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A phase II multi-arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma.

Magrolimab is a monoclonal antibody that blocks CD47, a 'do not eat me' signal overexpressed on tumor cells. CD47 is overexpressed in multiple myeloma (MM), which contributes to its pathogenesis. Preclinical studies have shown that CD47 blockade induces macrophage activation, resulting in elimination of myeloma cells, and that there is synergy between magrolimab and certain anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This phase II study investigates magrolimab in combination with commonly used myeloma therapies in patien…

Regulatory Effect and Mechanism of Erythroblastic Island Macrophages on Anemia in Patients with Newly Diagnosed Multiple Myeloma.

ObjectiveTo examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia.MethodsWe collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia.ResultsBased on the clinical characteristics of …

Primary gastric amyloidosis associated with linitis plastica and delayed progression to systemic amyloidosis and multiple myeloma.

We report the case of a woman in her 50s who underwent, 5 years prior, a total gastrectomy after neoadjuvant chemotherapy for diffuse-type gastric cancer diagnosed during a workup for isolated gastric primary light chain (AL) amyloidosis. At the time of diagnosis, immunoglobulins light chain measurements and bone marrow biopsy were performed to rule out multiple myeloma and came back normal. Three years later, the patient developed systemic amyloidosis involving the heart and the lungs, after which she developed multiple myeloma. Isolated amyloid deposits in the stomach are a rare finding. Whi…

Effectiveness of a vitamin D regimen in deficient multiple myeloma patients and its effect on peripheral neuropathy.

PurposePeripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D3 supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D3 regimen on achieving adequate vitamin D levels in deficient MM patients and to (2) exploratively evaluate the effect of vitamin D3 supplementation on PN.MethodsThirty-nine MM patients with inadequate (3 for 6 months according to a dose escalation regimen that consisted of on…

P57 PRE-EXPOSURE PROPHYLAXIS FOR COVID-19 WITH TIXAGEVIMAB/CILGAVIMAB (EVUSHELD) IN PATIENTS WITH MULTIPLE MYELOMA

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… Introduction: In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with severe clinical course and high mortality rates, due to the concomitant disease- and treatment-related immunosuppression. Furthermore, immune response to COVID-19 vaccination is attenuated. …

Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapy in Multiple Myeloma: Moving Into the Future.

Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective treatment options. However, the advent of chimeric antigen receptor (CAR) T-cell and T-cell redirecting bispecific antibody (BsAb) therapies has led to unprecedented response rates and durations of response in heavily relapsed/refractory (R/R) populations. Currently, two B-cell maturation antigen (BCMA)-directed CAR T-cell therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) as well as one BCMA/CD3 BsAb (teclistamab)…

Переход (iCT) к протеазонной ингибиторной терапии: общинный подход к управлению несколькими миеломами.

Долгосрочное протеиновое ингибиторное лечение (ПИ) может улучшить множественные результаты миэломы (ММ), однако это может быть трудно достичь в клинической практике из-за токсичности, комординации и бремени многократного родительского управления. США MM-6 (В тыс.NCT03173092) зачисленные пациенты, имеющие право на трансплантацию, с новым диагнозом MM для получения ixazomib-lenalidomide-dexamethasone (IRd); ≤39 циклы или до продвижения или токсичности) после three циклы впрыскивания на основе борцезомида. Первичная конечная точка: 2- годовое безподвижное выживание (ПМС). Ключевые вторичные/экспе

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Long-term proteasome inhibitor (PI) treatment can improve multiple myeloma (MM) outcomes, but this can be difficult to achieve in clinical practice due to toxicity, comorbidities, and the burden of repeated parenteral administration. US MM-6 (NCT03173092) enrolled transplant-ineligible patients with newly diagnosed MM to receive all-oral ixazomib-lenalidomid…

Neurobio-logy of multiple myeloma and its therapeutical use - results of the pilot study with a control arm.

BACKGROUND: Myeloma cells, occupying a bone marrow niche, are influenced not only by neighbouring stroma cells but also by signals from the axons of sympathetic nervous system. The nervous system is directly involved in the process of myeloma progression. Among other cancers, patients with myeloma suffer the most difficult distress generating intensive adrenergic signals, causing its further progression. There is a question arising from these facts regarding whether psychological interventions, modulating a function of the nervous system, can further improve outcomes of myeloma treatments. We

The unknown impact of multiple myeloma: assessing the impact of financial well-being on quality of life of caregivers.

PURPOSE: Patients with multiple myeloma and their caregivers are financially burdened, and their quality of life is significantly affected by treatment costs and care expenses. The aim of our study is to examine the impact of financial well-being of the caregiver on the life quality of patients with multiple myeloma. METHODS: The study included 113 patients with multiple myeloma and 113 caregivers in two hospitals located in Western Turkey. This study evaluated the demographic characteristics of patients and their caregivers, financial status, financial well-being, and quality of life of care…

High Hospital-related Costs at the End-of-life in Patients With Multiple Myeloma: A Single-center Study.

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… MM = multiple myeloma; ACT = anticancer treatment; ICU = intensive care unit; ED = emergency department. … MM = multiple myeloma; ACT = anticancer treatment; ICU = intensive care unit. This study aimed to contribute to the scarce research on end-of-life costs of hematological malignancies and particularly in MM. …

CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1.

Targeting nucleotide biosynthesis is a proven strategy for the treatment of cancer but is limited by toxicity, reflecting the fundamental nucleotide requirement of dividing cells. The rate limiting step in de novo pyrimidine synthesis is of interest, being catalyzed by two homologous enzymes, CTP synthase 1 (CTPS1) and CTPS2, that could be differentially targeted. Herein, analyses of publicly available datasets identified an essential role for CTPS1 in multiple myeloma (MM), linking high expression of CTPS1 (but not CTPS2) with advanced disease and poor outcomes. In cellular experiments, CTPS1…

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies.

With the continuous improvement in survival of cancer patients, including those with multiple myeloma, related to the novel treatment agents and therapeutic approaches, the probability for patients to develop cardiovascular disease has significantly increased, especially in elderly patients and those with additional risk factors. Multiple myeloma is indeed a disease of the elderly population and so these patients are, solely by age, at an increased risk of cardiovascular disease. Risk factors for these events can be patient-, disease- and/or therapy-related, and they have been shown to adverse…

Impact of second primary malignancy post-autologous transplantation on outcomes of multiple myeloma: a CIBMTR analysis.

The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progre…

Retinal Microvascular Changes in Patients with Multiple Myeloma: A Study Based on Optical Coherence Tomography Angiography.

Purpose: Ocular microvascular networks and variables were analyzed using optical coherence tomography angiography (OCTA) in patients with multiple myeloma (MM) who had no pathological findings in their routine ophthalmologic examinations.Methods: The study included 31 patients with a diagnosis of MM and 30 healthy controls. The ophthalmologic examination findings and OCTA measurements of the participants were prospectively analyzed. We evaluated the superficial capillary plexus (SCP) vessel density (VD) and deep capillary plexus (DCP) VD in macular region, radial peripapillary capillary (RPC) …

Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma.

Previous studies showed antitumor activity for plitidepsin plus dexamethasone (DXM) in relapsed/refractory multiple myeloma (r/r MM), and in vitro synergism with bortezomib (BTZ) or DXM against MM cells. This phase I trial evaluated plitidepsin (3-h intravenous infusion Day 1 and 15), BTZ (subcutaneous bolus Day 1, 4, 8, and 11), and DXM (orally Day 1, 8, 15, and 22), every 4 weeks in 36 r/r MM patients. Twenty-two patients were treated using a standard dose escalation design (10 at the recommended dose [RD] cohort), and 14 additional patients were treated to expand the RD cohort. No dose-limi…

Serum Levels of Interleukin-1β and Disease Progression in Multiple Myeloma Patients: A Case and Control Study.

OBJECTIVE: Multiple myeloma  (MM) is known as an incurable heterogeneous plasma cell malignancy that presents with a variety of clinical manifestations. Inflammation plays an important role in this disease. Cytokines and Chemokines cause the progression of the disease. One of them is interleukin-1β (IL-1β), which may be involved in the pathogenesis of MM. Other markers such as calcium, albumin, creatinine, globulins, and total protein are also used to diagnose and prognosis patients. The main purpose of this study was to evaluate the serum level of IL-1β and various forms of calcium (total cal…

Investigation of the frequency of bortezomib neuropathy in patients with multiple myeloma diagnosis with normal and abnormal genetic characteristics.

INTRODUCTION: Bortezomib-induced peripheral neuropathy in patients with multiple myeloma is an undesirable and sometimes severe side effect. Our study aimed to examine whether there was a difference in bortezomib-induced peripheral neuropathy between multiple myeloma patients with normal and abnormal genetic characteristics. METHODS: This retrospective analysis is based on the assessment of bortezomib-induced peripheral neuropathy frequency in newly-diagnosed multiple myeloma patients with normal (n = 68) and abnormal (n = 45) genetic profiles. A total of 113 patients diagnosed with multiple …

In-depth analysis of alternative splicing landscape in multiple myeloma and potential role of dysregulated splicing factors.

Splicing changes are common in cancer and are associated with dysregulated splicing factors. Here, we analyzed RNA-seq data from 323 newly diagnosed multiple myeloma (MM) patients and described the alternative splicing (AS) landscape. We observed a large number of splicing pattern changes in MM cells compared to normal plasma cells (NPC). The most common events were alterations of mutually exclusive exons and exon skipping. Most of these events were observed in the absence of overall changes in gene expression and often impacted the coding potential of the alternatively spliced genes. To under…

Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis.

Patients with multiple myeloma (MM) have a diminished immune response to coronavirus disease 2019 (COVID-19) vaccines. Risk factors for an impaired immune response are yet to be determined. We aimed to summarize the COVID-19 vaccine immunogenicity and to identify factors that influence the humoral immune response in patients with MM. Two reviewers independently conducted a literature search in MEDLINE, Embase, ISI Web of Science, Cochrane library, and Clinicaltrials.gov from existence until 24 May 24 2022. (PROSPERO: CRD42021277005). A total of 15 studies were included in the systematic review…

Clinical Characteristics and Prognosis of Multiple Myeloma With Myelomatous Pleural Effusion: A Retrospective Single-Center Study.

Objectives: Myelomatous pleural effusion is a rare presentation of extramedullary disease in multiple myeloma, which has been reported with dismal prognosis. We aimed to explore whether it has distinctive clinical characteristics and outcomes compared to other anatomic locations of extramedullary involvements. Methods: Multiple myeloma patients diagnosed at our institution from 2010 to 2020 were retrieved retrospectively. In total, 42 pairs of patients with and without extramedullary disease were enrolled, including 13 with myelomatous pleural effusion. The clinical and laboratory parameters w…