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Real-world incidence of severe infections in multiple myeloma patients receiving bispecific antibodies: a meta-analysis.

Bispecific antibodies (BiTEs) have transformed the therapeutic landscape of relapsed/refractory multiple myeloma (RRMM), offering deep and durable responses even in heavily pretreated patients. However, their use carries substantial infectious risk due to immunosuppression, particularly hypogammaglobulinemia, induced by T-cell-redirecting therapy. To define the real-world incidence of grade 3–4 infections, we conducted a systematic review and meta-analysis of retrospective studies including RRMM patients treated with BiTEs currently approved for clinical use. Ten studies encompassing 1,373 pat…

Кардиотоксичность, вызванная множественными миэломатерапиями: механистическая конвергенция между протеиновыми ингибиторами, CAR-T и биконкретными антителами.

Сердечно-сосудистая токсичность стала важным препятствием на пути реализации полного клинического потенциала современной терапии для множественных миэломы (ММ), включая протеазонные ингибиторы (ИП), химерика антигенного рецептора Т-клеток (CAR-T) и CD3-engaging Биотипные антитела. Здесь мы обсуждаем эпидемиологию, лежащую в основе механистических путей, и новые стратегии предотвращения кардиотоксичности, вызванной терапией, в MM. На основе данных, полученных в ходе исследований по изучению мультиомики, доклинических моделей и данных наблюдений в реальном мире, мы синтезируем вклад митохондриал

Совпадение в аннотации оригинала
Cardiovascular toxicity has emerged as an important obstacle to realizing the complete clinical potential of contemporary therapies for multiple myeloma (MM), including proteasome inhibitors (PIs), chimeric antigen receptor T-cell (CAR-T) therapies, and CD3-engaging bispecific antibodies. Here, we discuss the epidemiology, underlying mechanistic pathways, an…

Determinants of clinical trial participation in multiple myeloma: A population-based cohort study from British Columbia.

BACKGROUND: Clinical trials play a central role in advancing therapy for multiple myeloma (MM), yet participation remains limited and may be influenced by clinical, geographic, and socioeconomic factors. The extent to which these factors shape trial participation and whether participation is independently associated with overall survival (OS) in real-world MM populations remain uncertain, particularly within centralized healthcare systems. METHODS: We conducted a retrospective cohort study of adult patients with MM treated at two tertiary referral centers in British Columbia between 2000 and …

Arlocabtagene autoleucel: a GPRC5D-targeted CAR T-cell therapy for heavily pretreated relapsed/refractory multiple myeloma.

Patients with relapsed/refractory multiple myeloma (RRMM) have limited treatment options. Arlocabtagene autoleucel (arlo-cel; BMS-986393) is an autologous chimeric antigen receptor (CAR) T-cell therapy targeting G protein-coupled receptor class C group 5 member D (GPRC5D). This phase 1, dose-escalation/expansion study enrolled adult patients with RRMM and ≥3 previous antimyeloma treatment regimens, including an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody. Patients (N = 84) had a median of 5 prior regimens, and 49% had previously received B-cell maturation antigen-target…

Product-intrinsic NF-κB-driven transcriptional programs connote durability of CAR-T response in multiple myeloma.

Idecabtagene vicleucel (ide-cel) induces deep responses in relapsed/refractory multiple myeloma, yet more than half of patients relapse within 1 year. The intrinsic features of chimeric antigen receptor T-cell (CAR-T) products that distinguish durable from nondurable responders are poorly defined, particularly at single-cell resolution, and defining drivers of durable response is critical to guide patient counseling and to inform strategies for optimizing CAR-T manufacturing and efficacy. To address this need, 40 ide-cel infusion products (184 398 cells) were profiled using single-cell RNA seq…

Pomalidomide significantly enhances the antitumor immune efficacy of dendritic cell-derived exosomes from multiple myeloma patients.

BACKGROUND: To explore the effect and mechanism of pomalidomide on the immune activity of dendritic cell-derived exosomes (DEXs) from patients with multiple myeloma (MM). METHODS: MoDCs were induced from monocytes obtained from patients with MM and HDs with or without pomalidomide treatment. DEXs were then isolated from culture supernatants via ultracentrifugation and characterized by TEM and NTA. Surface markers (CD63, CD81, CD80, CD86, and HLA-DR) were analyzed using nanoflow cytometry. Functional assays included coculturing DEXs with autologous PBMCs to activate T cells, followed by sortin…

Linvoseltamab versus elranatamab for triple-class exposed relapsed or refractory multiple myeloma: an indirect treatment comparison.

We conducted unanchored matching-adjusted indirect comparisons (MAICs) of the BCMA × CD3 bispecific antibodies, linvoseltamab and elranatamab, in triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). Patient-level data from BCMA-targeted therapy-naïve patients in LINKER-MM1 (linvoseltamab; NCT03761108; n = 107; data cutoff (DCO): 07/2024; median follow-up: 21.3 months) were matched to MagnetisMM-3 Cohort A (elranatamab; NCT04649359; N = 123; DCO: 09/2024; median follow-up: 33.9 months). Linvoseltamab demonstrated significantly (p < 0.05) higher overall response (71.5% vs. 61.…

Site-Specific Profiling of Monoclonal IgG N-Glycosylation Reveals Dynamic Sialylation Changes Associated with Multiple Myeloma.

The glycosylation of monoclonal immunoglobulins (M-proteins) is implicated in the pathogenesis of multiple myeloma (MM), but a comprehensive, site-specific glycoproteomic characterization has been lacking. Here, we established an integrated workflow that couples serum protein electrophoresis with ZenoTOF mass spectrometry for the in-depth quantitative profiling of intact N-glycopeptides from purified serum M-proteins. This method was applied to a cohort including healthy controls (HCs) (n = 26), patients with IgG-MGUS (monoclonal gammopathy of undetermined significance) (n = 23), and IgG-MM pa…

Множественная миелома: многострановое исследование по смешанным методам, касающимся восприятия заболеваний и предпочтений лечения пациентов.

AIMS: Уяснить представления о заболеваниях и предпочтениях лечения пациентов с высокой степенью риска, страдающих множественным миэломой (HR-SMM) или множественной миэломой (MM), которая недавно прошла через HR-SMM, и оценить минимальный уровень выживаемости (мин-PFS), необходимый для того, чтобы принять лечение. МЕТОДЫ: Опрошенное исследование по смешанным методам 50 пациентов (HR-SMM и MM) 1::1) от США, Франции, Италии и Испании. Качественные полуструктурированные собеседования были посвящены изучению симптомов, качества жизни, а также осведомленности и ожиданий в отношении лечения SMM. Коли

Совпадение в аннотации оригинала
AIMS: To understand disease perceptions and treatment preferences of patients with high-risk smoldering multiple myeloma (HR-SMM) or multiple myeloma (MM) that recently progressed from HR-SMM, and to estimate the minimum progression-free survival (min-PFS) required to accept the treatment burden. METHODS: This mixed-methods study interviewed 50 patients (HR…

Промежуточный анализ в клинических испытаниях: предостережение от преждевременных выводов - многократное тематическое исследование по миэломе S0777.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Временный контроль за эффективностью и бесполезностью обеспечивает критически важные границы принятия решений о досрочном прекращении случайных клинических испытаний. Такой анализ может ускорить доступ к эффективным методам лечения и ограничить воздействие неэффективных методов лечения, однако его следует взвешивать с учетом преждевременного закрытия, которое может скрыть реальную пользу от лечения. Мы обсуждаем эти соображения и представляем тематическое исследование, в котором подчеркивается важность выполнения хорошо разработанного промежуточного аналитического плана.

Совпадение в аннотации оригинала
BACKGROUND: Interim monitoring for efficacy and futility provides critical decision-making boundaries on early termination of randomized cli … d phase III study of bortezomib, lenalidomide, and dexamethasone (VRd) versus Rd in newly diagnosed multiple myeloma that incorporated two pre-planned interim analyses. At both interim analyses, while the futility stopping boundaries were not crossed, the accumulating data suggested a limited or diminishing benefit in progression-free survival (PFS). In contrast, …

Японский подгруппный анализ процесса по делу AQUILA: Daratumumumab vs активный мониторинг в нескольких миеломах высокого риска.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: На глобальном этапе 3 испытания AQUILA монотерапия &lt; &lt; Даратумумаб &gt; &gt; была связана с значительно более низким риском перехода к активной миеломе или смерти, чем активный мониторинг у пациентов с множественными миеломами высокого риска без неожиданных опасений по поводу безопасности (NCT03301220). Вот, мы доложим о подгруппе анализа японских пациентов с испытания. Из 28 японских пациентов 15 и 13 пациентов получили, соответственно, Daratumumumab и активный контроль. РЕЗУЛЬТАТЫ: При среднем промежутке времени в 60,9 месяца медиана выживаемости без прогрессиров

Совпадение в аннотации оригинала
BACKGROUND: In the global phase 3 AQUILA trial, daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death than active monitoring in patients with high-risk smoldering multiple myeloma without unexpected safety concerns (NCT03301220). METHODS: Here, we report a subgroup analysis of Japanese patie…

Elevated D-dimer levels in high-risk multiple myeloma patients: a systematic review and meta-analysis.

BACKGROUND: Patients with multiple myeloma (MM) exhibit elevated thrombotic risk and variable disease outcomes. D-dimer, a fibrin degradation product, may serve as a biomarker reflecting both hypercoagulability and disease severity. This systematic review and meta-analysis compared D-dimer levels between MM patient subgroups defined by either poor prognostic features (e.g., advanced ISS stage) or thrombotic events and reference groups, with detailed discussion of how D-dimer integration reshapes routine thromboprophylaxis strategies and upgrades classic prognostic staging tools (ISS, R-ISS, IM…

Soluble B-cell maturation antigen levels for disease monitoring in oligosecretory and nonsecretory relapsed multiple myeloma.

Soluble B-cell maturation antigen (sBCMA) is elevated on multiple myeloma (MM) cells. We investigated whether sBCMA levels correlated with other myeloma tumor volume indicators and its utility in monitoring oligosecretory/nonsecretory (O-S/Non-S) MM. In 115 patients with newly diagnosed MM, sBCMA was compared with M-protein levels, bone marrow plasma cells (BMPCs), circulating tumor cells (CTCs), and total diffusion volume (tDV; estimated by whole-body diffusion-weighted magnetic resonance imaging) at diagnosis. sBCMA levels increased significantly with International Staging System stage, chro…

Early Identification of the Non-Transplanted Functional High-Risk Multiple Myeloma: Insights from a Predictive Nomogram.

Background: Patients with multiple myeloma (MM) who have a suboptimal response to induction therapy or early relapse are classified as functional high-risk (FHR) patients and have been shown to have a dismal prognosis. The aim of this study was to establish a predictive nomogram for patients with non-transplanted FHR MM. Materials and Methods: The group comprised 215 patients in our center between 1 January 2006 and 1 March 2024. To identify independent risk factors, univariate and multivariate logistic regression analyses were performed, and a nomogram was constructed to predict non-transplan…

Real-World Evidence Evaluating Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma: A Systematic Literature Review.

Background: Teclistamab (TEC) is the first B-cell maturation antigen-directed bispecific antibody approved in 2022 by the European Medicines Agency and Food and Drug Administration for triple-class exposed relapsed/refractory multiple myeloma (RRMM). Objectives: As TEC is increasingly used in real-world (RW) settings, this study seeks to gather existing RW evidence on effectiveness, safety, healthcare resource utilization, and clinical practices associated with TEC. Methods: A systematic literature review was performed to identify RW observational studies of TEC-treated adults with RRMM from 2…

Structure-guided engineering of CCL27 enhances natural ligand CAR T-cells against CCR10 for multiple myeloma.

Despite the success of BCMA CAR-Ts, many multiple myeloma patients relapse and require additional therapeutic options. Our group previously identified the chemokine receptor CCR10 as a potential alternate target to address this need. Here, we validated CCR10 expression on primary myeloma tumors and sought to develop CAR T-cells against CCR10, utilizing its natural ligand CCL27 as a CAR binding element. However, CARs based on the native CCL27 sequence were ineffective. We thus utilized computational modeling and structure-guided engineering to inform rational mutations along the CCL27-CCR10 int…

Minimal residual disease measurement in blood by mass spectrometry identifies long-term responders in multiple myeloma.

Modern multiple myeloma treatment enables deep and sustained responses, necessitating assessment of minimal residual disease (MRD) in the bone marrow to refine response categorization. Recently, mass spectrometry (MS)-based methods have emerged as highly sensitive tools for measuring MRD in the peripheral blood. However, the role specific MS techniques play in response categorization has yet to be established. We pooled data from 97 patients treated in 3 prospective phase 2 trials evaluating carfilzomib-based triplets and quadruplets, with or without autologous stem cell transplantation. MRD w…