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Effectiveness of venetoclax based therapy in t(11;14) multiple myeloma with extensive extramedullary disease: a case report.

Extramedullary disease in patients with newly diagnosed multiple myeloma is rare and, despite the abundance of new therapeutic options, is still associated with a dismal prognosis, classifying as an unmet clinical need. Here, we report the case of a young woman diagnosed with multiple myeloma and extensive extramedullary disease characterised by diffuse lymph node involvement. The patient received multiple chemotherapy regimens proving to be refractory to all of them and ultimately benefited from salvage therapy with Venetoclax combination therapy, with a complete disappearance of the extramed…

An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden.

Bispecific T-cell engagers (TCEs) targeting B-cell maturation antigen (BCMA) and CD3, induce deep hematologic responses in ∼60% of heavily pretreated patients with multiple myeloma (MM). We and others found that high tumor burden leads to resistance to TCE and novel strategies are urgently needed to improve responses in this setting. Ikaros degraders, including immunomodulatory drugs (IMiDs) and cereblon E3 ligase modulatory drugs (CELMoDs), represent logical partners for TCEs due to their direct anti-MM effects and additional immune-stimulatory activity; however, it is unclear how to optimall…

Landscapes of immunoglobulin heavy-chain gene repertoire and its cytogenetic abnormalities in Chinese patients with multiple myeloma.

Multiple myeloma (MM) is a heterogeneous disease, the full understanding of whose pathogenesis remains elusive. While B-cell receptors are known to play a pivotal role in myeloma pathogenesis, the characterization of immunoglobulin heavy-chain (IGH) gene repertoire and their clinical significance in Chinese patients has not been fully explored. In this study, we analyzed the profiling of clonal IGH gene rearrangements via NGS assay, and its cytogenetic abnormalities by FISH in a cohort of 301 Chinese patients with newly diagnosed MM. We identified a particular subgroup, which was characterized…

Inflammatory markers from routine blood tests predict survival in multiple myeloma: a Systematic Review and meta-analysis.

BACKGROUND: Multiple myeloma (MM) is an incurable hematologic malignancy marked by abnormal plasma cell proliferation. Inflammatory indices derived from routine blood tests-such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), red cell distribution width (RDW), RDW-to-platelet ratio (RPR), and hemoglobin-to-RDW ratio (HRR)-have shown prognostic value across cancers. This meta-analysis aimed to evaluate their prognostic significance in MM. METHODS: Following PRISMA guidelines, a systematic search of PubMed, Embase, and Web of Scie…

A Case of Kappa Light-Chain Multiple Myeloma With Auer Rod-Like Inclusions and Snapper-Schneid Granules.

In multiple myeloma, plasma cells can display intracellular and intranuclear inclusions. This case report highlights the coexistence of basophilic Snapper-Schneid granules and Auer rod-like cytoplasmic inclusions. A 73-year-old female patient, with a history of hyperlipidemia, rheumatoid arthritis, and hypertension, presented with swelling in both upper extremities. Subsequent evaluations revealed significant proteinuria, hypercalcemia, and atypical plasma cells characteristic of multiple myeloma, with both Auer rod-like inclusions and Snapper-Schneid granules observed. Auer rod-like inclusion…

Influence of PSMB6 and PSMB9 Genetic Polymorphisms on Bortezomib-Based Therapy Response in Newly Diagnosed Multiple Myeloma.

BACKGROUND: Bortezomib (BTZ)-based regimens play a crucial role in the treatment of multiple myeloma (MM), significantly improving patient outcomes. BTZ, a proteasome inhibitor, interferes with cellular processes essential for cancer cell growth and survival, resulting in high response rates. Its use in initial and recurrent treatment strategies has been associated with extended disease control and improved long-term outcomes, contributing to overall survival. This study aimed to delineate the clinical characteristics of newly diagnosed MM patients and investigate the influence of single nucle…

Single-Cell Transcriptome Analysis Reveals the Effect of MIF on Myeloid-Derived Suppressor Cells in Multiple Myeloma.

INTRODUCTION: Multiple myeloma (MM) is a highly lethal hematologic malignancy. Myeloid-derived suppressor cells (MDSCs) exert vital effects on myeloma cells in the bone marrow microenvironment. Macrophage migration inhibitory factor (MIF) is a chemokine-like inflammatory cytokine that can not only prevent the free movement of macrophages but also regulate innate and adaptive immune responses. This study intends to explore the relationship between MIF and MDSCs in the bone marrow microenvironment. METHODS: Single-cell RNA sequencing (scRNA-seq) analysis was performed based on the GSE124310 dat…

Enhanced CAR-T cell function and mitochondrial fitness from earlier unfractionated stem cell product in multiple myeloma.

Chimeric antigen receptor T (CAR-T) cells targeting B cell maturation antigen (BCMA) have changed the treatment landscape for patients with relapsed and refractory multiple myeloma. However, T cell dysfunction associated with progressive disease and multiple prior lines of therapy (PLOT) raises concerns about the feasibility of consistently manufacturing effective CAR-T cells. We investigated the practicality of utilizing previously cryopreserved mobilized apheresis to generate potent anti-BCMA CAR-T cells. Paired patient samples collected longitudinally from (1) mobilized, unfractionated aphe…

Key predictors of long-term outcomes in BCMA-targeted CAR-T therapy for relapsed/refractory multiple myeloma.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy exhibits high response rates in patients with relapsed/refractory multiple myeloma (r/r MM). However, the specific factors that influence the response duration remain poorly understood. METHODS: This single-centre, retrospective observational study included 56 patients with r/r MM who received BCMA CAR-T therapy (equecabtagene autoleucel) at Tongji Hospital, China. We analysed response rates and long-term clinical outcomes and identified key factors contributing to the long-term efficacy of …

Indirect Comparison of Linvoseltamab Versus Teclistamab for the Treatment of Triple-Class Exposed Relapsed/Refractory Multiple Myeloma.

BACKGROUND: B-cell maturation antigen (BCMA) bispecific antibodies have advanced treatment of relapsed/refractory multiple myeloma (RRMM), but comparative data are lacking. METHODS: An unanchored matching-adjusted indirect comparison (MAIC) was conducted between linvoseltamab and teclistamab in triple-class exposed (TCE) RRMM using patient-level data from LINKER-MM1 (117 patients, linvoseltamab 200 mg, data cutoff 1/2024, median follow-up [mFU] 14.3 months) and aggregate data from MajesTEC-1 (165 patients, teclistamab 1.5 mg/kg, data cutoff 2/2022, mFU 14.1 months). Ten LINKER-MM1 patients wi…

Evaluation of Delayed Initiation of Lenalidomide Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Although allogeneic hematopoietic stem cell transplantation (allo-HCT) is considered a potentially curative therapy for multiple myeloma, disease progression after allo-HCT remains a major limitation. Post-transplant maintenance therapy may help reduce the risk of relapse. Lenalidomide, an immunomodulatory agent, has demonstrated efficacy in multiple myeloma, but its use after allo-HCT is limited due to concerns regarding graft-versus-host disease (GVHD). To evaluate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of lenalidomide when used as maintenance therapy after allo-HC…

Prospective real-world evaluation of t(11;14) prevalence and disease biology in multiple myeloma: MEDICI study analysis.

Genetic abnormalities in multiple myeloma (MM) influence treatment outcomes and may inform therapeutic decisions. The most common chromosomal translocation in MM is t(11;14); however, its role in disease progression is not well defined. We report results from MEDICI, a global, minimally invasive, prospective study evaluating t(11;14) status in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM). MEDICI enrolled adult patients (≥18 years) with MM with bone marrow (BM) aspirates collected at diagnosis and/or disease relapse. The primary objective was to determine t(11;14) prevalence in p…

Belantamab mafodotin does not induce B-cell maturation antigen loss or systemic immune dysfunction in multiple myeloma.

Various drug classes target B-cell maturation antigen (BCMA) including chimeric antigen receptor T-cell (CAR T) therapies, bispecific antibodies (bsAb), and antibody-drug conjugates (ADC). Outcomes with CAR T and bsAb therapies in multiple myeloma (MM) have been affected by T-cell exhaustion, and abrogated expression/mutation of the BCMA target has been observed with anti-BCMA therapies. Optimal anti-BCMA sequencing strategies are needed to improve long-term clinical outcomes. We used data from multiple clinical studies of the ADC belantamab mafodotin (as monotherapy and combination regimens) …

Multiple myeloma associated long non-coding RNA PLUM confers chemoresistance by enhancing PRC2 mediated UPR pathway activation.

Multiple myeloma (MM) is the second most common hematological malignancy that displays diverse genetic heterogeneity leading to treatment resistance. Recurrent mutations causing hyperactivation of the non-canonical NF-ĸB pathway are highly prevalent in relapsed, refractory MM patients, but the precise mechanisms driving chemoresistance are poorly understood. Here, we identify a long non-coding RNA termed PLUM, that is overexpressed in NF-ĸB mutant high-risk MM subtypes and patients who are refractory to VRd treatment regimen. Mechanistically, PLUM interacts with Polycomb Repressive Complex 2 t…

MRD contamination in peripheral blood autologous stem cell grafts: implications for relapse and prognosis in multiple myeloma.

A large number of clinical studies have shown that the detection of contamination with clonal plasma cells (CPCs) in peripheral blood autologous stem cell grafts by flow cytometry, next-generation sequencing (NGS), next-generation flow cytometry (NGF), and other methods can reflect the residual tumor burden of multiple myeloma (MM) patients before autologous stem cell transplantation (ASCT). Despite the disadvantages of single-time and unsustainable monitoring, the MRD detection of stem cell grafts remains a negative prognostic factor that reduces overall survival. However, it must be acknowle…

Осколки периферальной крови, полученные в результате ТРНК, являются новыми неинвазивными биомаркерами для диагностики и прогнозируемой стратификации в множестве миеломы.

В последнее время в качестве критически важных регуляторов в области онкологической биологии появились небольшие РНК, полученные в результате передачи РНК; однако их профили экспрессии и клиническая значимость в нескольких миеломах (ММ) по-прежнему плохо определены. МЕТОДЫ: Секвенирование высокой производительности было проведено для всеобъемлющей характеристики профилей выражения ТСНК в периферийных моноядерных клетках крови (ПБМК) из 22 новые пациенты с диагнозом MM и 19 здоровый контроль. Общие целевые гены были предсказаны путем интеграции MiRanda и TookScan, и была создана сеть взаимодейс

Совпадение в аннотации оригинала
BACKGROUND: Transfer RNA-derived small RNAs (tsRNAs) have recently emerged as critical regulators in cancer biology; yet their expression profiles and clinical relevance in multiple myeloma (MM) remain poorly defined. METHODS: High-throughput sequencing was performed to comprehensively characterize tsRNA expression profiles in peripheral blood mononuclear c…

Is surgery for multiple myeloma-related spinal involvement associated with higher blood loss compared to spinal metastases?

PURPOSE: Multiple myeloma (MM) is a hematologic malignancy often presenting with diffuse osteolysis of bone in the vertebral column. So far, little is known about the risk of perioperative blood loss in spinal surgery, as MM-related spinal lesions are often grouped with spinal metastases (SPMs). A more definitive understanding of bleeding risks for myeloma specifically will improve surgical planning and treatment. This study aims to assess the bleeding index (BI) and visually estimated blood loss (EBL) in MM patients versus SPM patients undergoing oncological spine surgery. METHODS: In this r…

Lambda Light Chain Multiple Myeloma in a 47-Year-Old Female Patient on Long-Term Clozapine Therapy.

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia and schizoaffective disorder. While its hematologic toxicities, such as neutropenia and agranulocytosis, are well-documented, emerging studies suggest a rare but concerning association between long-term clozapine use and hematologic malignancies. We present a case of multiple myeloma (MM) in a 47-year-old woman with a 10-year history of clozapine use for schizoaffective disorder. The patient was admitted with orthostasis, fatigue, and acute kidney injury following a gastrointestinal illness. Initial workup reveal…

Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma.

BACKGROUND: Human Herpesvirus (HHV) is a double-stranded DNA virus with a size of 120 to 260 nm. HHV is divided into three subclassifications including herpesvirus alpha, herpesvirus beta, herpesvirus gamma. The HHV group could infect the human body including the orofacial area with mild to severe symptoms. This case report will discuss the diagnostic approach by recognizing the characteristics of each HHV group infection. CASE PRESENTATION: A 23-year-old male patient with complaints of mouth ulcers since 7 day, accompanied by pain when swallowing which was preceded by a fever. Extraoral exam

Disseminated Bartonella henselae Infection in a Patient With Relapsed/Refractory Multiple Myeloma Following Autologous Stem Cell Transplantation.

Bartonella henselae is the causative agent of cat scratch disease (CSD), a zoonotic illness primarily transmitted to humans through scratches or bites from cats and, less commonly, by cat fleas or lice. While the most common presentation is self-limited regional lymphadenopathy in immunocompetent individuals, in immunocompromised patients, such as organ transplant recipients, it can cause systemic infections. This report describes a case of disseminated B. henselae infection in a 66-year-old man with relapsed/refractory multiple myeloma following conditioning chemotherapy and autologous stem c…