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[Extracellular vesicle-mediated drug resistance in multiple myeloma].

Because of innovative therapeutic agents such as proteasome inhibitors, immunomodulatory medicines, and antibody medications, the prognosis of multiple myeloma (MM) has considerably improved in recent years. However, the prognosis for MM patients with treatment resistance and extramedullary illness remains poor. The interaction between MM cells and their surrounding cells in the bone marrow microenvironment is critical for medication resistance development. Many issues cannot be explained by liquid factors, such as cytokines and chemokines. Extracellular vesicles (EVs) have gained interest due…

Calcium silicate/bortezomib combinatory therapy for multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy. Bortezomib (BOR), a first-generation proteasome inhibitor, is the basic agent for the treatment of MM and has greatly improved the survival of patients with MM. However, the side effects of BOR (e.g. peripheral neuropathy) occur frequently and almost all MM patients eventually develop resistance to BOR and go on to develop refractory relapsed multiple myeloma (RRMM). Therefore, it is of great significance to find a method to increase the sensitivity of MM to BOR to reduce toxicity and drug resistance. Herein, we found that…

Widespread presentation of brown tumors mimicking multiple myeloma.

Brown tumors or osteitis fibrosa cystica has become a rare presentation of primary hyperparathyroidism in up-to-date clinical practice. Here, we describe a case of longstanding untreated hyperparathyroidism presenting itself with brown tumors in a 65-year-old patient. During the diagnostic work-up of this patient, bone SPECT/CT and 18F-FDG-PET/CT revealed multiple widespread osteolytic lesions. Differentiating from other bone tumors such as multiple myeloma is challenging. In this case, the final diagnosis was made by integrating the medical history, biochemical diagnosis of primary hyperparat…

Smoldering Multiple Myeloma: Observation Versus Control Versus Cure.

Smoldering multiple myeloma (SMM) is an intermediate clinical stage in the spectrum of monoclonal plasma cell disorders. It represents a heterogeneous clinically defined condition in which some patients (approximately 50%) have monoclonal gammopathy of undetermined significance (premalignancy), and some (approximately 50%) have multiple myeloma (biologic malignancy). Using specific prognostic factors, patients with SMM, in whom malignant transformation has already likely occurred, can be identified. These patients are considered to have high-risk SMM. Patients with newly diagnosed high-risk SM…

Therapy-related B-lymphoblastic leukemia after multiple myeloma.

New therapies for multiple myeloma have improved outcomes, but are associated with therapy-related hematologic malignancies. We report eight patients with therapy-related B-lymphoblastic leukemias (t-B-ALL) in the setting of therapy for multiple myeloma, which included lenalidomide maintenance. A subset of patients had pancytopenia and low-level marrow involvement by acute leukemia, an unusual finding in de novo B-ALL. One patient died of chemotherapy complications; the other seven responded. No patient died of B-ALL (median follow up of 1.0 years). Our series suggests that t-B-ALL is clonally…

SUMOylation inhibition enhances dexamethasone sensitivity in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an incurable plasma cell malignancy. Although Dexamethasone (Dex) is the most widely used therapeutic drug in MM treatment, patients develop Dex resistance leading to progressive disease, demanding an urgent need to investigate the mechanisms driving Dex resistance and develop new reagents to address this problem. We propose SUMOylation as a potential mechanism regulating Dex resistance and SUMOylation inhibition can enhance Dex sensitivity in MM. METHODS: Using MM cell lines and primary MM samples from relapsing MM patients, we evaluated the effects of kn…

NCCN Guidelines® Insights: Multiple Myeloma, Version 3.2022.

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.

How I treat frontline transplantation-eligible multiple myeloma.

High-dose melphalan supported by autologous transplantation has been the standard of care for eligible patients with newly diagnosed multiple myeloma (MM) for >25 years. Several randomized clinical trials have recently reaffirmed the strong position of transplantation in the era of proteasome inhibitors and immunomodulatory drugs combinations, demonstrating a significant reduction of progression or death in comparison with strategies without transplantation. Immunotherapy is currently changing the paradigm of MM management, and daratumumab is the first-in-class human monoclonal antibody target…

Biochemical profile of Bence-Jones type multiple myeloma.

Multiple myeloma (MM) is a malignant tumor occurring from plasma cells that produce an abnormal monoclonal immunoglobulin - a paraprotein. A distinctive feature of Bence-Jones myeloma is the excretion of monoclonal free light chains of immunoglobulins with 24h urine, and the absence of monoclonal intact immunoglobulins secretion. Comprehensive analysis of biochemical parameters in blood serum and 24h urine in patients with Bence-Jones multiple myeloma using electrophoretic and immunoturbidimetric methods to assess their sensitivity as biomarkers. 50 patients with a morphologically confirmed di…

Granulomatous Lymphocytic Interstitial Lung Disease in Multiple Myeloma.

An 82-year-old woman complained of recurring cough and shortness of breath and was diagnosed with progressive multiple myeloma (MM). Chest computed tomography (CT) revealed bilateral ground-glass opacity and interlobular septal thickening predominantly in the lower lung zones. Histopathologic findings obtained by a transbronchial lung cryobiopsy (TBLC) revealed alveolitis and granulomas consistent with granulomatous-lymphocytic interstitial lung disease (GLILD). Aggressive chemotherapy for MM contributed to the improvement in respiratory symptoms and abnormal chest CT findings. In cases of MM …

Extraosseous Spread of Multiple Myeloma Mimicking Pancoast Tumor.

A 55-year-old man presented with upper backache for one month, inability to move both the lower limbs for two weeks and retention of urine f … ion, concertina collapse of the vertebral body, and pattern of neurological deficit pointed towards multiple myeloma. T2 corpectomy and mesh cage placement, C7-T4 posterior stabilization, and resection of the second rib were done. Histopathology confirmed multiple myeloma. Postoperatively, the patient was managed with radiotherapy and bortezomib. The patient had a …

Post-Transplant Maintenance Treatment Options in Multiple Myeloma.

Maintenance therapy post autologous stem cell transplant (ASCT) is commonly employed in myeloma patients to prolong remission, as relapse invariably occurs after ASCT. After initial diagnosis and risk stratification, patients receive initial therapy with a combination of drugs, typically a proteasome inhibitor and an immunomodulatory imide drug (IMiD), and in those considered eligible, high-dose chemotherapy followed by autologous stem cell transplant. The aim of our study was to review the literature and consolidate evidence regarding different maintenance therapies post stem cell transplant

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… In patients with high-risk multiple myeloma, maintenance therapy with a combination of a proteasome inhibitor and immunomodulatory drug appears to be the best choice based on available data. … Wang Y Sanchez L Siegel DS Wang ML Elotuzumab for the treatment of multiple myeloma J Hematol Oncol 2016 9 1 55 27417553 10.1186/s13045-016-0284-z PMC4946088 54. …

Accelerated single cell seeding in relapsed multiple myeloma.

Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique,…

Multiple myeloma presenting as plasmacytoma causing obstructive jaundice.

Jaundice, weight loss, and anorexia are common symptoms that raise concern for pancreatic malignancy. Although the most common form of pancr … lary plasmacytomas. Here, we present a case of pancreatic plasmacytoma in association with advanced multiple myeloma diagnosed using endoscopic ultrasonography-guided fine-needle aspiration.

Neuro-meningeal cryptococcal infection revealing a multiple myeloma.

Rare cases of Cryptococcus have been documented in patients living with multiple myeloma. To date there has been no documented evidence of cryptococcosis revealing multiple myeloma. We reported a 63-year-old man who had a 2-months history continuous holocranial headaches, morning vomiting, complaining of blurred vision and fever. The biologic and the imaging showed a Cryptococcus meningoencephalitis. The search for a cause of immunodeficiency revealed a multiple myeloma. The diagnosis for Cryptococcus was confirmed according to an India ink stain, blood and cerebrospinal fluid culture. The pat…

Cardiac calcified amorphous tumour associated with multiple myeloma.

We report an 86-year-old woman who was diagnosed with multiple myeloma (MM) and was receiving chemotherapy since the age of 82. A high echoic mass attached to the mitral valve was observed on transthoracic echocardiography 4 years after the treatment. The possibility of malignancy could not be ruled out, and hence, the mass was excised surgically. Pathologically, most of the mass consisted of calcified lesion without tumour tissue, and these findings were not inconsistent with calcified amorphous tumour (CAT). This case suggests that CAT may be associated with MM and has been reported after a …

Management of multiple myeloma during COVID-19 pandemic.

At the end of 2019, a novel coronavirus was identified as the cause of pneumonia cases in Wuhan, a city in the Hubei Province of China. On January 30, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a public health emergency of international concern and, in March 2020, began to characterize it as a pandemic. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) In February 2020, the World Health Organization designated the disease COVID-19, which stands for coronavirus disease 2019.

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… Multiple Myeloma (MM) affects over 32,000 Americans annually [1] . More than 130,000 people are living with the disease, making MM the most common blood cancer in the U.S. population [2] . … relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. (1474-5488(Electronic)). 10.1016/S1470-2045(18)30354-1 29866475 29 Kumar S.K. …

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy.

Multiple myeloma (MM) is an incurable malignancy of plasma cells with a clinical course characterized by multiple relapses and treatment refractoriness. While recent treatment advancements have extended overall survival (OS), refractory MM has a poor prognosis, with a median OS of between 4 and 6 months. Nuclear export inhibition, specifically inhibition of CRM1/XPO1, is an emerging novel treatment modality that has shown promise in treatment-refractory MM. Initially discovered in yeast in 1983, early clinical applications were met with significant toxicities that limited their utility. The cr…