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Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma.

BackgroundBecause patients with newly diagnosed multiple myeloma (NDMM) do not always receive any treatment beyond first-line (1L) therapy, it is imperative that patients receive the best treatment in the 1L setting. However, the optimal initial treatment remains to be identified. We performed a clinical simulation to assess potential outcomes with different treatment sequences.Patients and methodsWe used a partitioned survival model to compare overall survival (OS) with (1) daratumumab, lenalidomide, and dexamethasone (D-Rd) in 1L followed by a pomalidomide- or carfilzomib-based regimen in se

Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial.

PURPOSE: To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study. PATIENTS AND METHODS: PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs. RESULTS: A total of 737 transplant-ineligible (TIE) patie

Daratumumab плюс VRd в японских пациентах, имеющих право на трансплантацию/отсроченные заболевания NDMM: японская подгруппа по испытанию CEPHEUS.

:: фазы 3 Судебное разбирательство по делу CEPHEUS было проведено в 13 начиная с декабря 11, 2018 в случае пациентов с недавно поставленным диагнозом множественной миеломы (НДММ), которые имели право на трансплантацию или для которых трансплантация не была запланирована в качестве первоначальной терапии. Бортезомиб, линалидомид и дексаметасон (VRd) с даратумумабом (D-VRd) дали более глубокие и долгосрочные ответные меры и снизили риск развития заболеваний или смерти по сравнению с VRd. В ходе этого анализа была проведена оценка эффективности и безопасности D-VRd, в частности в японском поднасе

Лечение для пожилых пациентов из числа миеломы.

Замечательные успехи были достигнуты в лечении нескольких пациентов, страдающих миеломой (ММ); однако для слабых пожилых пациентов эти результаты лечения по-прежнему недостаточны. Увеличивается число пожилых пациентов с МР, равно как и число пациентов, проходящих курс лечения. Существует повышенный спрос на оценку этих пациентов в целях обеспечения оптимальных методов лечения. Несмотря на то, что непрерывное лечение чаще случается у пациентов с ОМ по сравнению с стационарным лечением, из-за риска прерывания лечения, что приводит к снижению показателей выживаемости, важное значение имеют эффект

Defining the Role of Oral Pathway Inhibitors as Targeted Therapeutics in Arteriovenous Malformation Care.

Arteriovenous malformations (AVMs) are vascular malformations that are prone to rupturing and can cause significant morbidity and mortality in relatively young patients. Conventional treatment options such as surgery and endovascular therapy often are insufficient for cure. There is a growing body of knowledge on the genetic and molecular underpinnings of AVM development and maintenance, making the future of precision medicine a real possibility for AVM management. Here, we review the pathophysiology of AVM development across various cell types, with a focus on current and potential druggable

The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma.

Multiple myeloma (MM) remains largely incurable despite enormous improvement in the outcome of patients. Over the past decade, we have witnessed the "era of monoclonal antibody (moAb)", setting new benchmarks in clinical outcomes for relapsed and newly diagnosed MM. Due to their excellent efficacy and relative safe toxicity profile, moAbs in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have become the new backbone of upfront anti-MM therapy. Yet, most patients will eventually relapse and patients who become refractory to IMiDs, PIs and moAbs have a dismal out

A systematic framework for predictive biomarkers in immune effector cell-associated neurotoxicity syndrome.

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the management of several life-threatening malignancies, often achieving durable sustained responses. The number of patients treated with this new class of cell-based therapy, along with the number of Food and Drug Association (FDA) approved indications, are growing significantly. Unfortunately Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) can often occur after treatment with CAR-T cells, and severe ICANS can be associated with significant morbidity and mortality. Current standard treatments are mainly steroids

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Endotheliopathy in CAR T-Cell Therapy: Mechanistic Insights into the VWF/ADAMTS13 Axis and the Angiopoietin-Tie2 Pathway.

Chimeric antigen receptor (CAR) T cell therapy has transformed the management of hematologic malignancies, yet its clinical success is tempered by severe immune-mediated toxicities, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), often accompanied by CAR T cell therapy-related coagulopathy (CARAC). Converging evidence identifies therapy-related endotheliopathy as a central pathophysiological link between cytokine excess, hemostatic dysregulation, capillary leak, and organ injury. Parallel efforts aim to identify circulating biomarke

Abnormalities in alternative splicing of angiogenesis-related genes and their role in HIV-related cancers.

Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer. This aberra

Бремя лечения, секвенирования и использования ресурсов здравоохранения в множестве миеломы в Латинской Америке: обзор целевой литературы.

Утверждение основных классов лекарственных препаратов позволило улучшить выживание пациентов с множественной миеломой (ММ). В то же время большинство пациентов сталкиваются с рецидивом или становятся противниками этих методов лечения, причем повторное лечение имеет ограниченную эффективность. Доступ к этим основным методам лечения в разных странах Латинской Америки (ЛАТАМ), что может привести к неоптимальным клиническим результатам. Цель этого целевого обзора литературы заключалась в том, чтобы понять эпидемиологию, бремя лечения, последовательность лечения и наличие MM в Аргентине, Бразилии,

Perspectives on the Treatment of Multiple Myeloma.

The treatment of multiple myeloma has evolved significantly over the past few decades with the development of novel therapeutics. The introduction of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and high-dose chemotherapy followed by hematopoietic stem cell transplantation has led to improved response rates and survival outcomes. The use of bispecific antibodies and chimeric antigen receptor T-cell therapy is currently under study, and early results are showing promise. Although outcomes for patients with MM have improved with the development of new treatments, there r

An amino-terminal BRAF deletion accounting for acquired resistance to RAF/EGFR inhibition in colorectal cancer.

Although combination therapy with RAF and EGFR inhibitors has improved the survival outcomes of patients with BRAF-mutated colorectal cancer (CRC), acquired resistance invariably develops. The mechanisms of acquired resistance to RAF inhibitors have been largely attributed to activating mutations in RASgenes, MAP2K mutations, and amplifications in BRAF, RAS genes, and EGFR In this report, we describe a patient with BRAF-mutated CRC who acquired an amino-terminal BRAF deletion involving the Ras-binding domain (RBD) after treatment with RAF/EGFR inhibitor therapy. Amino-terminal BRAF deletions i

Minimal residual disease in solid tumors: Clinical applications and future directions.

Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA) has emerged as a dynamic biomarker for MRD detection. It enables real-time disease monitoring, prognostication, and often therapeutic decision-making. Two major ctDNA approaches exist, tumor-informed and tumor-agnostic, and they differ in sensitivity, specificity, and clinical feasibility. Recent clinical trials have supported a prognostic and predictive utili

Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogen

Visfatin promotes multiple myeloma cell proliferation and inhibits apoptosis by inducing IL-6 production via NF-κB pathways.

BackgroundMultiple myeloma (MM) is the second most prevalent hematological malignancy that results in the proliferation of malignant plasma cells and the overproduction of monoclonal immunoglobulin. Visfatin plays an important role in the regulation of apoptosis, oxidative stress, and inflammation; however, to this date, the role of visfatin in multiple myeloma is unclear.ObjectiveTo explore the role of visfatin in multiple myeloma and find new targets for MM treatment.MethodsIn this study, expression of visfatin in bone marrow was detected by ELISA. The diagnostic value of visfatin was determ

Measurable Residual Disease Testing in Multiple Myeloma Following T-Cell Redirecting Therapies.

Several novel T-cell-based therapies have recently become available for multiple myeloma (MM). These T-cell redirecting therapies (TRTs) include chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BiAbs). In both clinical trial and real-world data, these therapies have demonstrated high rates of deep clinical response, and some are now approved for second-line treatment for relapsed MM. The deep and sustained clinical responses these therapies are capable of inducing will require sophisticated response monitoring to provide meaningful information for patient care. Obtaining me

Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.

Vascular endothelial growth factor (VEGF) signaling is a critical regulator of vasculogenesis, angiogenesis, and lymphangiogenesis, processes that are vital for the development of vascular and lymphatic systems, tissue repair, and the maintenance of homeostasis. VEGF ligands and their receptors orchestrate endothelial cell proliferation, migration, and survival, playing a pivotal role in dynamic vascular remodeling. Dysregulated VEGF signaling drives diverse pathological conditions, including tumor angiogenesis, cardiovascular diseases, and ocular disorders. Excessive VEGF activity promotes tu

Molecular targeted therapy for anticancer treatment.

Since the initial clinical approval in the late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served as a fundamental backbone in precision medicine for cancer treatment. These approaches are now used clinically as first-line therapy for various types of human cancers. Compared to conventional chemotherapy, targeted therapeutic agents have efficient anticancer effects with fewer side effects. However, the emergence of drug resistanc

miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy.

Immunotherapy is presently one of the most promising areas of investigation and development for the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies and chimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuable therapeutic options, the goal of cure has not yet been achieved for most malignancies and more efforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucial molecular signaling pathways. Recent

Bedside implications of the use of surrogate endpoints in solid and haematological cancers: implications for our reliance on PFS, DFS, ORR, MRD and more.

Clinical endpoints, such as overall survival, directly measure relevant outcomes. Surrogate endpoints, in contrast, are intermediate, stand-in measures of various tumour-related metrics and include tumour growth, tumour shrinkage, blood results, etc. Surrogates may be a time point measurement, that is, tumour shrinkage at some point (eg, response rate) or biomarker-assessed disease status, measured at given time points (eg, circulating tumour DNA, ctDNA). They can also be measured over time, as with progression-free survival, which is the time until a patient presents with either disease progr