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Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma.

BackgroundIn a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma.MethodsIn this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab-daratumumab or daratumumab combined with dexamethasone plus the investigator's…

Managing Novel CAR T-Cell Toxicities in Multiple Myeloma.

B-cell maturation antigen (BCMA) targeted chimeric antigen receptor T-cell (CAR-T) cell therapy has proven highly efficacious for relapsed multiple myeloma, inducing deep and durable remissions. Recent reporting has bolstered significant enthusiasm, describing upwards of one-third of patients in continued remission, 5 years following BCMA CAR-T without receiving any subsequent therapy, suggesting the possibility that this treatment may offer the hope of a cure. There are many well-characterized side effects from CAR-T, and mitigation strategies have been established to make this therapy safe. …

Ferroptosis targeting: a novel therapeutic armamentarium in multiple myeloma.

Multiple myeloma (MM), a hematological malignancy characterized by abnormal plasma cell proliferation, remains incurable because of its pervasive resistance to therapy. Consequently, promising therapeutic strategies are urgently needed to improve treatment responses and long-term outcomes in patients with MM. Emerging preclinical evidence indicates that ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation and iron dysregulation, may suppress the progression of MM. Several compounds have demonstrated efficacy in eliminating MM cells through ferroptosis induct…

Haploidentical Allogeneic Cell Transplantation in Relapsed/Refractory Multiple Myeloma.

PURPOSE: Although emerging therapies for multiple myeloma (MM) have improved treatment options, long-term disease control in relapsed/refractory (r/r) MM remains a challenge. While the effect of natural killer cell alloreactivity in haploidentical allogeneic hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis is considered a standard treatment option for several hematologic neoplasms, its use in MM is controversial. In this retrospective analysis, we evaluated a small cohort of consecutive patients with MM w…

Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.

Multiple myeloma (MM) is a plasma cell malignancy that originates in the bone marrow (BM) and is characterized by the clonal expansion of Bcell-derived plasma cells producing abnormal monoclonal immunoglobulins. Despite significant therapeutic advances that have improved patient outcomes, drug resistance remains a major obstacle to effective disease management. Genetic and epigenetic heterogeneity are key features of MM that drive disease onset, progression, and therapeutic resistance. Both early and advanced stages of MM exhibit global and locus specific DNA methylation abnormalities that sil…

Multifactorial Torsades de Pointes in a Multiple Myeloma Patient.

BACKGROUND: In patients with cancer, arrhythmic risk is compounded by concomitant QT interval-prolonging supportive medications, electrolyte derangements, cardiotoxic antineoplastic agents, thromboembolism, and underlying cardiac disease. CASE SUMMARY: We present a 61-year-old woman with IgG lambda multiple myeloma who, after 17 months of maintenance therapy with lenalidomide and bortezomib, experienced an out-of-hospital ventricular fibrillation arrest followed by in-hospital torsades de pointes (TdP). DISCUSSION: This case reinforces that TdP in patients with cancer is multifactorial and t…

Bone-modifying therapy in multiple myeloma: a comprehensive review.

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the…

Multiple myeloma risk linked to DNA damage response genes.

BACKGROUND: DNA damage response genes (DDRG), implicated in several cancers as both predisposing risk factors as well as biomarkers for aggressiveness, have not been fully explored in multiple myeloma (MM). METHODS: Herein, we analyzed disease associations of pathogenic variations in nine putative candidate genes using 3 446 MM cases and 323 233 cancer-free controls. RESULTS: Increased MM risk was found to be associated with inherited rare pathogenic mutations in TP53, ATM, CHEK2, KDM1A, and ARID1A, with an enrichment of these variants among individuals with early onset or family history of …

Risk stratification and early intervention in smoldering multiple myeloma.

Smoldering multiple myeloma (SMM) is a biologically diverse precursor to multiple myeloma (MM), characterized by varying risks of progression. Several validated risk stratification models help identify patients at the highest risk, who may benefit from early treatment at the precursor stage. Current guidelines recommend treatment with lenalidomide, with or without dexamethasone, or participation in clinical trials for patients with high-risk SMM. Recent data also support using daratumumab monotherapy, which has been shown to significantly delay progression to MM. However, uncertainties remain …

Diagnosis, risk stratification and management of smouldering multiple myeloma.

New therapies have markedly improved survival outcomes for patients with multiple myeloma (MM). However, the onset of active disease, as defined by the 2014 International Myeloma Working Group SLiM-CRAB criteria, is often linked to substantial and irreversible morbidity. MM always develops from an asymptomatic precursor state called smouldering multiple myeloma (SMM). The clinical trajectory of SMM varies considerably; low-risk SMM often has an indolent course, similar to monoclonal gammopathy of undetermined significance, whereas nearly half of the subset of patients with high-risk SMM have p…

Early intervention for high-risk smoldering multiple myeloma (SMM).

RATIONALE: Smoldering multiple myeloma (SMM) represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma. Early identification and intervention for people with high-risk SMM may prevent or delay progression to symptomatic disease. Current evidence on the optimal timing and choice of intervention remains controversial, necessitating a systematic evaluation. OBJECTIVES: To evaluate the benefits and harms of different early interventions compared to observation alone or placebo in people with high-risk smoldering multiple myeloma…

Ингибиция Calpain-2 смягчает гиперкальцемию, вызванную несколькими миеломами.

Множественная миелома (ММ) — злокачественное гематологическое расстройство, характеризующееся неопластическим распространением плазменных клеток. Гиперкальцемия является распространенным осложнением в MM и часто считается вторичным последствием развития болезни. Когда уровень кальция сильно повышен, он может привести к коме у больных. Однако остается неясным, играет ли гиперкальцемия непосредственную роль в развитии ММ. Здесь мы обнаружили, что высокие концентрации кальция способствуют распространению клеток MM и связаны с кальпаином-2 (CAPN2). Мы также отметили, что выражение CAPN2 значительн…

CD70-targeted platform for diagnosing and treating multiple myeloma.

BackgroundCD70, overexpressed in multiple myeloma (MM), is a promising target for theranostics. This study developed a CD70-targeted theranostic pair: the immuno-positron emission tomography tracer [89Zr]Zr-DFO-ABDB6 and the therapeutic agent [177Lu]Lu-DOTA-ABDB6, aiming to combine imaging and radiotherapy for MM.MethodsCD70 expression was confirmed in patients with MM samples (positivity rate, 66.7%) and RPMI-8226 xenografts. The nanobody derivative ABDB6 was conjugated to DFO or DOTA and radiolabeled with 89Zr or 177Lu. Pharmacokinetics, biodistribution, and toxicity were evaluated in NCG an…

MRD в множестве миеломы: переход от "минимального" к "измеримого".

Оценка минимальных остаточных заболеваний (МРД) является важным прогнозным фактором гематологовых магнестов, включая множественные миеломы (ММ). Традиционно определяемые как раковые клетки, не обнаруживаемые обычной морфологией, MRD сейчас более уместно называют измеримыми остаточными заболеваниями, отражающими его количественный и клинический характер. Прогресс, достигнутый в области цитометрии потока следующего поколения и последовательности следующего поколения, позволил обнаружить болезнь при чувствительности до 10-6 и даже 10-7, переосмысливая концепцию полного реагирования. Тем не менее

Совпадение в аннотации оригинала
The assessment of minimal residual disease (MRD) is an important prognostic factor in hematologic malignancies, including multiple myeloma (MM). Historically defined as cancer cells undetectable by conventional morphology, MRD is now more appropriately termed measurable residual disease, reflecting its quantitative and clinically actionable nature. Advances …

Множественная миелома, имитирующая лимфопролиферативное заболевание на мультимодальной съемке.

77-летний самец с моноклональной гаммопатией недоопределенного значения, поражаемой множеством громоздких сверхфункциональных мягких масс на фотографических тестах, имитируя радиологические особенности лимфомы. В конечном итоге был установлен диагноз многофункциональной многоразовой миеломы, что подчеркивает необходимость комплексной клинической и диагностической корреляции для обеспечения надлежащего управления.

Совпадение в аннотации оригинала
A 77-year-old male with monoclonal gammopathy of undertermined significance presented with multiple bulky extraosseous soft-tissue masses on imaging tests, mimicking radiological features of lymphoma. Ultimately, a diagnosis of multifocal extraosseous multiple myeloma was established, highlighting the need for comprehensive clinical and diagnostic correlatio…

Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma.

BackgroundCurrent treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression. The appropriate duration of maintenance therapy with lenalidomide has been unclear.MethodsIn this phase 3 trial, we enrolled patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation. After induction treatment with a proteasome inhibitor-lenalidomide combination, patients were randomly assigned to receive indefinite-duration (continuous) lenalidomide or fixed-duration lenalidomide (for…

Acute pancreatitis induced by Daratumumab during multiple myeloma maintenance.

IntroductionAcute pancreatitis is a potential but rare adverse drug reaction. We report a delayed-onset case induced by daratumumab during multiple myeloma maintenance.Case ReportA 60-year-old non-smoking male under maintenance therapy with daratumumab, lenalidomide, and dexamethasone presented with sudden-onset acute abdominal pain and severe enzymatic elevation (amylase >40x ULN). Biliary and metabolic etiologies, as well as lenalidomide triggers, were thoroughly ruled out.Management & OutcomeDiscontinuation of daratumumab and conservative management led to complete clinical and biochemical …

Practical insights into bispecific antibody therapy in multiple myeloma.

INTRODUCTION: The rise of recent novel therapies teclistamab, elranatamab, and talquetamab for the treatment of relapsed/refractory multiple myeloma (RRMM) is a rapidly evolving area with significant clinical implications that require exploration and evaluation. AREAS COVERED: The current review highlights the clinical trial data, safety endpoints, and practical administration considerations for the bispecific therapies currently used in multiple myeloma. This article reviewed the efficacy and safety results between the three different bispecifics, and the differences in dosing and monitoring…

[Screening and Preliminary Validation of Multiple Myeloma Specific Proteins].

OBJECTIVE: To screen novel diagnostic marker or therapeutic target for multiple myeloma (MM). METHODS: Sel1L, SPAG4, KCNN3 and PARM1 were identified by bioinformatics method based on GEO database as high expression genes in MM. Their RNA and protein expression levels in bone marrow mononuclear cells from myeloma cell lines U266, NCI-H929, MM.1s, RPMI8226 and leukemia cell line THP1, as well as 31 MM patients were evaluated by RT-PCR and Western blot, respectively. Meanwhile, 5 samples of bone marrow from healthy donors for allogeneic hematopoietic stem cell transplantation were employed as co…