Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully demonstrated. In this study, we first investigated the correlation between aggrephagy signaling, MM immune microenvironment composition and disease prognosis. Single-cell RNA-seq data, including the expression profiles of 12,187 single cells from seven MM bone marrow (BM) and seven healthy BM samples, were analyzed by non-negative matrix factorization for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from the Gene Expression Omnibus database were used to evaluate the prognostic value of aggrephagy-related immune cell subtypes and predict immune checkpoint blockade immunotherapeutic response in MM. Compared with healthy BM, MM BM exhibited different patterns of aggrephagy-related gene expression. In MM BM, macrophages, CD8+ T cells, B cells and natural killer cells could be grouped into four to nine aggrephagy-related subclusters. The signature of aggrephagy signaling molecule expression in the immune cells correlates with the patient\'s prognosis. Our investigation provides a novel view of aggrephagy signaling in MM tumor microenvironment cells, which might be a prognostic indicator and potential target for MM treatment.

Non-secretory multiple myeloma (NSMM) is a rare cancer of plasma cells characterized by the absence of detectable monoclonal M protein in the blood or urine. A 57-year-old woman presented with mandibular pain but without intraoral swelling. Imaging studies revealed multiple osteolytic lesions in her mandible and pronounced root resorption of the left mandibular second molar. Biopsy results showed atypical plasmacytoid cells positive for anti-kappa, CD138, MUM1, and CD79a antibodies, but negative for anti-lambda and CD20. These results were indicative of a malignant plasma cell neoplasm. No abnormalities were revealed by free light chain assay or by serum or urine protein electrophoresis, leading to a diagnosis of NSMM. The patient began chemotherapy in conjunction with bisphosphonate therapy and achieved remission following treatment. This case underscores the critical role of dentists in the early detection and prevention of NSMM complications, as the disease can initially present in the oral cavity.

UNASSIGNED: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM.
UNASSIGNED: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO.
UNASSIGNED: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings.
UNASSIGNED: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer.
METHODS: In this study, interleukin-18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls.
RESULTS: Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001).
CONCLUSIONS: In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases.

Multiple myeloma (MM), mature B-cell lineage neoplasm, is characterized by abnormal clonal proliferation of plasma cells and presence of monoclonal protein (M protein). The study was conducted to reveal presenting features, laboratory findings, Eastern Cooperative Oncology Group (ECOG) performance status and skeletal survey on patients with multiple myeloma. This descriptive, cross-sectional study was carried out in the Department of Haematology, Dhaka Medical College Hospital, Dhaka, Bangladesh from January 2019 to July 2020 with a sample size of 81. Data were collected in a case record form after obtaining informed verbal consent from patients and /or their legal guardians. Relevant ethical issues and data quality assurance were taken into consideration. Data were analyzed with SPSS, Version 25.0 with presentation in figures and tables with frequency, percentage, mean and standard deviation based on data nature. Statistical tests were carried out as appropriate with 5.0% level of significance for assessing statistical association. Mean age of the patients was 58.9±12.0 years. Male female ratio was 2:1. 35(43.2%) patients were smokers with only 2(2.5%) had family history of haematological malignancies. Bone pain (72.8%) was the most common presenting feature, while hypertension (59.1%), diabetes mellitus (29.5%), respiratory illness (11.3%) and cardiac disease (11.4%) were the common co-morbidities. Most common ECOG performance status was ECOG-1(48.1%). Mean haemoglobin (Hb) was 9.4±2.3gm/dl and mean erythrocyte sedimentation rate (ESR) was 89.5±42.1 mm in 1st hour. Mean serum creatinine level was 2.0±1.85 mg/dl and ≥2.0mg/dl in 42(34.2%). Among 50 documentation serum lactate dehydrogenase (LDH) was raised in 18(36.0%). Mean serum calcium level was 9.6±1.8mg/dl >11.0mg/dL in 10(14.5%) cases. Serum albumin <3.5gm/dl in 37(49.3%), β2-microglobulin >5.5mg/dl in 37(57.8%) cases, International staging system (ISS) stage III was in 59.4% and Bence Jones Protein (BJP) was present in 46.7% cases. Lytic lesions were present in 75.0%, In 38(74.5%) patients vertebrae were involved, while in 18(35.2%) ribs were involved, in 14(27.5%) patients skull was involved and in 3(5.9%) patients involved bones were femur, humerus, sternum and scapula. Mean plasma cells percentage was 62.1±24.9%. Immuno-Fixation Electrophoresis (IFE) revealed IgG (72.7%), IgA (18.2%), Free light chain (FLC) (9.1%). FLC ratio was ≥100 in 29.0% cases. Significant statistical association was observed between serum creatinine with Hb concentration (p<0.05), serum creatinine level with ISS staging (p<0.05) and serum calcium level (p<0/05), while insignificant association was revealed between BJP present status and serum creatinine level (p>0.05). Bone pain, fatigue, fever and neurological impairment were the common presenting features. Anaemia, renal impairment and skeletal lytic events were the prominent physical findings. ISS staging was statistically associated with serum creatinine level, while serum calcium level was associated with serum creatinine and lytic lesions.

Multiple myeloma (MM) is a form of clonal plasma cell malignancy that associates with clinical manifestations such as anemia, hypercalcemia, bone pain, and renal impairment. Approximately 20-50% of MM patients at initial diagnosis experience renal injury, a vital complication that significantly influences prognosis and quality of life. This review seeks to clarify the multifaceted mechanisms of renal injury in MM, scrutinizing the pathogenic role of monoclonal proteins, the impact of hypercalcemia, and direct renal infiltration by plasma cells. Furthermore, it evaluates current diagnostic approaches, reviews management strategies, and highlights potential avenues for future research. By incorporating the latest scientific evidence and insights, this article aims to provide a comprehensive understanding of MM-associated renal impairment, offering a valuable resource for researchers and clinicians in handling this complex complication.

In the intricate landscape of multiple myeloma, a hematologic malignancy of plasma cells, bone disease presents a pivotal and often debilitating complication. The emergence of Chimeric Antigen Receptor T-cell (CAR-T) therapy has marked a pivotal shift in the therapeutic landscape, offering novel avenues for the management of MM, particularly for those with relapsed or refractory disease. This innovative treatment modality not only targets malignant cells with precision but also influences the bone microenvironment, presenting both challenges and opportunities in patient care. In this comprehensive review, we aim to examine the multifaceted aspects of bone disease in patients with multiple myeloma and concurrent CAR-T therapy, highlighting its clinical ramifications and the latest advancements in diagnostic modalities and therapeutic interventions. The article aims to synthesize current understanding of the interplay between myeloma cells, CAR-T cells, and the bone microenvironment in the context of current treatment strategies in this challenging and unique patient population.

BACKGROUND: Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy.
METHODS: A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva.
METHODS: Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions.
METHODS: The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy.
RESULTS: Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue.
CONCLUSIONS: MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.

Evidence on real-world clinical and economic outcomes in patients with multiple myeloma (MM) and renal impairment (RI) is limited in the United States. This retrospective study aimed to generate an updated comprehensive assessment of the clinical and economic outcomes of MM patients with RI using the Medicare research identifiable files data with Part D linkage, which might assist in assessing the total clinical and socioeconomic burden of these high-risk and challenging-to-treat patients. Treatment patterns and clinical and economic outcomes in first line (1L) to fourth line (4L) therapy were described in Medicare beneficiaries (2012 to 2018) for MM patients with RI (RI MM cohort). For reference purposes, information on a general cohort of MM patients was generated and reported to highlight the clinical and economic burden of RI. Since the goal was to describe the burden of these patients, this study was not designed as a comparison between the 2 cohorts. Compared with the general MM cohort (n = 13,573), RI MM patients (24.9%) presented high MM-associated comorbidities. In the RI MM cohort, bortezomib-dexamethasone (45.7%), bortezomib-lenalidomide (18.6%), lenalidomide (12.3%), and bortezomib-cyclophosphamide (12.1%) were the most prevalent regimens in 1L; carfilzomib and pomalidomide were mostly received in 3L to 4L; and daratumumab in 4L. Across 1L to 4L, the RI MM cohort presented shorter median real-world progression-free survival (1L: 12.9 and 16.4 months) and overall survival (1L: 31.1 and 46.8 months) and higher all-cause healthcare resource utilization (1L incidence rate of inpatient days: 12.1 and 7.8 per person per year) than the general MM cohort. In the RI MM cohort, the mean all-cause total cost increased from 1L to 4L ($14,549-$18,667 per person per month) and was higher than that of the general MM cohort. RI MM patients presented higher clinical and economic burdens across 1L to 4L than the general MM patients in real-world clinical practice.

OBJECTIVE: Fatty infiltration of skeletal muscle (Myosteatosis) is associated with increased frailty, decreased muscle and mobility function, which seems fairly prevalent in multiple myeloma (MM) patients. This study aimed to determine the prognostic value of myosteatosis assessed by CT for progression-free survival (PFS) and overall survival (OS).
METHODS: This IRB-approved cohort study included patients with newly diagnosed MM who were treated at a single university hospital and received CT at baseline. Geriatric assessment was performed via International Myeloma Working Group frailty score and Revised Myeloma Comorbidity Index. Myosteatosis was determined through measurement of paravertebral muscle radiodensity. Statistical analyses included uni- and multivariable Cox proportional hazard models and the Kaplan-Meier-method.
RESULTS: A total of 226 newly diagnosed MM patients (median age: 65 years [range: 29-89], 63% males, mean BMI: 25 [14-42]) were analyzed. The prevalence of myosteatosis was 51%. Muscle radiodensity was significantly decreased in individuals with International Staging System stage III vs. I (p < 0.001), indicating higher fatty muscle infiltration in patients with advanced disease. Both PFS and OS were significantly decreased in patients with myosteatosis (PFS: median 32.0 months (95% CI 20.5.5-42.2) vs. 66.4 months without myosteatosis (95% CI 42.5-not reached), p < .001); OS: median 58.6 (95% CI 51.3-90.2) vs. not reached, p < .001). Myosteatosis remained an independent predictor of OS in multivariable analyses (HR: 1.98; 95%-CI: 1.20-3.27).
CONCLUSIONS: Myosteatosis seems fairly prevalent in patients with newly diagnosed MM and associated with impaired overall survival. Prospective clinical trials are required to better understand the role of myosteatosis in MM patients.