we examined how the most often recorded social characteristic, sex/gender, is considered in design, analysis, and interpretation. Of 712 RCTs published from September 2008 to 31 December 2013 in the Annals of Internal Medicine, British Medical Journal, Lancet, Canadian Medical Association Journal, or

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… with lower hematocrit had significantly better outcomes, i.e. fewer deaths from cardiovascular or thrombotic events | N =365 Women=38% | No comment on whether smaller hematocrit elevations have greater impact on health of women Mateos (industry) ( 52 ) | Comparison of drug to no drug for smouldering multiple … Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369:438–47. doi: 10.1056/NEJMoa1300439. 53. Milstone AM, Elward A, Song X, Zerr DM, Orscheln R, Speck K, et al. …

Brazilian consensus recommendations on the diagnosis and treatment of light chain amyloidosis.

INTRODUCTION: Systemic immunoglobulin light chain amyloidosis is characterized by the extracellular deposition of misfolded light chains, leading to progressive dysfunction of multiple organs. Diagnosis remains a significant clinical challenge and is frequently delayed due to the presence of nonspecific symptoms, coupled with limited access to specialized diagnostic tools and expertise. Currently, no established national recommendations for the diagnosis and management of this condition exist in Brazil. METHODS: These expert recommendations were developed following a structured advisory meeti

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… Pre-existing plasma cell dyscrasias, including MGUS and multiple myeloma, carry a significant risk of progression to AL amyloidosis [ 10 , 11 ]. … Management of AL amyloidosis involves supportive care and plasma cell-targeting therapies derived from multiple myeloma protocols, utilizing a similar risk-adapted approach [ 52 ]. …

sCD25 as an independent adverse prognostic factor in adult patients with HLH: results of a multicenter retrospective study.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but often fatal hyperinflammatory syndrome caused by an inborn or acquired error of immunity. In adults, the underlying immunodeficiency generally arises alongside severe infections, malignancies, autoimmune diseases, and immunosuppressive treatment. To analyze risk factors and outcome in adults, we conducted a multicenter retrospective study. A total of 62 adult (age ≥18 years) patients met at least one of the following inclusion criteria: (1) ≥5 of 8 HLH-2004 criteria, (2) HScore ≥ 200 plus 4 HLH-2004 criteria, or (3) mutation compatible wit

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… Etiologies Etiology n (%) Comment Malignancies 22 (35) Myeloid 2 (3) AML 1 (2) MDS 1 (2) B-lymphoid 11 (18) Hodgkin lymphoma 4 (6) EBV association n = 4 DLBCL 3 (5) EBV association n = 2 B-cell lymphoma 1 (2) Primarily cerebral B-cell lymphoma 1 (2) Multiple myeloma 2 (3) After autologous SCT n = 2 T … myeloma | 2 | (3) | After autologous SCT n = 2 T/NK-lymphoid | 8 | (13) | T/NK-cell lymphoma | 2 | (3) | PTCL-NOS | 2 | (3) | Angioimmunoblastic T-cell lymphoma | 1 | (2) | EBV association Mycosis fungoides | 1 | (2) | NK-cell leukemia | 1 | (2) | EBV association T-cell neoplasia (not further classified …

Навигация терапевтического ландшафта миеломы: иммунотерапия, микроокружающая среда и сопротивление.

Иммунотерапии, включая клетки химерика антигенного рецептора (CAR) T, биконкретные Т-клеточные агенты (BITEs) и антитело-наркотики (ADC), изменили ландшафт лечения множественной миеломы (MM). Несмотря на высокие показатели первоначальных ответов, достижение долговременной ремиссии по-прежнему сопряжено с трудностями из-за частых рецидивов, вызванных комплексными механизмами терапевтического сопротивления. В этом обзоре мы всесторонне исследуем врожденную устойчивость к опухоли, такую, как врожденный и приобретенный антигенный выход, обусловленный геномными изменениями, структурными вариациями …

Myeloma Bone Disease: A Comprehensive Review.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells in the bone marrow microenvironment, characterized by overproduction of heavy- and light-chain monoclonal proteins (M-protein). These proteins are mainly found in the serum and/or urine. Reduction in normal gammaglobulins (immunoparesis) leads to an increased risk of infection. The primary site of origin is the bone marrow for nearly all patients affected by MM with disseminated marrow involvement in most cases. MM is known to involve bones and result in myeloma bone disease. Osteolytic lesions are seen in 80% of patien…

The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.

Adenosine, an immunosuppressive metabolite, is produced by adenosine triphosphate (ATP) released from dying or stressed cells and is found at high levels in the tumor microenvironment of most solid tumors. It mediates pro-tumor activities by inducing tumor cell proliferation, migration or invasion, tumor tissue angiogenesis, and chemoresistance. In addition, adenosine plays an important role in regulating anti-tumor immune responses and facilitating tumor immune escape. Adenosine receptors are broadly expressed by tumor-infiltrated immune cells, including suppressive tumor-associated macrophag

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… Studies have shown that CD38 is highly and uniformly expressed at the cell surface of multiple myeloma (MM) cells, and monoclonal antibodies against CD38 are highly efficacious in the treatment of MM [ 140 , 141 , 142 ]. … Myeloma | DRUG: Talquetamab|DRUG: Belantamab Mafodotin | PHASE3 | 20 October 2022 NCT05572515 | Relapsed or Refractory Multiple Myeloma | DRUG: Teclistamab|DRUG: Pomalidomide|DRUG: Bortezomib|DRUG: Dexamethasone|DRUG: Carfilzomib | PHASE3 | 29 March 2023 NCT04270409 | Plasma Cell Myeloma | DRUG: Isatuximab …

Cryoglobulinemia: An update on classification, pathophysiology, clinical presentation, and management.

Cryoglobulinemia (CG) is defined by the presence of serum immunoglobulins that precipitate below 37°C and redissolve upon rewarming. It is classified into three types based on immunoglobulin composition. Type I, a rare form, involves monoclonal IgM or IgG and is linked to lymphoproliferative disorders. Types II and III are known as mixed CG (MC): Type II consists of polyclonal IgG and monoclonal IgM with rheumatoid factor (RF) activity, whereas Type III includes polyclonal IgG and polyclonal IgM with RF activity. MC is predominantly associated with hepatitis C virus (HCV) infection and involve

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… These include monoclonal gammopathy of undetermined significance (MGUS), Waldenström's macroglobulinemia (WM), multiple myeloma (MM), non‐Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) [ 1 , 3 , 4 , 5 ]. … Type I cryoglobulinemia in multiple myeloma, a rare entity: analysis of clinical and biological characteristics of seven cases and review of the literature . …

Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses.

Misfolding and extracellular deposition of proteins is the hallmark of a heterogeneous group of conditions collectively termed protein misfolding and deposition diseases or amyloidoses. These include both localized (e.g. Alzheimer's disease, prion diseases, type 2 diabetes mellitus) and systemic amyloidoses. Historically regarded as a group of maladies with limited, even inexistent, therapeutic options, some forms of systemic amyloidoses have recently witnessed a series of unparalleled therapeutic successes, positively impacting on their natural history and sometimes even on their incidence. I

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… AL, immunoglobulin light chain amyloidosis; CLL, chronic lymphocytic leukemia; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; PCL, plasma cell leukemia; WM, Waldenström macroglobulinemia. … Seeking light-chain amyloidosis very early: The SAVE trial—identifying clonal lambda light chain genes in patients with MGUS or smoldering multiple myeloma. J. Clin. Oncol. 37 (15_suppl), 8010–8010. 10.1200/JCO.2019.37.15_suppl.8010 Zingraff J. J., Noel L. …