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Прогресс в нескольких миеломах: ключевые обновления из ASH 2025 Встреча.

С расширением иммунных стратегий происходит стремительная трансформация терапевтического ландшафта с множественными миеломами (ММ). В этой редакционной статье резюмируются ключевые выдержки из ММ, представленные Американскому обществу гематологии (АШ) 2025 :: встреча на высшем уровне, в ходе которой особое внимание было уделено вопросу о том, каким образом подходы к адаптации к минимально остаточным заболеваниям (МВД) и иммунные платформы следующего поколения изменяют методы лечения на всех этапах заболевания ММ. В недавно диагностированном MM (NDMM) минимальное остаточное заболевание (MRD)-ад

Moving Beyond G-CSF Mobilization-Learning From a 15-Year Experience of Different Stem Cell Mobilization Regimens in Multiple Myeloma.

BackgroundStem-cell mobilization in multiple myeloma is usually done with G-CSF with or without Cyclophosphamide (Cy) based chemotherapy/Plerixafor. Pre-clinical data suggest the role of proteasome inhibitors in mobilization. We previously reported that Bortezomib (Bort) when added to a Cy-based regimen had a better stem-cell yield. Consequent to favorable results with Bort + Cy-G-CSF, we used Bortezomib with G-CSF too. Hence, four different mobilization regimens were used-Bort + G-CSF (Group-1); G-CSF + Plerixafor (Group-2); Bort - Cy-G-CSF (Group-3); Cy + G-CSF (Group-4). We report here our

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… Additionally, even daratumumab has a negative impact on stem‐cell collection [ 8 ] with lesser yield and more need for plerixafor (PEF), in daratumumab‐based quadruplets versus triplets [ 9 ]. … Newer drugs like Daratumumab and Motixafortide have been approved in myeloma as quadruplet therapy in newly diagnosed patients [ 6 ], and for stem‐cell mobilization [ 36 ], respectively. …

Доказательства для мониторинга динамики минимальных остаточных заболеваний с целью руководства клинической практикой у пациентов с множественной миеломой.

Множественная миелома (ММ) — разнородный рак, который остается неизлечимым. После лечения наличие остаточных клоновых клеток миэломы или минимального остаточного заболевания (МВД) приводит к рецидиву (воскрещению) опухоли и неисправности лечения (рекреторное заболевание). Твердые клинические данные свидетельствуют о том, что MRD является суррогатным показателем выживания у пациентов с MM и имеет важное прогнозируемое значение для лечения заболеваний. Статус MRD представляет собой динамические изменения, а продольные изменения в статусе MRD имеют различные клинические последствия. Например, уст

Review of patient-reported outcomes in multiple myeloma registrational trials: highlighting areas for improvement.

Over the past 13 years, there have been advances in characterizing the patient experience in oncology trials, primarily using patient-reported outcomes (PROs). This review aims to provide details on the PRO measures and analyses used in multiple myeloma (MM) registrational trials. We identified registrational trials supporting MM indications from 2007 to 2020 from FDA databases. Trial protocols, statistical analysis plans, and clinical study reports were reviewed for PRO measures used, collection methods, statistical analyses, baseline and instrument completion definitions, and thresholds for

Emerging Real-World Treatment Patterns and Clinical Outcomes of Multiple Myeloma in Argentina and Brazil: Insights from the TOTEMM Study in the Private Healthcare Sector.

As treatments for multiple myeloma (MM) evolve, there is a need for real-world insights into treatment patterns and outcomes. The treatment practices and clinical outcomes in patients with MM (TOTEMM) was a database study (2018-2024) of newly diagnosed transplant-ineligible patients with MM in Argentina (TOTEMM-A) and Brazil (TOTEMM-B) in a private healthcare setting. In TOTEMM-A (n = 72) and TOTEMM-B (n = 892), 37 and 92 different drug regimens were reported, respectively. In each country, treatment duration reduced across lines of therapy (LOT) (TOTEMM-A: range, 6.2-3.4 months; TOTEMM-B: ran

Оптимизация многочисленных методов лечения миэломы в условиях ограниченности ресурсов: нынешние перспективы и проблемы.

Множественная миелома (ММ) представляет собой серьезную глобальную проблему в области здравоохранения, и за последние десятилетия уровень ее распространенности и смертности неуклонно возрастал. В настоящем обзоре содержится критический анализ нынешнего положения дел в области управления ММ с особым упором на ограниченные ресурсами условия, в которых наиболее заметны различия в диагностических возможностях и вариантах лечения. Комплексный поиск литературы был проведен с использованием многочисленных баз данных, включая рецензированные статьи, клинические руководящие принципы и резюме конференци

Steps towards a Multiple Myeloma Cure?

Multiple myeloma survival has increased in last 20 years because of new treatments, better clinical management due to novel diagnostic tools such as imaging, and better understanding of the disease, biologically and genetically. Novel drugs have been introduced that act with different therapeutic mechanisms, but so have novel therapeutic strategies such as consolidation and maintenance after autologous stem cell transplant. Imaging (such as PET-CT and MRI) has been applied at diagnosis and after therapy for minimal residual disease monitoring. Multiparametric flow and molecular NGS may detect,

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… Triplet and quadruplet combinations have demonstrated significative benefits when used in HR patients in many clinical trials [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. … Novel triplets and quadruplets are being tested, as is the monoclonal anti-CD38 antibody associated with bortezomib lenalidomide (Dara-VRD, GRIFFIN study, with 51% MRD negativity reported) [ 60 ]. …

The Anti-CD38 Antibody Therapy in Multiple Myeloma.

Multiple myeloma (MM) is the second-most common hematologic malignancy after diffuse large B-cell lymphoma. Despite the improvement in response and survival rates following the introduction of novel therapies, only a few patients are cured, and the majority of MM patients experience several relapses and receive multiple lines of treatment. Currently, bortezomib and lenalidomide are the core component of treatment both at the time of diagnosis and at the relapse as well as the new proteasome inhibitors (PIs), such as carfilzomib and ixazomib, and the next-generation immunomodulatory drug, pomal

Clarithromycin, ixazomib, pomalidomide, dexamethasone for relapsed/refractory myeloma: survival and correlative analysis.

Clarithromycin is a macrolide antibiotic with anti-multiple myeloma (MM) activity when combined with dexamethasone and immunomodulatory agents. This phase 1/2 study of clarithromycin, ixazomib, pomalidomide, and dexamethasone (ClIPd) assessed tolerability and efficacy in relapsed/refractory MM. The primary end points were the maximal tolerated and recommended phase 2 dose. Key secondary end points were the overall response rate (ORR) (≥partial response), disease control rate (DCR) (≥stable disease), progression-free survival (PFS), and overall survival (OS). All 4 medications were given at ful

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… therapy developed before monoclonal antibodies led to deeper responses and PFS benefits. 6 Monoclonal antibody–containing quadruplets are now being moved into earlier lines of therapy. … In conclusion, ClIPd is an all-oral quadruplet regimen that is relatively well tolerated and offers convenient dosing with relatively high rates and durable responses and is feasible for patients in whom parenteral therapy is not feasible or preferred. …

Monoclonal Antibodies: Leading Actors in the Relapsed/Refractory Multiple Myeloma Treatment.

Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and

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… This quadruplet induced an ORR of 61% and a median PFS of 9.8 months. In patients with one prior line of therapy, ORR was 74% and median PFS was not reached. … Other quadruplets including elotuzumab are under investigation in the setting of RRMM. …

Belantamab mafodotin, carfilzomib, lenalidomide и дексаметазон для рецидива или рефракта множественной миеломы.

Резюме Belantamab mafodotin (Belamaf), антитела-наркотики, направленные против антигена ячеек B-клеток, продемонстрировало активность одного агента в повторной/охлажденной миеломе (RRMM), но связано с окулярной токсичностью. Это фазы 1/2 в ходе исследования была проведена оценка безопасности и предварительной эффективности использования беналафа 8 Недели в сочетании с карфилзомидом, линалидомидом и дексаметасоном (KRd-b) у пациентов с RRMM. Пациенты, имеющие право на получение помощи, по крайней мере, 1 :: предыдущая терапия и не продвинулась по полной дозе леналидомида. На стадии " доза-

Outcomes and treatment patterns in primary and secondary plasma cell leukemia: insights from a large US cohort study.

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder with a short survival duration despite the use of novel therapeutics. PCL remains an understudied disease for which there is no current standard of care treatment. Knowledge on optimal novel drug sequencing, including the role and timing of hematopoietic stem cell transplant as primary and salvage therapy is needed. We conducted a large retrospective analysis of 153 PCL patients, using the new definition of ≥5% circulating plasma cells, including clinical features and treatment outcomes across seven academic centers in th

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… Daratumumab-containing quadruplets were infrequently used in both groups (3.6% in pPCL vs . 3.7% in sPCL; P =0.003). Clinical outcomes showed that more pPCL patients achieved a complete response (CR) or better (62.5%, 25/40) compared to sPCL patients (41.7%, 10/24) ( P =0.126). … Improved survival of patients with primary plasma cell leukemia with VRd or daratumumab-based quadruplets: a multicenter study by the Greek myeloma study group. Am J Hematol. 2023;98(5):730-738. 28. Katodritou E, Verrou E, Gastari V, Hadjiaggelidou C, Terpos E, Zervas K. …

The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma.

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a signi

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… Moreover, given the mechanism of action and safety profile of MoAbs, the shift from triplets to quadruplets has not resulted in a worsening of patients’ quality of life [ 2 , 3 ]. … Anti-CD38 MoAb-based quadruplets are likely to become the new standard of care combined with ASCT in NDTEMM patients. Additional studies are needed to identify the best treatment strategy for HR patients. The clinical results of Elo in the setting of NDTEMM appear still immature. …

Клинические характеристики, лабораторные меры и качество жизни как предвестники соблюдения лекарств в множестве миеломы.

Соблюдение лекарств в миеломе (ММ) является одним из ключевых факторов, определяющих результаты лечения, однако его взаимосвязь с качеством жизни, о котором сообщают пациенты, по-прежнему недостаточно изучена. Мы провели многоцентральное перекрестное исследование по всему спектру five Больницы на Западном берегу2018–2025), зачисление 250 Взрослые с MM на активном лечении. При поступлении в школу пациенты закончили ЭОРТК QLQ-MY20 для оценки КОЛ для конкретных заболеваний, и one Месяц спустя была проведена оценка участия в программе с использованием Moricy Mediction. Scale-4 (В тыс.MMAS-4). Боль

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… Contemporary international guidelines from NCCN, EHA–ESMO, and IMWG-aligned expert reviews recommend lenalidomide–bortezomib–dexamethasone (VRd) and daratumumab-based quadruplets as preferred first-line options in newly diagnosed MM 7 , 11 , 12 . … Implications in the Era of CD38-based quadruplet regimens In recent years, frontline management of multiple myeloma has increasingly adopted CD38 antibody–based quadruplet regimens that combine a proteasome inhibitor, an immunomodulatory agent, dexamethasone, and an anti-CD38 monoclonal antibody. …

In search of the optimal proteosome inhibitor. How, when and for whom?

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… Table 1 summarizes the information regarding selected carfilzomib- and bortezomib-containing doublets, triplets and quadruplets in RRMM/NDMM, and in transplant-eligible and –ineligible patients. … Exclusion criteria for ENDURANCE were high-risk MM patients, 4 postulated to profit better from antibody-based quadruplets. Although the rate of very good partial response or better in ENDURANCE was significantly higher with KRd than with VRd, this did not translate into better 3-year PFS and OS. …

Модификация РНК не позволяет расширить кодон-антикодонное взаимодействие облегчить +1 Смена рамы.

Закон о внесении изменений после записи в РНК путем стабилизации функционального соответствия РНК. Хотя их роль в декодировании генератора РНК (mRNA) хорошо установлена, менее ясно, как перенос изменений РНК (tRNA) за пределы антикодона способствует стабильности tRNA и точному синтезу белка. Отсутствие таких изменений приводит к ошибкам в переводе, в том числе к смене mRNA. Интегрировав передачу энергии одним молекулярного флуоресцентного резонанса и криогенную электронную микроскопию, мы продемонстрируем, что N1-methylguanosine (м1G) модификация в положении 37 Эшеричиа коли tRNAProL необходим

Hematologic response assessment in monoclonal gammopathy of renal significance: critical appraisal of current criteria.

INTRODUCTION: Current recommendations for hematologic response (HemR) assessment in monoclonal gammopathies of renal significance (MGRS) are based on the monoclonal immunoglobulin (MIg) component responsible for renal damage. Light-chain (LC) amyloidosis criteria are recommended when renal lesions are due to LC, whereas multiple myeloma (MM) criteria are proposed when due to an intact monoclonal immunoglobulin. However, the nephrotoxic MIg is frequently not measurable either by the International Myeloma Working Group (IMWG) or the International Society of Amyloidosis (ISA) criteria. METHODS: I

A Clinical Perspective on Plasma Cell Leukemia: A Single-Center Experience.

Circulating plasma cells (CPCs) are detected in most multiple myeloma (MM) patients, both at diagnosis and on relapse. A small subset, plasma cell leukemia (PCL), represents a different biology and has a poor prognosis. In this retrospective analysis, we evaluated patients with primary (pPCL, n = 35) or secondary (sPCL, n = 49), with ≥5% CPCs and a smaller subset with lower CPCs of 1-4% (n = 20). The median age was 61 years; 45% were men and 54% were Black. High-risk cytogenetics were found in 87% and extramedullary disease in 47%. For the entire cohort, 75% received a proteasome inhibitor, 70

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… The treatment regimens were analyzed by drug class and not specific regimens (triplets, quadruplets), and they were subject to clinician’s bias and the nature of relapse. … Improved survival of patients with primary plasma cell leukemia with VRd or daratumumab-based quadruplets: A multicenter study by the Greek myeloma study group. Am. J. Hematol. 2023;98:730–738. doi: 10.1002/ajh.26891. 31. …

Функциональное заболевание с повышенным риском связано с плохими результатами лечения нескольких миеломы с помощью клеточной терапии CAR.

В то время как CART продемонстрировала высокую эффективность на ранней линии терапии [1, 2] для функционально высокорисковых множественных миэлом (FHRMM), результаты с их использованием в более поздних строках (3+) по болезням, связанным с ПФЗ, остаются неизвестными. Мы описываем одноцентричный опыт пациентов FHRMM (pts), определяемый как пациенты с прогрессирующими заболеваниями (POD) < 24 месяцев передней терапии, прохождения T-клеточной терапии CAR. Из числа 208 ПТ, обработанные CART, 117 (В тыс.56%) имели болезнь ФПЧ и получили медианную долю 5 - предыдущая терапия (СОТ). У ПШФ были более

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… The baseline patient and disease characteristics were well balanced between the two groups except that functionally high-risk patients had higher rates of EMD (39% versus (vs) 24%, p = 0.024), more frequent use of quadruplets as frontline therapy (15% vs 6%, p = 0.047), higher incidence of disease progression … Similarly, a real-world analysis of 312 patients who received quadruplet induction therapy and ASCT with disease progression within 36 months of frontline therapy had reduced 2PFS (HR 2.92, 95% C.I. 1.27–2,67, P = 0.012) and OS (HR 6.66, 95% C.I. 1.56–28.47, P = 0.011). …

An objective assessment in newly diagnosed multiple myeloma to avoid treatment complications and strengthen therapy adherence.

In heterogeneous multiple myeloma (MM) patients treatment decisions are challenging. The hypothesis was that adaptation of treatment intensity (dose reduction [DR] vs. none) according to an objective risk score (revised-myeloma comorbidity index [R-MCI]) rather than physician judgement alone may improve therapy efficacy and avoid toxicities. We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, after having received induction protocols based on physicians' judgement. DR, serious adverse events (SAE), response, progression-free surv

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… proteasome inhibitors (PI), immunomodulatory drugs (IMiDs) and antibodies (Ab)/immunotherapies into induction and relapse protocols, response rates, progression-free survival (PFS) and overall survival (OS) have improved impressively. 2 Standard treatment in newly diagnosed MM (NDMM) includes triplets or quadruplets … to other hematological malignancies, seems relevant to achieve favorable treatment results, less DR, SAE, as few unscheduled re-hospitalizations and preserved QoL. 7 , 12 , 42 , 48 , 49 The latter demonstrated itself to be possible even after intensive regimens, after allogeneic transplantation or quadruplet …