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Воздействие комплексной медицинской помощи на процесс реабилитации пациентов с множественными миеломами в академическом отделении гематологии.

Множественная миелома (ММ) — сложная гематологическая гелингология, часто связанная с осложнениями и проблемами восстановления. Исследования, посвященные конкретным последствиям и факторам, связанным с применением комплексного режима ухода за больными пациентами с множественной миеломой в отделении гематологии, по-прежнему носят ограниченный характер. Изучить положительные аспекты потенциальной пользы всеобъемлющей модели ухода за больными. Сбор клинических данных о пациентах с множественными миеломами, которые с марта проходили обычную химиотерапию в отделении гематологии нашей больницы 2020 …

Немецкий многоцентральный анализ талькетамаба в реальном мире 138 - пациенты с повторной/реактивной миеломой.

Удельные Т-клиники (ББТЦ) представляют собой изменение парадигмы в подходе к повторной/охлажденной миеломе (RRMM). Talquetamab, GPRC5DxCD3 BTCE, продемонстрировал многообещающие результаты: MonumenTAL-1 и недавно был одобрен Администрацией продовольствия и лекарств и Европейским агентством по медицине. Однако лечение в реальных условиях может не представлять собой характеристику пациента при клинических испытаниях с ограниченными критериями охвата. Мы провели ретроспективный анализ реального мира, включая 138 Пациенты БРМ лечили талькетамабом 21 Немецкие центры. Излечимых пациентов, 43% ISS II

Совпадение в аннотации оригинала
Bispecific T-cell engagers (BTCEs) represent a paradigm shift in the treatment of relapsed/refractory multiple myeloma (RRMM). Talquetamab, a GPRC5DxCD3 BTCE, has shown promising results in the MonumenTAL-1 trial and was recently approved by the Food and Drug Administration and the European Medicines Agency. However, treatment under real-world conditions may…

Population Pharmacokinetics for Belantamab Mafodotin Monotherapy and Combination Therapies in Patients with Relapsed/Refractory Multiple Myeloma.

BACKGROUND AND OBJECTIVE: Belantamab mafodotin is an antibody-drug conjugate (ADC) comprising a monoclonal antibody targeting B-cell maturation antigen (BCMA) conjugated to the microtubule inhibitor monomethyl auristatin F via a protease-resistant maleimidocaproyl linker (cysteine maleimidocaproyl monomethyl auristatin F [cys-mcMMAF]). Belantamab mafodotin monotherapy population pharmacokinetics (PopPK) were previously described in relapsed/refractory multiple myeloma (RRMM). This analysis aimed to further characterize the PopPK of belantamab mafodotin ADC and cys-mcMMAF when administered intr…

The ADAR1-regulated cytoplasmic dsRNA-sensing pathway is a novel mechanism of lenalidomide resistance in multiple myeloma.

Immunomodulatory drugs (IMiDs) are a major class of drugs for treating multiple myeloma (MM); however, acquired resistance to IMiDs remains a significant clinical challenge. Although alterations in cereblon and its pathway are known to contribute to IMiD resistance, they account for only 20% to 30% of cases, and the underlying mechanisms in the majority of the resistance cases remain unclear. Here, we identified adenosine deaminase acting on RNA1 (ADAR1) as a novel driver of lenalidomide resistance in MM. We showed that lenalidomide activates the MDA5-mediated double-stranded RNA (dsRNA)-sensi…

Целевое воздействие на ось MARCH5-MFN2 для усиления фузии митохондрий и чувствительности клеток множественной миеломы к венетоклаксу.

ОБЗОР: Накопленные данные указывают на то, что события физиологического деления и слияния митохондрий нарушены в раке из-за нарушения функции их ключевых регуляторов. В данном исследовании мы изучали функциональную роль E3-убиквитин-лигазы Мембранный ассоциированный Ринг-Ч-Тип Фингер 5 (MARCH5) в регуляции роста клеток, метаболической переработки и устойчивости к лекарствам в мультиплексной миеломе (ММ) через отрицательную регуляцию драйвера слияния митохондрий митофузина 2 (MFN2). МЕТОДЫ: Вiability клеток и апоптоз оценивались в линиях клеток ММ или в кокультуре с стромальными клетками с исп

Совпадение в аннотации оригинала
BACKGROUND: Accumulating evidence suggests that mitochondrial fission and fusion events are imbalanced in cancer due to defective activity o … CH-Type Finger 5 (MARCH5) in regulating cell growth, metabolic reprogramming and drug resistance in multiple myeloma (MM) through the negative regulation of the mitochondrial fusion driver mitofusin 2 (MFN2). METHODS: Cell viability and apoptosis were evaluated in MM cell lines or in co-culture with stromal cells using the CellTiter-Glo® Cell Viability Assay and …

Daratumumab monotherapy in a patient with kappa light chain multiple myeloma and decompensated cirrhosis: a case report.

BACKGROUND: Multiple myeloma (MM) rarely presents as decompensated liver cirrhosis, posing a significant diagnostic challenge that can lead to misdiagnosis and delayed treatment. We report a case of kappa-light chain multiple myeloma (κ-LCMM) initially managed as end-stage liver disease to highlight the diagnostic pathway and a successful, organ-reversing therapeutic outcome. CASE PRESENTATION: We report the case of a 67-year-old male who presented with decompensated liver cirrhosis and refractory ascites as the initial manifestation of multiple myeloma. Serum free light chain assay revealed …

Symptom distress and fear of progression associated with quality of life in multiple myeloma patients receiving treatment

PURPOSE: Patients undergoing treatment for multiple myeloma (MM), a common hematological malignancy, may experience symptom distress, functional decline, fear of disease progression, and poor quality of life (QOL). This study of MM patients aims to assess patient-reported symptom distress, functional impairment, fear of cancer progression, and QOL and to identify factors associated with QOL. METHODS: This cross-sectional study used consecutive sampling to recruit subjects from inpatient wards and the outpatient departments of hematology and chemotherapy at a medical center in northern Taiwan.…

A Relapsing Acute Tubulointerstitial Nephritis as an Expression of a Kappa Light Chain Multiple Myeloma: A Case Report.

INTRODUCTION: Light chain-mediated acute tubulointerstitial nephritis (LCTIN) is a rare and underrecognized renal manifestation of plasma cell dyscrasias, including multiple myeloma. It presents as a dense interstitial inflammatory infiltrate involving polyclonal lymphocytes and plasma cells, often mimicking other forms of tubulointerstitial nephritis and delaying the correct diagnosis. CASE PRESENTATION: A 46-year-old man was initially managed as having drug-induced acute interstitial nephritis due to NSAID use, responding only transiently to steroids. Upon relapse with worsening kidney func…

Impact of myosteatosis on prognosis in multiple myeloma patients: A subgroup analysis of 182 cases and development of a nomogram.

BACKGROUND: This study aims to explore the prognostic value of myosteatosis in multiple myeloma (MM) and to analyze the factors influencing myosteatosis. METHODS: A retrospective analysis was conducted on 182 patients treated for MM at our institution from 2009 to 2020 who underwent MRI examinations. The fatty infiltration rate (FIR) of the erector spinae and multifidus muscles at the L3 level was measured to assess the degree of myosteatosis. Patients were grouped based on fracture presence and median FIR, and group differences were compared, with P < 0.05 considered statistically significan…

Management of Medication-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients With Pentoxifylline and Tocopherol: Case Reports.

Medication-related osteonecrosis of the jaw (MRONJ) is a well-known side effect of bone-modifying agents such as antiresorptive medications including pamidronic and zoledronic acids (intravenous bisphosphonates) and denosumab (anti-RANK ligand humanized monoclonal antibody). The major risk factor for the precipitation of MRONJ in a patient taking antiresorptive medication is dentoalveolar trauma such as dental extractions. Management of MRONJ in oncology patients is exceptionally challenging. In this report, two multiple myeloma patients with longstanding advanced-stage MRONJ were successfully…

Development of a Selective and Potent PRMT4 PROTAC Degrader with Efficacy against Multiple Myeloma in Vitro and in Vivo.

Protein arginine methyltransferase 4 (PRMT4) is highly expressed in relapsed or refractory multiple myeloma (MM) and is associated with poor prognosis. Conventional PRMT4 inhibitors face challenges including inadequate efficacy, acquired resistance, and inability to inhibit nonenzymatic functions. In this study, we developed a proteolysis targeting chimera (PROTAC) targeting PRMT4, named C199, which is composed of the PRMT4 inhibitor EZM2302, a linker, and a von Hippel-Lindau (VHL) E3 ligase ligand. C199 demonstrated potent cellular degradation (DC50 = 106 nM, Dmax = 93.1%) and showed high sel…

A network meta-analysis of randomized clinical trials in lenalidomide-exposed or -refractory multiple myeloma patients.

BACKGROUND: The treatment landscape for relapsed/refractory multiple myeloma (RRMM) is rapidly evolving, particularly for patients exposed or refractory to lenalidomide. With the aim of evaluating the relative efficacy of lenalidomide-free regimens as second-line treatment options, an updated network meta-analysis, incorporating phase II/III randomized controlled trials, has been conducted. MATERIALS AND METHODS: A systematic literature search identified eight eligible trials comprising 3952 patients. The primary outcome was progression-free survival (PFS), analyzed through Bayesian and frequ…

Clinical Practice of Treatment Switch in Transplant-eligible Patients with Multiple Myeloma: An Exploratory Retrospective Analysis.

Objective In the real-world clinical setting of transplant-eligible patients with multiple myeloma (MM), a certain proportion of patients switch from induction therapy to other regimens because of insufficient response or adverse events. However, the prognostic benefits of these changes remain unclear. This retrospective study investigated the impact of pre-transplant induction therapy switches on the prognosis. Methods We analyzed the treatment course, patient background, risk classification, and post-transplantation event-free survival (EFS) of 35 patients who achieved partial response or be…

Talquetamab for the treatment of relapsed/refractory multiple myeloma: a review of efficacy, safety, and real-world evidence.

INTRODUCTION: Talquetamab is a GPRC5DxCD3 T-cell-engaging bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma. GPRC5D represents a novel and emerging target in antimyeloma therapy, and there is substantial drug development for new therapies targeting this antigen. AREAS COVERED: Herein, we review the efficacy, safety, and future development directions of talquetamab, including emerging talquetamab-based combination regimens and ongoing clinical trials. We will also review the growing landscape of GPRC5D-targeting immunotherapies in development for multiple m…

Characterizing circulating rare cells in peripheral blood for detecting and monitoring multiple myeloma and precursor states.

Multiple myeloma (MM) arises from abnormal plasma cells (PCs) progressing from precursor states, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Understanding this transition and progression to overt MM requires improved non-invasive strategies. We employed a liquid biopsy approach to detect and characterize circulating PCs across disease states in 68 patients (MGUS = 11, SMM = 21, NDMM = 19, RRMM = 17) using multi-channel immunofluorescence staining and machine learning-assisted rare event detection. PCs were identified by CD138 and B…

Efficacy and safety of daratumumab in intermediate/high-risk smoldering multiple myeloma: final analysis of CENTAURUS.

Early intervention in smoldering multiple myeloma (SMM) may delay progression to MM. Here, we present the final analysis of the phase 2 CENTAURUS study. In total, 123 patients with intermediate/high-risk SMM were randomized to IV daratumumab 16 mg/kg after a long-intense (n = 41), intermediate (n = 41), or short-intense (n = 41) dosing schedule. At a combined median follow-up of 85.2 months, in the long-intense, intermediate, and short-intense arms complete response or better rates were 4.9%, 9.8%, and 0%; overall response rates were 58.5%, 53.7%, and 37.5%; progressive disease/death rates wer…

Genetic, epigenetic, and molecular determinants of multiple myeloma and precursor plasma cell disorders: a pathophysiological overview.

Multiple myeloma (MM) is a malignancy of clonal plasma cells that arises from precursor conditions, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Disease progression is driven by a complex interplay of genetic alterations, epigenetic dysregulation, and support from the bone marrow microenvironment. Early events such as chromosomal translocations (e.g. t(4;14)), copy number abnormalities (e.g. del(17p), gain(1q)), and driver mutations in KRAS, NRAS, TP53, and DIS3 promote clonal evolution. These are complemented by non-coding regulato…

Hepatitis B and C virus infection and risk of multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Multiple myeloma (MM) is a clonal proliferative disorder of plasma cells with limited curative options. Hepatitis B (HBV) and hepatitis C (HCV) viruses have been implicated in the development of various hematological malignancies, but their association with MM remains unclear. This systematic review and meta-analysis aimed to investigate the risk of MM in individuals with HBV and HCV infections. METHODS: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, Embase, and additional sources for cohort and case-control studies published between January…

EXCALLBER-RRMMМ: III этап испытания ибердомида, даратумумаба и дексаметасона в реанимированном/охотничьем миеломе.

Множественная миелома (ММ) — новообразование плазменных клеток, вызванное злокачественным преобразованием клональных плазменных клеток. Она характеризуется многочисленными периодами ремиссии и рецидива, требующими многообразной терапии, при этом реакция на лечение и выживание уменьшается с каждым последующим рецидивом. Для обеспечения глубокого и долговременного реагирования в случае рецидивов/отказов MM (RRMM) требуется новое лечение. Ибердомид (IBER), пероральный агент CELMODTM, связан с более сильным опухолицидным и иммуностимуляторным эффектом, чем иммуномодулирующие препараты (IMIDs). IBE…

A rare presentation of extramedullary multiple myeloma as a large gluteal soft tissue mass: A case report.

INTRODUCTION: Extramedullary multiple myeloma is a rare condition, occurring in 7 % to 18 % of cases, where malignant plasma cells spread beyond the bone marrow to various organs and soft tissues. This report presents a case of secondary extramedullary multiple myeloma with an unusual soft tissue mass, highlighting diagnostic challenges, management considerations, and the importance of early detection. CASE PRESENTATION: A 78-year-old woman with a history of multiple myeloma and AL amyloidosis presented with a rapidly enlarging, non-tender gluteal mass over the past two months. Physical exami…