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Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives.

The treatment landscape for patients with multiple myeloma (MM) is constantly evolving. Over the past decade, the introduction of novel agents such as proteasome inhibitors and immunomodulatory drugs has led to notable changes in therapeutic strategy, and improvements in survival, yet MM remains incurable in the vast majority of cases. More recently, a targeted approach to MM treatment has emerged, using monoclonal antibodies (mAbs) to target antigens expressed on the surface of MM cells. MAbs tested to date kill MM cells via the host's immune system and/or by promoting apoptosis, and appear t

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… Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma . Blood 2014 ; 123 : 4136 –4142. 24833354 10.1182/blood-2013-12-546374 PMC4123433 Thomas SK, Suvorov A, Noens L, Rukavitsin O, Fay J, Wu KL et al. … Comparative analysis of multiple myeloma treatment by CD138 antigen targeting with bismuth-213 and Melphalan chemotherapy . Nucl Med Biol 2014 ; 41 : e30 –e35. 24759272 10.1016/j.nucmedbio.2014.02.008 Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H et al. …

Treatment of Smoldering Multiple Myeloma: Ready for Prime Time?

The current standard of care for smoldering multiple myeloma (SMM) is observation until there is end-organ involvement. With newer and more effective treatments available, a question that is increasingly asked is whether early intervention in patients with SMM will alter the natural history of their disease. Herein, we review the evolving definition of SMM and risk stratification models. We discuss evidence supporting early intervention for SMM-both as a preventative strategy to delay progression and as an intensive treatment strategy with a goal of potential cure. We highlight ongoing trials

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… These included studies comparing observations vs. treatment with melphalan and prednisone [ 37 , 38 ], bisphosphonates [ 39 , 40 ], or thalidomide [ 41 , 42 , 43 ]. Compared to observation alone, these early studies, however, did not result in any noticeable clinical benefit. … In the phase II GEM-CESAR trial, six cycles of KRd induction were followed by high-dose melphalan and ASCT, and consolidation with KRd for two cycles, then Rd maintenance for 2 years in 90 patients with SMM whose risk was identified as >50% progression at 2 years [ 48 ]. …

Смертельная диспропорция фусариоза во время вводного терапия для взрослой острой лимфоболической лейкемии у пациента с приорной множественной миеломой.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

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… He received bortezomib, thalidomide, and dexamethasone plus radiotherapy, followed by high-dose melphalan and autologous stem cell transplantation, achieving a very good partial response. … Previous melphalan and lenalidomide exposure may increase the risk of second hematologic malignancies, although B-ALL is rare (<1%) 19 Reported B-ALL cases after lenalidomide therapy appear clonally distinct from the underlying plasma cell disorder, supporting an independent leukemogenic event. 20 …

A Survey Study of Patient-Physician Communication and Treatment Decision-Making Preference at Treatment Initiation and After Disease Stabilization in Newly Diagnosed Multiple Myeloma.

INTRODUCTION: We present real-world evidence of patient-physician communication for patients with newly diagnosed multiple myeloma (NDMM) who have not received hematopoietic stem cell transplantation. METHODS: An observational survey study was conducted in Japan (September‒November 2024). Patients with NDMM completed a self-reported 34-item survey (online or paper-based), and hematologists treating patients with multiple myeloma completed a self-reported 18-item survey online. Communication status between patients and physicians and information on patients' treatment expectations, values, emo

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… Abbreviations: Bd, bortezomib, dexamethasone; DLd, daratumumab, lenalidomide, dexamethasone; D‐MPB, daratumumab, melphalan, prednisolone, bortezomib; Ld, lenalidomide, dexamethasone. a n = 212. b Regimen abbreviations are per the Japanese guidelines. … The Japanese clinical practice guidelines for hematological malignancies list DLd and D‐MPB (daratumumab, melphalan, prednisolone, bortezomib) as the recommended standard‐of‐care regimen for patients with transplant‐ineligible MM; other treatments include Ld, MPB (melphalan, prednisolone, bortezomib) …

Трансплантация аутологической стволовой клетки в повторной/отправленной миеломе: долговременная эффективность и результаты безопасности из одного центра реального мира.

Справочная информация: В эпоху новой иммунотерапии в настоящее время пересматривается роль спасательной аутологической трансплантации стволовых клеток (ASCT) в многократной миэломе (R/R MM). Мы провели оценку долгосрочной эффективности и безопасности аварийно-спасательных операций в реальной одноцентристской группе. Методы: В период с марта 2012 года по август 2025 года мы ретроспективно проанализировали 57 пациентов с R/R MM, которые были спасены ASCT. Была проведена оценка клинических характеристик, реакции на лечение, токсинов, выживаемости без прогрессирования (ПФС), общего выживаемости (О

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… Nevertheless, high-dose melphalan-based consolidation supported by ASCT remains an important component of frontline therapy in eligible patients [ 4 ]. … Although the melphalan dose was reduced to 140 mg/m 2 in 38.6% of patients because of renal impairment or frailty, dose reduction was not significantly associated with survival. …

Подгруппы &quot; Frail &quot; определяют разнородные результаты у пожилых пациентов с NDMM: долгосрочные последующие мероприятия в связи с HOVON 143 суд.

В то же время в клинических испытаниях часто отсутствуют оценки слабостей. Таким образом, данные об эффективности и терпимости новых методов лечения для больных со слабым здоровьем по-прежнему являются недостаточными. Кроме того, среди слабых пациентов наблюдается значительная неоднородность, причем некоторые из них классифицируются как слабые исключительно по причине возраста (см.>80 ) и другие причины, связанные с гериатрическими расстройствами и/или коморбидами. Насколько нам известно, ХОВОН 143 Это было первое испытание, которое было специально рассчитано на слабых пациентов с недавно пост

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… In this study, patients treated with daratumumab-bortezomib-melphalan-prednisone had a substantially lower 3-year PFS rate of ∼40% in the frail subgroup compared with those treated with DRd. 19 However, differences in frailty levels because of having used the SFI in both registration trials vs the IMWG-FI … Daratumumab plus bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of ALCYONE. Clin Lymphoma Myeloma Leuk. 2021;21(11):785–798. doi: 10.1016/j.clml.2021.06.005. 20. …

Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial.

The safety and efficacy of siltuximab (CNTO 328) was tested in combination with lenalidomide, bortezomib and dexamethasone (RVD) in patients with newly-diagnosed, previously untreated symptomatic multiple myeloma. Fourteen patients were enrolled in the study, eleven of whom qualified to receive therapy. A majority of patients (81.8%) completed the minimal number or more of the four required cycles, while two patients completed only three cycles. The maximum tolerated dose (MTD) of siltuximab with RVD was dose level -1 (siltuximab: 8.3 mg/kg; bortezomib: 1.3 mg/m(2); lenalidomide: 25 mg; dexame

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… There is an increased incidence of infections associated with siltuximab, as 29% grade ⩾3 infections were observed when combined with bortezomib-melphalan-prednisone (VMP) compared with only 17% with VMP alone, and 62% when siltuximab was combined with bortezomib versus 49% for bortezomib alone. … Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma. Blood 2014; 123: 4136–4142. Orlowski RZ, Gercheva L, Williams C, Sutherland H, Robak T, Masszi T et al. …

Enteral versus parenteral nutrition in auto-HCT: a randomized controlled trial on clinical outcomes and gut microbiome dynamics.

Disruption of the gut microbiome is a common consequence of chemotherapy, linked with detrimental treatment outcomes (e.g. sepsis), especially in haematopoietic stem cell transplant (HCT) recipients. Preclinical data suggest that enteral nutrition (EN) is superior to parenteral nutrition (TPN), minimising gut atrophy and promoting eubiosis; yet, TPN continues to be used. Here, we evaluated the clinical effects of EN and TPN in autologous HCT recipients and their influence on gut microbiome dynamics. Despite efforts to optimise delivery, EN was poorly tolerated and ultimately proved unfeasible.

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… Materials and methods Study design and participants From September 2014 to January 2018, all patients ≥ 18 years subsequently referred to the Radboud University Medical Center Nijmegen in the Netherlands for auto-HCT with either high-dose melphalan (HDM) or carmustine, etoposide, cytarabine and melphalan … Table 1 Patient demographics and clinical characteristics at baseline TPN total parenteral nutrition, EN enteral nutrition, BMI body mass index, MUAC mid-upper-arm circumference, MM multiple myeloma, NHL non-Hodgkin lymphoma, HDM high-dose melphalan, BEAM carmustine, CRP C-reactive protein, GFR glomerular …

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 week

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… After high dose melphalan and autologous hematopoietic stem cell transplantation (ASCT), OM is seen in 90% of the patients, with severe forms in 46% of the patients [ 1 ]. It is clinically characterized by erythema, edema, and ulcerations and negatively affects patients’ quality of life. … Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy–European Blood and Marrow Transplantation Mucositis Advisory Group. J Clin Oncol. 2008;26(9):1519–1525. doi: 10.1200/JCO.2007.13.6028. 2. …

Lenalidomide versus lenalidomide + dexamethasone prolonged treatment after second-line lenalidomide + dexamethasone induction in multiple myeloma.

Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to

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… Aschan , et al. 2014 Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma – a retrospective population based study of 1162 patients . Eur. J. Haematol. 92 : 19 – 25 . 24118547 10.1111/ejh.12213 3 McCormack , P. … Richardson , et al. 2016 Lenalidomide (LEN) maintenance (MNTC) after high‐dose melphalan and autologous stem cell transplant (ASCT) in multiple myeloma (MM): a meta‐analysis (MA) of overall survival (OS) . Paper presented at Annual Meeting of American Society of Clinical Oncology (ASCO). …

Daratumumab monotherapy in relapsed and refractory multiple myeloma patients with severely compromised forced expiratory volume in one second.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

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… The patient was initially treated with nine cycles of bortezomib, melphalan, and prednisone, which resulted in relapsed and refractory responses. … The patient was treated with two cycles of bortezomib, melphalan, and prednisone, followed by autologous stem cell transplantation and tandem allogeneic stem cell transplantation as the first-line treatment. Eight cycles of bortezomib and dexamethasone were administered for the first relapse. …

Multiple myeloma and bisphosphonate-related osteonecrosis of the mandible associated with dental implants.

Multiple myeloma (MM) is a malignant plasma cell disorder and more than 30% of patients with this pathology develop osteolytic lesions in the jaw. Either pamidronate or zoledronic acid is recommended in patients with MM who have one or more lytic lesions. However, bisphosphonate-related osteonecrosis of the jaws (BRONJ) has been described as a complication associated with their use. Otherwise, the use of endosseous implants in oral rehabilitation is a well-established procedure, with good long-term success although systemic factors may affect the bone healing around dental implants. We report

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… As induction therapy, the treatment included six alternating cycles of vincristine, carmustine, melphalan, cyclophosphamide, prednisone (VBMCP) and vincristine, carmustine, doxorubicin and dexamethasone (VBAD) (each five/four weeks, resp.), ending in July 2007. … Consolidation therapy consisted in melphalan, alpha interpheron 2b, and autologous stem cell transplantation, carried out in October 2007. The patient also received 17 doses of Zoledronic Acid (4 mg/dose, once per month). …

Прогнозирующее значение SGK1: Ретроспективное исследование в одном центре.

Цель Это исследование направлено на оценку прогнозируемого значения сыворотки/глюкокортикоидной киназы 1 (SGK1) выражение в периферийных моноядерных клетках крови (PBMC) нескольких миеломных (MM) лиц, проходящих автологическую трансплантацию гематопоиетических стволовых клеток (AHSCT) по сравнению с традиционными минимальными остаточными заболеваниями (MRD) и оценками бесперебойной цепи света (SFLC). 85 Лица, которые прошли курс AHSCT. Выражение генов SGK1 измерялось в PBMC с использованием количественных ПЦР в режиме реального времени (qRT-PCR) в исходных условиях и в определенных интервалах

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… Treatment regimens were standardized across groups, consisting of induction with VRD (bortezomib, lenalidomide, and dexamethasone), PAD (bortezomib, doxorubicin, and dexamethasone), or VTD (bortezomib, thalidomide, and dexamethasone), then by high‐dose melphalan (200 mg/m 2 ) conditioning and post‐transplant … This was followed by a high‐dose melphalan conditioning regimen (200 mg/m 2 ) in preparation for AHSCT. Mobilization of peripheral blood stem cells was achieved using granulocyte colony‐stimulating factor (G‐CSF), with cyclophosphamide used optionally. 2.4. …

Лечение пациентов с гематологическим раком на дому в Дании - национальный обзор.

ЦЕЛЬ: Изучение масштабов и практики лечения на дому пациентов с гематологическими заболеваниями в Дании. МЕТОДЫ: Это общенациональное исследование проводилось во всех датских гематологовых департаментах (n = 9). На каждом сайте был получен онлайновый вопросник для сбора данных о типе терапии, применяемой в качестве лечения на дому, о конкретных методах лечения с подробной информацией о целевых группах населения, критериях для пациентов, ходе осуществления и практике клинического лечения.Результаты: Six В датских гематологических отделениях в качестве домашнего лечения предлагались такие виды т

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… BEAM: carmustine, Etopophos, cytarabine, melphalan; DA-EPOCH/EPOCH: rituximab, Etopophos, prednisolone, vincristine, cyclophosphamide, doxorubicin; DHAP: dexamethasone, high-dose arabine/cytarabine, cisplatin. … Conversely, one hospital did not have specific criteria for home-based treatment with rituximab, Etopophos, prednisolone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH/EPOCH) and carmustine, Etopophos, cytarabine, and melphalan (BEAM). …

Chinese Herbal Medicine Is Helpful for Survival Improvement in Patients With Multiple Myeloma in Taiwan: A Nationwide Retrospective Matched-Cohort Study.

Aim of the studyThe purpose of this study is to demonstrate that Chinese herbal medicine is beneficial for survival improvement in patients with multiple myeloma.Materials and methodsWe performed a 1:1 propensity score-matched cohort study to analyze patients with multiple myeloma diagnosed between January 1, 2002, and December 31, 2012, through the Taiwanese National Health Insurance Research Database. Patients who received Chinese herbal medicine therapy from the initial date of diagnosis of multiple myeloma to December 31, 2012, were included in the Chinese herbal medicine group. Patients w

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… Clin Lymphoma Myeloma . 2009 ; 9 : 278 - 288 . 19717377 10.3816/CLM.2009.n.056 PMC3910142 11 Ludwig H Hajek R Tóthová E , et al Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma . … N Engl J Med . 2003 ; 348 : 1875 - 1883 . 12736280 10.1056/NEJMoa022340 13 Palumbo A Bringhen S Caravita T , et al Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial . …

Subcutaneous bortezomib might be standard of care for patients with multiple myeloma: a systematic review and meta-analysis.

Background: Administration of subcutaneous (SC) bortezomib in patients with multiple myeloma (MM) has increased in recent years. Yet, it is unclear whether there is sufficient evidence to support the use of SC bortezomib as a standard of care. Methods: A systematic review of 4 randomized controlled trials and 8 retrospective trials comparing SC to intravenous (IV) bortezomib among 1,857 MM patients was performed. Embase, PubMed, Clinical Trials.gov, Cochrane Library and reference lists were searched for relevant studies from inception until August 2018. Outcomes of interest included 1-year ove

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… NDMM, newly diagnosed MM; RRMM, relapsed and/or refractory MM; PAd, bortezomib, doxorubicin, dexamethasone; VCD, cyclophosphamide, bortezomib, dexamethasone; VD, bortezomib, dexamethasone; VTD, bortezomib, dexamethasone, thalidomide; BCd, bortezomib, cyclophosphamide, dexamethasone; VMP, bortezomib, melphalan … Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma . Br J Haematol . 2009 ; 144 ( 6 ): 887 – 894 . doi: 10.1111/j.1365-2141.2008.07572.x 19183191 5. Attal M , Lauwers-Cances V , Hulin C , et al. …

FDA-Approved Drugs Containing Amide Functionality in the Last Five Years (2021-2025): Pharmaceutical Use, Trends and Synthetic Approaches.

The amide functional group remains a cornerstone of medicinal chemistry, serving as an indispensable scaffold in the design of modern therapeutics. This review presents an analysis of FDA-approved drugs (small molecules and peptides with MW ®), amides form the structural backbone of peptidomimetics, enabling high-affinity binding to a viral protease. In precision oncology, as seen with adagrasib (Krazati®), the amide acts as a critical, metabolically stable linker that positions a covalent warhead for selective inhibition of a mutant kinase. This analysis underscores that amide's unique combin

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… Melphalan Flufenamide Approved on 26 February 2021, melphalan flufenamide ( 27 , brand name Pepaxto ® , Figure 16 a) is a peptide-based drug designed to deliver the alkylating agent melphalan ( 28 ) preferentially into cancer cells with high aminopeptidase activity [ 77 ]. … Melphalan flufenamide is designed as a prodrug. Melphalan itself is polar and enters cells relatively inefficiently. By linking melphalan to a short peptide via an amide bond, the molecule becomes more lipophilic, allowing it to cross cell membranes much more easily [ 80 ]. …

Abstracts of the Cell Therapy Transplant Canada 2024 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2024 Annual Conference. The conference was held on 1-3 May 2024 in beautiful Victoria, British Columbia, at the Victoria Conference Centre, and attracted 293 in-person delegates and five virtual attendees. Several plenary sessions were held on topics such as gene therapy for hemoglobin disorders, optimizing donor selection, graft-versus-host disease (GvHD) strategies, collaborative care, survivorship, graft failure, and CAR-T therapy. Poster authors presented their work during a lively and e

Упорное использование опиоидов связано с более коротким выживанием миэломы.

Цель &quot; Превышение &quot; содержания опиоидов связана со значительным кризисом в области общественного здравоохранения, однако по-прежнему имеет решающее значение в качестве адъюнкт-процесса лечения во многих миеломах (ММ). Остаются вопросы о балансе между выгодами от продолжающегося использования опиоидов, особенно когда миэлома пациента находится в ремиссии. Этот ретроспективный обзор посвящен ассоциации хронического опиоида (COU) среди пациентов, преимущественно цветных. 174 В одном из городских медицинских центров были изучены пациенты, получившие аутологическую трансплантацию стволовы

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… Objectives Our primary endpoint was persistent chronic opioid use (COU) 6 months following ASCT as all melphalan-related toxicities other than fatigue have resolved by 6 months following ASCT. … Dimopoulos MA, Mateos MV, Richardson PG, Schlag R, Khuageva NK, Shpilberg O et al (2011) Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. …

T1 Mapping in Cardiovascular Magnetic Resonance-A Marker of Diffuse Myocardial Fibrosis in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Introduction: Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular diseases. In our study, we aimed to find subclinical changes in myocardial tissue after HSCT with the help of cardiovascular magnetic resonance (CMR) tissue imaging techniques. Methods: The data of 44 patients undergoing autologous and allogeneic HSCT in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics from October 2021 to February 2023 were analyzed. Bioethics approval for the prospective study was obtained (No BE-2-96). CMR was performed two times: before enr

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… Most drugs used for mobilization or conditioning, including cyclophosphamide, cytarabine, carmustine, and melphalan, are associated with significant toxicity. Additionally, effects attributed to dimethylsulfoxide used to preserve stem cells are also thought to contribute to cardiac events. … Conditioning was performed as follows: multiple myeloma patients with melphalan 200 mg/m 2 , lymphomas with BEAM (carmustine, etoposide, cytarabine, melphalan) protocol, primary central nervous system (PCNS) diffuse large B cell lymphoma—thiotepa and BCNU. …