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Outcomes of Newly Diagnosed Multiple Myeloma Patients Requiring Dialysis.

INTRODUCTION: Renal impairment (RI) is a common complication in newly diagnosed multiple myeloma (NDMM), with 1-5% of patients presenting with severe RI requiring dialysis, which is associated with significant morbidity and early mortality. Limited real-world data exist on outcomes for these patients. AIM/METHODS: We assessed renal response patterns and outcome determinants in 73 consecutive NDMM patients requiring dialysis, treated in a single centre (2010 to 2023). RESULTS: Median age was 69 years; 52% had high-risk cytogenetics. All patients received bortezomib-based induction therapy (19…

CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy.

Glucocorticoids (GC) are cornerstone drugs in the treatment of multiple myeloma (MM). Because MM cells exploit the bone marrow microenvironment to obtain growth and survival signals, resistance to glucocorticoid-induced apoptosis emerges, yet the underlying mechanisms remain poorly characterized. Here, we identify that the chemokine receptor CCR1, together with its main ligand CCL3, plays a pivotal role in reducing the glucocorticoid sensitivity of MM cells. We show that blocking CCR1 signaling with the antagonist BX471 enhances the anti-MM effects of the glucocorticoid dexamethasone in MM cel…

Methylation variability and LINE-1 activation in multiple myeloma.

Multiple myeloma (MM) is a type of hematological cancer that arises from uncontrolled proliferation of plasma cells. In addition to frequent genetic mutations, malignant plasma cells are characterized by alterations to the epigenome. Myeloma cells display a genome-wide loss of DNA methylation and a corresponding increase in 'active' chromatin modifications. The dramatic epigenetic remodeling that occurs in cancer genomes is associated with loss of silencing at transposable elements, which can impact genome regulation. Through paired epigenome and transcriptome profiling of patient derived MM s…

Intracranial multiple myeloma masquerading as subdural hematoma: illustrative cases.

BACKGROUND: Intracranial involvement in multiple myeloma (MM) is a rare clinical presentation, often mimicking other conditions such as subdural hematoma (SDH) and resulting in poor prognosis. OBSERVATIONS: This case series highlights 2 older female patients, one with a prior diagnosis of MM, who developed subdural masses resembling SDH. Both cases were associated with significant cerebral edema and mass effect. Biopsies confirmed plasma cell neoplasms, and both patients underwent tailored treatment, including corticosteroids, radiation therapy, and systemic chemotherapy. The patients showed …

Newly Diagnosed High-Risk Multiple Myeloma: Outcomes and Management.

Multiple myeloma (MM) is a heterogeneous hematologic malignancy, with high-risk cytogenetic abnormalities (HRCAs) such as del(17p), t(4; 14), t(14; 16), and gain(1q) contributing to poor prognosis in approximately 20%-25% of newly diagnosed patients. These abnormalities are associated with aggressive disease, frequent relapses, and inferior progression-free and overall survival. This review explores the evolving therapeutic landscape for high-risk MM, focusing on induction strategies for both transplant-eligible and transplant-ineligible patients, the role of autologous stem cell transplantati…

Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis.

Proteasome inhibitors are currently at the forefront of multiple myeloma (MM) treatment. Drug resistance in MM challenges treatment, causing relapses and making the disease incurable. Urgent strategies are needed to combat resistance and understand its mechanisms. Targeting the metabolism of MM is a promising approach, as metabolic changes are associated with the disease and its adaptation to therapy. Metabolomics, the study of small molecule metabolites, is a powerful tool for identifying and analyzing a cell's metabolic phenotype. In this study, we aimed to investigate alterations in the met…

Challenges facing CAR T-cell immunotherapy in multiple myeloma.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated considerable promise in patients with late-line refractory multiple myeloma (MM), and there has been commercial approval for its use in treating relapsed and/or refractory MM (RR MM). B-cell maturation antigen remains the most extensively studied CAR T-cell target in this disease, although several alternative antigens are also under active investigation. Despite the notable success of CAR T-cell therapy in the treatment of RR MM, challenges remain in improving response rates, extending the durability of remission, and reducing rel…

Targeting proteostasis in multiple myeloma through inhibition of LTK.

Multiple myeloma (MM) cells secrete high levels of immunoglobulin and are therefore addicted to mechanisms that maintain proteome homeostasis (proteostasis). While proteasome inhibitors that target the degradative aspect of proteostasis have proven effective, only limited attempts have been made to target protein secretion. Here we show that the receptor tyrosine kinase LTK is a regulatory node in the proteostasis network that responds to secretory load and helps cells maintain a high secretory output. LTK is a highly similar paralog to ALK and by repurposing existing ALK inhibitors, we demons…

Patient Preferences on Clinical Decision Making in Multiple Myeloma.

PURPOSE: To better understand the priorities that guide patients with multiple myeloma, we surveyed patients on four different treatment scenarios, each of treatment strategies shown to improve progression-free survival (PFS) but offering similar overall survival (OS) outcomes. METHODS: We conducted a survey using the HealthTree Cure Hub by the HealthTree Foundation, the largest online portal for people with plasma cell dyscrasias. RESULTS: The primary analysis cohort included 466 participants with myeloma, while an additional 297 responses from patients with smoldering myeloma or monoclonal…

Concomitant Transthyretin Amyloid Cardiomyopathy in Patients With Multiple Myeloma.

BACKGROUND: Cardiac amyloidosis is a restrictive cardiomyopathy caused by myocardial deposition of insoluble amyloid fibrils. The 2 most frequent types are transthyretin amyloid cardiomyopathy (ATTR-CM) and light-chain amyloid cardiomyopathy (AL-CM). AL-CM is a type of plasma cell dyscrasia characterized by overproduction of light chains by a plasma cell clone. Some plasma cell dyscrasias, such as monoclonal gammopathy of undetermined significance, are common in patients with ATTR-CM; however, the coexistence of multiple myeloma and ATTR is rarely described in the literature. CASE SUMMARY: We…

Light Chain Multiple Myeloma Diagnosed via Urine Protein Discrepancy.

BACKGROUND: Discrepancies between routine urinalysis and 24-hour urine protein quantification often indicate atypical pathologies. Light chain multiple myeloma (LCMM) secretes free light chains and may present conflicting urine protein results. METHODS: Laboratory analysis was performed, including a urinary immunoglobulin light chain test and a reduction assay to analyze the differences in proteinuria patterns. RESULTS: The urinary immunoglobulin light chain test revealed a large amount of λ-type Bence Jones protein (6,660 mg/L), strongly suggestive of LCMM. This finding highlighted the pres…

Lymphopenia predicts poor outcomes in newly diagnosed multiple myeloma.

Bone marrow microenvironment plays an important role in promoting growth and survival of multiple myeloma (MM) cells. The tumor-promoting immune microenvironment is augmented while antitumor immune responses are inhibited. Although clinical and genomic markers of high-risk MM have been described, the immune status is just being recognized as a potential mediator of disease behavior. This is even more important with the development of a number of immune-based therapies. Based on these considerations, we evaluated peripheral blood absolute lymphocyte count (ALC) as an easily accessible marker re…

Bispecific Antibody Therapy for Multiple Myeloma: A Practical Toolkit.

PURPOSE: Bispecific antibodies emerged as a new class of treatment for patients with relapsed/refractory multiple myeloma. Education on the practicalities of delivery and patient management is vital to optimize outcomes with these novel agents. METHODS: A group of 5 experienced hematologists from centers in the United States, Europe and Latin America met to discuss key considerations for bispecific antibody therapy and agree on best practice advice. RESULTS AND DISCUSSION: This paper presents advice for best practice at each stage of the bispecific antibody therapy patient journey: patient e…

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future Directions.

Relapsed and refractory multiple myeloma (RRMM) remains a challenging condition despite advances in immunotherapies. Novel bispecific antibodies (BsAbs), including talquetamab, have shown promising efficacy in heavily pretreated patients, even those with triple- and penta-refractory disease. Talquetamab, recently approved by the FDA and EMA, is indicated for patients who have progressed after at least three or four prior lines of therapy (LOTs). Administered following a step-up dosing phase to manage cytokine release syndrome (CRS), talquetamab demonstrated a high overall response rate (ORR) o…

Current Treatment Strategies for Multiple Myeloma at First Relapse.

Multiple myeloma (MM), the second most common hematologic cancer, remains an incurable malignancy, characterized by an initial response to therapy followed by successive relapses. The upfront treatment typically involves induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance therapy. It is important to note that the anticipated duration of myeloma response diminishes with each subsequent relapse. Therefore, the first relapse represents a critical juncture in treatment, where refractoriness to key drug classes emerges as a significant challenge.…

Long-Term Survival with Multiple Myeloma: An Italian Experience.

Background/objectivesTreatments for multiple myeloma (MM) have expanded in the last decade, and the overall survival (OS) of MM patients (pts) is in continuous improvement. With the availability of new treatments and the use of high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation (ASCT), the median OS of newly diagnosed MM (NDMM) pts is 6-8 years. To date, approximately 50% and 28% of MM patients are still alive at 5 years and 10 years. Few data are reported concerning the characteristics of the long-term survival MM pts.Methodsthe aim of this observational mu…

T-Cell Aptioners in Multieloma: Клинический обзор.

Технологи T-клеток (TCE) сконструированы таким образом, чтобы связывать как субъект CD3 на Т-клетки, так и конкретные антигены на клетки опухоли, вызывая активацию Т-клеток и лизиз клеток опухоли. TCE, предназначенные для антигена созревания клеток В (BCMA) и рецептора с соединениями G-протеинов, класс C, группа 5, член D (GPRC5D) продемонстрировал значительную клиническую активность у пациентов, прошедших интенсивную предварительную обработку, с множественным миеломой (RRMM). В качестве монотерапии ПТО имеют общий коэффициент ответов (ОРС) выше 60%, с глубокими и прочными гематологическими ре

Совпадение в аннотации оригинала
T-cell engagers (TCEs) are engineered to bind both the CD3 subunit on T-cells and specific antigens on tumor cells, triggering T-cell activa … demonstrated significant clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). As a monotherapy, TCEs have had overall response rates (ORRs) of over 60%, with deep and durable hematological responses. Common toxicities include cytokine release syndrome (CRS), infections, and on-target off-tumor effects. Ongoing researc …

Moderate-Severe Thrombocytopenia Portends Poor Outcomes in Multiple Myeloma.

BACKGROUND: Malignant plasma cells in multiple myeloma (MM) reprogram the bone marrow microenvironment to support tumor expansion. This myeloma cell-hematopoietic stem cell interaction leads to fewer hematopoietic stem cells in the bone marrow and altered differentiation of megakaryocytes, which can contribute to MM disease-related thrombocytopenia. Given the development of novel therapies for MM and the need for biomarkers reflecting the bone marrow microenvironment, we evaluated peripheral blood platelet count at diagnosis and during treatment of MM. METHODS: We retrospectively evaluated 14…