Результаты поиска

Daratumumab for newly diagnosed multiple myeloma: Pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS.

BACKGROUND: Older adults with newly diagnosed multiple myeloma (NDMM) have poor prognosis and constitute a subgroup of particular interest. In the GRIFFIN (NCT02874742) and PERSEUS (NCT03710603) studies, adding daratumumab to bortezomib/lenalidomide/dexamethasone (VRd) induction/consolidation and lenalidomide (R) maintenance deepened responses and improved progression-free survival (PFS) versus VRd/R in transplant-eligible patients with NDMM. Subgroup analyses of patients aged ≥65 years in PERSEUS demonstrated less pronounced PFS benefits (HRs: 0.97 [computerized algorithm]; 0.87 [independent …

Improving predictive accuracy in multiple myeloma using a plasma cell profile derived from single-cell RNA sequencing.

Multiple myeloma (MM) shows inherent clinical and biological heterogeneity, leading to variable treatment responses and outcomes. The complex molecular landscape of MM makes precise risk stratification through clinical genetic testing difficult. Thus, identifying better biomarkers is essential to enhance existing stratification methods and guide personalized therapy decisions. Here, we systematically analyzed the intratumor heterogeneity of tumor cells from 12 newly diagnosed MM patients with different outcomes at single-cell resolution, especially those with an overall survival of less than 2…

FDA Approval Summary: Idecabtagene Vicleucel for the Treatment of Triple-Class-Exposed, Relapsed or Refractory Multiple Myeloma.

On April 4, 2024, the FDA approved idecabtagene vicleucel (ide-cel) for adults with relapsed or refractory multiple myeloma after two or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on KarMMa-3, a randomized, open-label trial in 386 patients. The study compared a single infusion of ide-cel to standard-of-care treatment consisting of the investigator's choice of five anti-myeloma regimens. The primary endpoint was progression-free survival, which was significantly longer in the ide-cel arm [HR …

Prognostic impact of focal lesion location and persistence in multiple myeloma: insights from serial PET/DWI imaging.

Multiple myeloma (MM) is a heterogeneous disease exemplified by focal lesions (FLs), densely populated nodules whose number and persistence during treatment predict poor outcome. However, the prognostic role of FL location and the relationship between FLs at different time points remain underexplored, although they may provide critical clues to disease evolution and resistance mechanisms. We analyzed positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI) scans from 243 patients with MM enrolled in total therapies at baseline, after autologous stem cell trans…

Applications and prospects of molecularly targeted drugs combined with CAR-T cell therapy to treat multiple myeloma.

Chimeric antigen receptor T (CAR-T) cell therapy, a type of precision immunotherapy, has shown promising outcomes in treating certain types … scape. Their combination has rushed into the spotlight of research on individualized treatments for multiple myeloma (MM). In the present review, we described frequently used molecularly targeted drugs in the combination of CAR-T cell therapy against MM.

Sequential Myelomatous Pleural and Pericardial Effusions in Multiple Myeloma: A Case Report Demonstrating Extended Survival with Teclistamab.

INTRODUCTION: Myelomatous pleural effusion (MPE) and pericardial involvement are rare manifestations of multiple myeloma (MM), occurring in less than 1% of cases and carrying historically poor prognoses. We present a unique case where both these rare serous cavity manifestations occurred sequentially in the same patient, demonstrating the evolving treatment landscape with novel targeted therapies. CASE PRESENTATION: A 42-year-old Asian female presented with left shoulder pain and swelling, leading to the diagnosis of IgG lambda MM with extensive extramedullary disease. After initial partial r…

Long non-coding RNA FEZF1-AS1 suppresses ferroptosis in multiple myeloma cells through KIAA1429-mediated m6A modification.

Multiple myeloma (MM) is a hematologic malignancy characterized by abnormal clonal plasma cells in the bone marrow. This study aims to investigate the mechanism by which the long non-coding RNA FEZF1 antisense RNA 1 (FEZF1-AS1) regulates ferroptosis in MM cells through KIAA1429-mediated N6-methyladenosine (m6A) modification, and to identify novel therapeutic targets for MM therapy. The expression levels of FEZF1-AS1, Vir-like m6A methyltransferase associated protein (KIAA1429, also known as also known as VIRMA), and OTU deubiquitinase, ubiquitin aldehyde-binding 1 (OTUB1) were detected by quan…

Clonal plasma cell proportion in the synthetic phase identifies a unique high-risk cohort in multiple myeloma.

Risk stratification models based on cytogenetics and disease burden help identify high-risk patients with newly diagnosed multiple myeloma (NDMM). However, some high-risk patients remain undetected. This study evaluated the prognostic utility of the proportion of clonal plasma cells in the S-phase of the cell cycle for NDMM. Patients with active multiple myeloma diagnosed between 01/01/2013 and 01/31/2023 who underwent S-phase assessment were included. The S-phase proportion was calculated by analyzing DNA content between G0/G1 and G2/M peaks. Among 823 patients, 16% (135) had S-phase ≥2% at d…

Extracellular Ubiquitin Drives M2 Macrophage Polarization in Multiple Myeloma Through JAK1/STAT3-mediated Transcriptional Activation of CXCR4.

Macrophage polarization engenders an immunosuppressive microenvironment, thereby facilitating the survival and epithelial-mesenchymal transition (EMT)-like changes of malignant plasma cells. Ubiquitin (Ub), a short polypeptide predominantly involved in proteasome-mediated protein degradation, has been detected extracellularly in body fluids. In certain diseases, it exerts immune-regulatory functions, including the modulation of macrophage polarization. Nevertheless, its immune-regulatory role in multiple myeloma (MM) remains undetermined. This study investigated the role of extracellular ubiqu…

CBX7 regulates chemotherapy-induced senescence-like growth arrest in multiple myeloma via the ERK/STAT3/PIM1 axis.

BACKGROUND: Chemotherapy incorporating the proteasome inhibitor bortezomib (BTZ) has improved outcomes for patients with multiple myeloma (MM); however, resistance to chemotherapy and disease relapse remain significant challenges, closely associated with cellular senescence. This study investigated the key drivers of myeloma cell senescence and its role in MM progression. METHODS: Flow cytometry assessed senescence-associated β-galactosidase (SA-β-gal) activity in myeloma cells from bone marrow samples of MM patients. BTZ was used to establish cell senescence model. RNA-seq identified key gen…

Active Epstein-Barr virus infection and its association with multiple myeloma: evidence from a meta-analytical perspective.

OBJECTIVES: To clarify the association between active Epstein-Barr virus (EBV) infection and the risk of multiple myeloma (MM), given longstanding uncertainty regarding EBV's etiologic contribution to plasma cell malignancies. METHODS: A meta-analysis was conducted using eight case-control studies comprising 795 MM patients and 367 controls. Active EBV infection was defined as EBV DNA positivity or EBER detection by in situ hybridization (EBER-ISH). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects and random-effects models (DerSimonian and Laird …

Undetectable Minimal Residual Disease in Multiple Myeloma: Bridging the Gap Between Clinical Trials and Real-life Application.

Much evidence supports the assessment of minimal residual disease (MRD) status in the clinical management of multiple myeloma (MM). Using highly sensitive next-generation flow cytometry and next-generation sequencing tests to detect MRD enables clinicians to evaluate the depth of response and therefore the prognosis of patients with MM as achieving deep and sustained (≥ 12 months) undetectable MRD correlates with prolonged survival in patients with MM. Because of this, undetectable MRD (also referred to as MRD-negativity) has been recognized and approved by the FDA as an early endpoint in clin…

Unveiling causal immune cell-gene associations in multiple myeloma: insights from systematic reviews and Mendelian randomization analyses.

BackgroundThe efficacy of novel chimeric antigen receptor T-cell (CAR-T) therapy is inconsistent, likely due to an incomplete understanding of the tumor microenvironment (TME). This study utilized meta-analysis to evaluate CAR-T-cell therapy efficacy and safety and employed two-sample Mendelian randomization (MR) analysis to investigate the causal links between immune cells and Multiple Myeloma (MM).MethodOur literature review, conducted from January 1, 2019, to August 30, 2024, across Medline/PubMed, Scopus, and Web of Science, identified 2,709 articles, 34 of which met our inclusion criteria…

Прогресс и перспективы на будущее в химерикском антигенном рецепторе Т-клетке и биконкретной антителной терапии для множественных миелом.

Начавшаяся терапия перенаправления Т-клеток значительно изменила условия лечения повторной/изъятий множественной миеломы (RRMM), особенно у пациентов с тремя классами обнаженных или рефрактных заболеваний. Лечение химерных антигенных рецепторов (CAR) Т-клеток и биконкретные антитела (BSAbs), которые в первую очередь нацелены на антигены созревания клеток B (BCMA), показали замечательную эффективность в ключевых испытаниях и реальных условиях мира. В последнее время группа рецепторов G с протеиновым сцеплением C 5 В качестве многообещающих вариантов были выбраны агенты D, особенно для пациентов…

A phase 2 trial of VRD induction for transplant-eligible Japanese patients with newly diagnosed multiple myeloma.

This single-arm phase 2 trial investigated the efficacy and safety of bortezomib-lenalidomide-dexamethasone (VRD) induction for transplant-eligible Japanese patients with newly diagnosed multiple myeloma. Treatment consisted of four cycles of VRD (bortezomib 1.3 mg/m2, s.c., days 1, 4, 8, 11; lenalidomide 25 mg/body/day, days 1-14; dexamethasone 40 mg/day, p.o., days 1, 4, 8, 11), stem cell mobilization with low-dose cyclophosphamide (1 g/m2, day 1) and bortezomib (1.3 mg/m2, days 4, 7), and high-dose therapy with melphalan supported by autologous peripheral blood stem cell transplantation. Pr…

Exercise and Diet Studies Among Patients Living with Multiple Myeloma: Current Evidence and Considerations of Patient Preferences.

BACKGROUND: Multiple myeloma (MM) is the second most common blood cancer after leukemia in adults. Despite advancements in treatment that have extended survival, MM remains incurable and the cancer and its treatment result in adverse acute, long-term and latent side-effects, necessitating a focus on strategies to attenuate these side-effects and improve quality of life. This narrative review highlights MM patient preferences for exercise and/or diet interventions relative to complete and ongoing interventions to identify gaps and needs for future lifestyle interventions in MM patients aimed at…

Экологические и профессиональные факторы риска, связанные с множественной миеломой: многоцентральное, больничное и параллельное исследование конкретных случаев.

ВВЕДЕНИЕ: Множественная миелома (ММ), гематологическая порча, вызванная распространением неопластических плазменных клеток, по-прежнему недостаточно характеризуется факторами профессионального и экологического риска и их воздействием на качество жизни пациентов (QoL). В этом исследовании изучается изменяемое воздействие на Западном берегу, Палестина, и оценивается их связь с рисками, связанными с ММ, и результатами по конкретным заболеваниям. МЕТОДЫ: В период между 2018 и 2025, включая 227 Пациенты ММ и 176 Совпадающие с контрольными. Спички основывались на возрасте, поле, госпитализации и тип…

Outcome of Patients With Central Nervous System Multiple Myeloma (CNS-MM) Treated With CNS-Directed Radiation Therapy.

BACKGROUND: The prognosis of multiple myeloma involving the central nervous system (CNS-MM) is poor. We report outcomes of CNS-MM treated with CNS-directed radiation therapy (RT). METHODS: We retrospectively reviewed patients with CNS-MM treated with CNS-directed RT from 2015 to 2024. CNS-MM was defined as having radiographic leptomeningeal or parenchymal disease, and/or pathologic CSF involvement. Complete response (CR) constituted having no atypical cells in CSF or resolution of radiographic disease. Otherwise, patients were categorized with partial response (PR) based on imaging, or stable…

Сердечные биомаркеры для стратификации риска в недавно диагностированном миеломе высокого риска в пробе GMG-CONCEPT.

Сердечно-сосудистые неблагоприятные явления (CVAE) являются клиническими побочными эффектами во время лечения протеаозным ингибитором карфилзомиба. Мы изучили прогнозируемую ценность сердечных биомаркеров для начала CVAE у пациентов с недавно поставленным диагнозом множественной миэломы повышенного риска, обработанных изатуксимабом, карфиломибом, линалидомидом и дексаметазоном в исследовании GMG-CONCEPT (GMG-CONCEPT).NCT03104842). Пациенты, включенные в это перспективное, многоцентровое корреляционное исследование, имеют право на получение пробы сыворотки до начала лечения и на ≥ 1 позднее был

Совпадение в аннотации оригинала
Cardiovascular adverse events (CVAE) are clinically relevant side effects during treatment with the proteasome inhibitor carfilzomib. We investigated the predictive value of cardiac biomarkers for onset of CVAE in patients with newly diagnosed high-risk multiple myeloma treated with isatuximab, carfilzomib, lenalidomide, and dexamethasone in the GMMG-CONCEPT…

Скрытые расходы PEG-rhG-CSF на аутлогическую трансплантацию стволовых клеток для недавно диагностированной множественной миеломы.

Оценить клиническую ценность полиэтилен-гликолизированного рекомбинированного человеческого гранулоцита-стимулирующего фактора (PEG-rhG-CSF) для гематопоэтического восстановления после аутологической трансплантации стволовых клеток (ASCT) у недавно диагностированных пациентов с множественными миеломами (NDMM). В настоящем исследовании анализируются данные, полученные от 70 Пациенты NDMM, проходящие ACCT, с 33 получение PEG-rhG-CSF и 37 Принимаю RG-CSF. Среднее время нейтрофильного и тромбоцитного оплодотворения, медианное переливание продуктов крови, неблагоприятные реакции, связанные с лечени

Совпадение в аннотации оригинала
To evaluate the clinical value of polyethylene glycolized recombinant human granulocyte-stimulating factor (PEG-rhG-CSF) for hematopoietic reconstitution after autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (NDMM) patients. This study analyzed data from 70 NDMM patients undergoing ASCT, with 33 receiving PEG-rhG-CSF and 37 re…