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Macrophage activation syndrome-like (MAS-L) manifestations following BCMA-directed CAR T cells in multiple myeloma.

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… T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016;128(13):1688–1700. doi: 10.1182/blood-2016-04-711903. 2. Brudno JN, Maric I, Hartman SD, et al. … B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019;129(6):2210–2221. doi: 10.1172/JCI126397. 4. Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-Cell therapy bb2121 in relapsed or refractory multiple myeloma. …

Subclone-specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single-cell transcriptomics.

Virtually all patients with multiple myeloma become unresponsive to treatment over time. Relapsed/refractory multiple myeloma (RRMM) is accompanied by the clonal evolution of myeloma cells with heterogeneous genomic aberrations and profound changes of the bone marrow microenvironment (BME). However, the molecular mechanisms that drive drug resistance remain elusive. Here, we analyze the heterogeneous tumor cell population and its complex interaction network with the BME of 20 RRMM patients by single cell RNA-sequencing before/after treatment. Subclones with chromosome 1q-gain express a specifi…

Symptom burden in transplant ineligible patients with newly diagnosed multiple myeloma: a population-based cohort study.

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… While much progress has been made in the therapeutics for newly-diagnosed multiple myeloma (NDMM) patients, including transplant-ineligible patients, MM remains an incurable malignancy. … Trajectory of symptom burden in patients with newly diagnosed multiple myeloma. …

Characteristics and outcomes of therapy-related myeloid neoplasms following autologous stem cell transplantation for multiple myeloma.

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… Fig. 1 Survival of multiple myeloma (MM) patients that underwent autologous SCT and developed therapy-related myeloid neoplasm (t-MN). … McCarthy PL Lenalidomide after stem-cell transplantation for multiple myeloma N. Engl. J. Med. 2012 366 1770 1781 10.1056/NEJMoa1114083 22571201 PMC3744390 6. Attal M Lenalidomide maintenance after stem-cell transplantation for multiple myeloma New England J. …

Multiple myeloma with t(11;14)-associated immature phenotype has lower CD38 expression and higher BCL2 dependence.

CD38 expression on myeloma cells is a critical factor affecting the early response to the anti-CD38 antibody daratumumab. However, factors affecting CD38 expression in untreated multiple myeloma are not fully elucidated. In this study, we found that CD38 expression was significantly lower in myeloma patients with the translocation t(11;14)-associated immature plasma cell phenotype, and particularly in those expressing B-cell-associated genes such as PAX5 and CD79A. CD138, a representative marker of plasmacytic differentiation, was also significantly lower in these patients, suggesting that CD3…

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics.

Treatment benefit in multiple myeloma (MM) patients with high-risk cytogenetics remains suboptimal. The phase 3 ICARIA-MM trial (NCT02990338) showed that isatuximab plus pomalidomide-dexamethasone prolongs median progression-free survival (mPFS) in patients with relapsed/refractory MM (RRMM). This subgroup analysis of ICARIA-MM compared the benefit of isatuximab in high-risk [defined by the presence of del(17p), t(4;14) or t(14;16)] versus standard-risk patients. The efficacy of isatuximab in patients with gain(1q21) abnormality was also assessed in a retrospective subgroup analysis. In ICARIA…

Light Chain Multiple Myeloma: High Serum Free Light Chain Concentrations Portend Renal Damage and Poorer Survival.

BACKGROUND: Monoclonal immunoglobulins provide an indication of the tumor burden in patients with plasma cell neoplasms. Higher concentrations of serum free light chains in light chain predominant multiple myeloma have been shown to correlate with a poorer outcome. We examined the correlations of serum free light chain concentrations in light chain myelomas with survival, estimated glomerular filtration rate (eGFR) and other clinical and pathological parameters. METHODS: Records of patients with light chain multiple myelomas were reviewed. Highest concentration of serum free light chains for …

Elevation of miR-302b prevents multiple myeloma cell growth and bone destruction by blocking DKK1 secretion.

BACKGROUND: Myeloma bone disease (MBD) is a severe complication of multiple myeloma (MM) mainly due to an imbalance between enhanced osteoclast activity and reduced osteoblast function. Previous studies have demonstrated that miRNAs play a vital role in the osteogenic differentiation of mesenchymal stromal cells (MSCs) in MM. However, the value of miR‑302b in MBD remains to be further elucidated. The aim of this study is to explore the role of miR‑302b in the regulation of MBD osteogenic differentiation and evaluate the potential of a new therapeutic strategy for the clinical treatment of MBD.…

Light chain Amyloidosis (AL) associated with multiple myeloma revealed by peripheral bilateral polyarthritis: a case report.

In chronic polyarthritis, the presence of macroglossia with absence of rheumatoid factor and anti-CCP antibodies may be suggestive of amyloid arthopathy. Clinical evaluation takes precedence over classification criteria.

Targeting LAG3/GAL-3 to overcome immunosuppression and enhance anti-tumor immune responses in multiple myeloma.

Immune profiling in patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM) provides the framework for developing novel immunotherapeutic strategies. Here, we demonstrate decreased CD4+ Th cells, increased Treg and G-type MDSC, and upregulation of immune checkpoints on effector/regulatory and CD138+ cells in MM patients, compared MGUS/SMM patients or healthy individuals. Among the checkpoints profiled, LAG3 was most highly expressed on proliferating CD4+ Th and CD8+ Tc cells in MM patients BMMC and PBMC. Treatment wi…

Case report: simultaneous occurrence of multiple myeloma and non-Hodgkin lymphoma treated by CAR T therapy.

RATIONALE: B cell lymphoma can co-occur with multiple myeloma (MM), and the prognosis in this case is usually poor. We propose the combination of CD19-chimeric antigen receptor (CAR) T cells and BCMA-CAR T cells for the treatment of such patients to obtain a superior prognosis. PATIENT CONCERNS: We present a 50-year-old patient with previous B cell lymphoma and subsequent multiple myeloma (MM). DIAGNOSIS: A diagnosis of B cell lymphoma and MM was made. INTERVENTIONS: The patient was treated with a combination of haploidentical CD19-chimeric antigen receptor (CAR) T cells and BCMA-CAR T cell…

Depressive symptoms, mental health-related quality of life, and survival among older patients with multiple myeloma.

PURPOSE: To examine the impact of pre-diagnosis depressive symptoms and mental health-related quality of life (HRQOL) on survival among older patients with multiple myeloma (MM). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource. Patients aged 65 years and older diagnosed with first primary MM between 1998 and 2014 were identified, and presence of depressive symptoms was determined based on responses to 3 depression screening questions prior to MM diagnosis. Veterans RAND 12 mental component s…

KRD-PACE Mobilization for Multiple Myeloma Patients With Significant Residual Disease Before Autologous Stem-Cell Transplantation.

BACKGROUND: Bortezomib has been incorporated into thalidomide and dexamethasone provided with cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE) as an intensive regimen before autologous stem-cell transplantation for multiple myeloma (MM). We examined MM patients at our center who received chemomobilization with a regimen that substituted carfilzomib and lenalidomide for bortezomib and thalidomide (KRD-PACE). PATIENTS AND METHODS: This was a retrospective study of 27 MM patients who received KRD-PACE for chemomobilization. Our analysis included patients who had circulating plasma …

Targeted Disruption of Bone Marrow Stromal Cell-Derived Gremlin1 Limits Multiple Myeloma Disease Progression In Vivo.

In most instances, multiple myeloma (MM) plasma cells (PCs) are reliant on factors made by cells of the bone marrow (BM) stroma for their survival and growth. To date, the nature and cellular composition of the BM tumor microenvironment and the critical factors which drive tumor progression remain imprecisely defined. Our studies show that Gremlin1 (Grem1), a highly conserved protein, which is abundantly secreted by a subset of BM mesenchymal stromal cells, plays a critical role in MM disease development. Analysis of human and mouse BM stromal samples by quantitative PCR showed that GREM1/Grem…

[Autologous haematopoietic stem cell transplantation in patients with multiple myeloma complicated by dialysis-dependent renal failure].

AIM: To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure. MATERIALS AND METHODS: During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/…

Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma.

Monitoring malignant progression and disease recurrence post-therapy are central challenges to improving the outcomes of patients with multiple myeloma (MM). Whereas current detection methods that rely upon bone marrow examination allow for precise monitoring of minimal residual disease and can help to elucidate clonal evolution, they do not take into account the spatial heterogeneity of the tumor microenvironment. As such, they are uninformative as to the localization of malignant plasma cells and may lead to false negative results. With respect to the latter challenge, clinically-available i…

Using Prognosis-Related Gene Expression Signature and Connectivity Map for Personalized Drug Repositioning in Multiple Myeloma.

BACKGROUND Multiple myeloma (MM) is the second most common hematologic cancer with poor prognosis. Novel therapeutic strategies are needed to decrease the high mortality rate. The aim of this study was to identify prospective agents for MM. MATERIAL AND METHODS A microarray dataset was mined, which contains the transcriptome profiles of 588 MM patients. Univariate Cox analysis was performed to analyze the relationships between genes and clinical outcome. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were determined. Protective and risky genes were uploaded to Connec…

Pomalidomide-Responsive Extramedullary Myeloma Relapsed after Allogeneic Hematopoietic Transplant and Refractory to Multiple Lines of Chemotherapy.

Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide…