Результаты поиска

Переход (iCT) к протеазонной ингибиторной терапии: общинный подход к управлению несколькими миеломами.

Долгосрочное протеиновое ингибиторное лечение (ПИ) может улучшить множественные результаты миэломы (ММ), однако это может быть трудно достичь в клинической практике из-за токсичности, комординации и бремени многократного родительского управления. США MM-6 (В тыс.NCT03173092) зачисленные пациенты, имеющие право на трансплантацию, с новым диагнозом MM для получения ixazomib-lenalidomide-dexamethasone (IRd); ≤39 циклы или до продвижения или токсичности) после three циклы впрыскивания на основе борцезомида. Первичная конечная точка: 2- годовое безподвижное выживание (ПМС). Ключевые вторичные/экспе

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network.

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.

Burden of Disease, Treatment Patterns, and Healthcare Resource Utilization in Multiple Myeloma in the Middle East and North Africa Region: A Targeted Literature Review.

Globally, the multiple myeloma (MM) landscape varies widely, with incidence, treatment patterns, outcomes, and healthcare resource utilization (HCRU) differing across countries and regions. Many factors contribute to these differences, including ethnicity, awareness, and socioeconomic influences. This is the first analysis aiming to explore factors associated with myeloma incidence and patient characteristics in the Middle East and North Africa (MENA) region. A literature search was conducted using PubMed and Embase from 1 January 2015 to 30 May 2025. Articles reporting outcomes of interest in

Изменяющийся ландшафт терапии обслуживания в новой диагностированной миеломе: систематический обзор с сетевым мета-анализом европейской сети " Миелома " (ЕМН).

Мы провели всеобъемлющий обзор мета- и сетевого метаанализа исследований в области терапии. Леналидомид, протеиновые ингибиторы, а также CD38 антитела улучшили выживание без прогрессирования (PFS). Вместе с тем общее пособие по выживанию (ОС) появилось только при наличии линалидомида у пациентов, имеющих право на трансплантацию (ТЕ), в то время как CD38-directed Терапия показала тенденцию к улучшению ОС, не наблюдаемой с протеаозными ингибиторами. Сетевой метаанализ расценил режим против наблюдения: Daratumumumab-lenalidomide (DR) получил наибольшую пользу от PFS, за которым последовали карфил

:: < < Действенность и безопасность антителных препаратов > > (BCMA) в программе < < Развитие против рака: систематический обзор > > .

В качестве перспективных методов лечения повторной/охлажденной множественной миеломы (RRMM) появились антителные антигены (BCMA), ориентированные на антитела-наркотики (ADC). Цель этого исследования заключалась в обобщении имеющихся данных о безопасности и эффективности БКМА-АДЦ в процессе разработки системы RRM.MetodsA систематического поиска. six Библиографические базы данных и клинические анализы.gov до ноября 2024. Исследования имеют право на проведение таких исследований, если они являются клиническими испытаниями человека или исследованиями животных с оценкой БЦМА-АЦД, и если они содержа

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… In parallel, combination strategies have produced clinically meaningful improvements, with belantamab-based triplets alongside immunomodulatory imide drugs (IMiDs) or PIs prolonging progression-free and overall survival. …

How should we choose optimal salvage treatments following BCMA-directed CAR T-cell therapy?

B-cell maturation antigen (BCMA) directed chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment of relapsed/refractory multiple myeloma (RRMM), yet relapse is still common for most patients. A variety of different salvage treatment strategies have been studied in the last several years to address several resistance mechanisms that lead to relapse after BCMA CAR-T. To date, there are no clear guidelines regarding treatment sequencing strategies for salvage therapy. This review will investigate the current landscape of available salvage therapies and data supporting thei

Stem Cells Collection and Mobilization in Adult Autologous/Allogeneic Transplantation: Critical Points and Future Challenges.

Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize colle

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… However, randomized clinical studies investigating standard induction triplets with or without daratumumab in MM patients showed higher use of plerixafor and lower stem cell yields in patients receiving daratumumab, regardless of the mobilization strategy adopted [ 62 ]. 1.6. …

IgG replacement in multiple myeloma.

T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation t

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… Conventional therapies (e.g., triplets, quadruplets) Patients with newly diagnosed MM are vulnerable to infections and early mortality. Population-level data reported an early mortality rate between 10% within 60 days to 28% within 1 year [ 15 , 16 ]. …

The Role of DNA Repair in Genomic Instability of Multiple Myeloma.

Multiple Myeloma (MM) is a B cell malignancy marked by genomic instability that arises both through pathogenesis and during disease progression. Despite recent advances in therapy, MM remains incurable. Recently, it has been reported that DNA repair can influence genomic changes and drug resistance in MM. The dysregulation of DNA repair function may provide an alternative explanation for genomic instability observed in MM cells and in cells derived from MM patients. This review provides an overview of DNA repair pathways with a special focus on their involvement in MM and discusses the role th

Therapeutic Antibodies in Cancer Treatment in the UK.

The growing understanding of the molecular mechanisms of carcinogenesis accelerated the development of monoclonal therapeutic antibodies to specifically target multiple cancer pathways. Recombinant protein therapeutics now constitute a large proportion of yearly approved medicines. Oncology, autoimmune diseases and to a smaller degree the prophylaxis of organ transplant rejection are their main application areas. As of the date of this review, 37 monoclonal antibody products are approved for use in cancer treatments in the United Kingdom. Currently, the antibody therapeutics market is dominate

Bone Disease in Multiple Myeloma: Biologic and Clinical Implications.

Multiple Myeloma (MM) is a hematologic malignancy characterized by the proliferation of monoclonal plasma cells localized within the bone marrow. Bone disease with associated osteolytic lesions is a hallmark of MM and develops in the majority of MM patients. Approximately half of patients with bone disease will experience skeletal-related events (SREs), such as spinal cord compression and pathologic fractures, which increase the risk of mortality by 20-40%. At the cellular level, bone disease results from a tumor-cell-driven imbalance between osteoclast bone resorption and osteoblast bone form

The CoV-2 outbreak: how hematologists could help to fight Covid-19.

COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in

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… Identification of biomarkers and drug repurposing candidates based on an immune-, inflammation- and membranous glomerulonephritis-associated triplets network for membranous glomerulonephritis. BMC Med. Genomics. 2020;13(1):5. doi: 10.1186/s12920-019-0655-8. 69. …

XPO1: From basic research to clinical treatment (Review).

Exportin 1 (XPO1) is a key nuclear export receptor that mediates the nuclear export of tumor suppressor proteins and growth‑regulatory mRNAs from the nucleus to the cytoplasm. In several types of cancer, XPO1 is overexpressed or hyperactivated, leading to aberrant cytoplasmic sequestration of key tumor suppressors such as p53, p21, p73, FOXO and Rb. This mislocalization abrogates their nuclear transcriptional functions, disrupting cell cycle arrest, apoptosis and DNA repair, thereby promoting uncontrolled proliferation, survival and therapy resistance. Targeting XPO1 with selective inhibitors

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

Selective molecular inhibition of the HDAC6 ZnF-UBP binding domain impairs multiple myeloma cell function.

Multiple myeloma is a plasma cell malignancy with a poor prognosis despite the recent development of new therapeutic options. Histone deacetylase 6 (HDAC6) is overexpressed in multiple myeloma cells and may be involved in the acquisition of resistance to conventional anti-proteasome treatments. In addition to displaying a deacetylase catalytic activity, HDAC6 plays an essential role in the regulation of autophagy and cell death by recognizing ubiquitinated motifs from misfolded proteins through its C-terminal ZnF-UBP binding domain. These defective proteins are sent to the aggresome to facilit

The Challenging Approach to Multiple Myeloma: From Disease Diagnosis and Monitoring to Complications Management.

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs t

Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.

BackgroundMCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).MethodsBinding of ABBV-467 to human MCL-1 was assessed in multiple cell lines. The ability of ABBV-467 to induce tumor growth inhibition was investigated in xen

Current status and updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland.

The availability of drugs such as thalidomide, bortezomib and lenalidomide changed the landscape in myeloma treatment and has extended the median survival up to 10 years with a substantial improvement in quality of life. This development prompted a Swiss expert panel to re-evaluate the current status and formulate updated clinical recommendations for the diagnosis and treatment of plasma cell myeloma. These recommendations should help clinicians in their decision making to achieve the best outcome based on currently available data.

Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib.

Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit β5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route i

Repurposed Drugs in Gastric Cancer.

Gastric cancer (GC) is one of the major causes of death worldwide, ranking as the fifth most incident cancer in 2020 and the fourth leading cause of cancer mortality. The majority of GC patients are in an advanced stage at the time of diagnosis, presenting a poor prognosis and outcome. Current GC treatment approaches involve endoscopic detection, gastrectomy and chemotherapy or chemoradiotherapy in an adjuvant or neoadjuvant setting. Drug development approaches demand extreme effort to identify molecular mechanisms of action of new drug candidates. Drug repurposing is based on the research of