Current guidelines recommend [18F]FDG PET/CT as the preferred imaging modality for suspected extramedullary bone plasmacytomas, while whole-body magnetic resonance imaging (WB-MRI) is indicated for solitary bone plasmacytomas. Despite these recommendations, the available evidence comparing the diagnostic efficacy of both techniques remains limited. The aim of this study was to compare the diagnostic efficacy of WB-MRI and [18F]FDG PET/CT in the initial evaluation of plasmacytomas.

We performed a multicenter, observational, and retrospective analysis of patients diagnosed with plasmacytoma who underwent WB-MRI and/or [18F]FDG PET/CT as part of their diagnostic workup. Lesions identified were categorized by anatomic location, and concordance between WB-MRI and [18F]FDG PET/CT findings was assessed. The McNemar test and Pearson χ2 test were used to compare detection rates between WB-MRI and [18F]FDG PET/CT.

The study included 73 patients (33 men) recruited between 2012 and 2023, age range 30-94 years (mean 63.4 ± 12.2 y). Of these, 56 patients underwent both diagnostic tests. Diagnoses revealed solitary plasmacytoma in 16 patients, concurrent multiple myeloma (MM) and plasmacytoma in 18 patients, and plasmacytoma in 22 patients with a prior MM history. Out of the 56 plasmacytomas, 40 were osseous and 16 were extramedullary. WB-MRI detected 98.2% of plasmacytomas compared with 83.9% for [18F]FDG PET/CT, with a statistically significant difference of OR 9 (95% CI: 1.2-394.5), P=0.021. Concordance was very high for osseous plasmacytomas but moderate for extramedullary plasmacytomas.

These findings suggest WB-MRI is an alternative to [18F]FDG PET/CT for detecting plasmacytomas. A comprehensive clinical and radiologic assessment is essential for the optimal evaluation of patients with plasmacytoma.

Type I melanoma antigen gene proteins CT7 (MAGE-C1/CT7), a cancer-testis (CT) gene, correlated with clinical parameters at diagnosis of multiple myeloma (MM). We first analyzed single-cell ribonucleic acid sequencing data from public databases to evaluate the expression of MAGE-C1/CT7 in MM patients and showed that MAGE-C1/CT7 is highly and specifically expressed in the MM cells. We then interrogated data from 216 consecutive cases with MAGE-C1/CT7 transcripts by quantitative real-time polymerase chain reaction longitudinally monitored in our center. The positive rate of MAGE-C1/CT7 at baseline was 87.3%, with a median level of 4.46% (0.01-939.5). In univariate Cox regression analysis, peri-ASCT MAGE-C1/CT7 status showed better discriminatory ability in PFS and survival than peri-ASCT multi-parameter flow-cytometry status assessed by flow cytometry. In multivariate analysis, patients who were MAGE-C1/CT7-negative pre-transplant and posttransplant had significantly better PFS than those who were positive in both determinations (HR = 0.33, 95% CI: 0.14, 0.80, p = 0.01). In 69 patients with informative samples, we found a 2-log decrease in MAGE-C1/CT7 transcript concentration after the second induction cycle correlated with achieving negative MAGE-C1/CT7-test results both pre-transplant and posttransplant (OR = 6.08, 95% CI: 1.78, 20.74, p = 0.004). Our data showed the predictive value of peri-ASCT frontline treatment. A 2-log decrease of MAGE-C1/CT7 post-induction cycle 2 compared to baseline correlated with a negative peri-ASCT MAGE-C1/CT7 status, providing an earlier prognostic marker of treatment response.

Serum protein electrophoresis and serum free light chain (SFLC) assays are standard methods for monitoring patients with multiple myeloma (MM). However, patients with non-secretory MM often require invasive bone marrow biopsies to monitor treatment response and disease progression. Recently, serum soluble B-cell maturation antigen (sBCMA) has been proposed as an alternative biomarker for monitoring of MM, including non-secretory disease. We aimed to optimize the performance of and validate a serum sBCMA enzyme-linked immunosorbent assay (ELISA) from R&D Systems for research and eventual clinical use.

A total allowable error of 25 % was used, with one-third (8.3 %) budgeted for imprecision, one-third for bias, and one-half (12.5 %) as the allowable deviation from linearity. For imprecision, the repeatability coefficient of variation (CV) was acceptable, but the within-laboratory CV was not. We were limited in our ability to assess accuracy, but recovery of the ELISA standards was acceptable, and the sBCMA concentrations determined in various patient populations compared well to previous publications. The sBCMA concentration also correlated significantly with the M-protein concentration and the involved/uninvolved SFLC ratio. The sBCMA ELISA was verified to be linear within the allowable deviation between 99.04-1179.36 pg/mL. We attempted to confirm stability of serum sBCMA stored at room temperature, 4 °C, and -20 °C for up to 50 weeks, but the assay reproducibility was too poor for this to be assessed adequately.

Despite efforts to optimize the performance of the ELISA, the results were not reproducible enough over time to allow us to implement this sBCMA ELISA for clinical use.

Despite recent advances in the treatment of Waldenström macroglobulenimia (WM), including the development of Bruton tyrosine kinase inhibitors (BTKis), the disease remains incurable highlighting the urgent need for new treatments. The overexpression of BCL2 in WM cells promotes cell survival by resisting apoptosis and contributes to resistance to chemotherapy and targeted therapies. Concurrently, Bcl2 proteins that are encoded by oncogenes supporting cell survival are frequently upregulated in WM, even in the presence of DNA-damaging agents, and hence have emerged as an alternative therapeutic target. Venetoclax serves as a novel orally administered small agent that targets Bcl-2 protein by acting as a BCL2 homology domain 3 (BH3) mimetic and has shown promising results in WM patients, including those previously treated with BTKis. Furthermore, venetoclax, in combination with standard WM regimens, has shown enhanced activity, but further studies are required to elucidate the mechanism of its synergistic action and identify the patients who can benefit from the combined therapy. New BCL2 inhibitors are in advanced stages of clinical development and may offer additional options. The present review will focus on the current knowledge we have on BCL2 inhibitors in WM, the input of these compounds "from bench to bedside," and their utility in managing relapsed/refractory WM patients.

This study aimed to contribute to the literature by sharing experience of head-neck extramedullary plasmacytoma (EMP), which are rarely seen.

A total of 11 patients treated for head and neck region EMP between 2000 and 2023 were screened retrospectively.

The 11 patients comprised 9 men and 2 women with a mean age of 55.1 ± 16.2 (range, 16-74) years. The most affected regions were seen to be the sinonasal tract, larynx, and tonsils. In the histopathological examination, plasma cells had a mature or anaplastic appearance, and one of the kappa and lambda light chains was positive and the other was completely negative. The serum electrophoresis and bone marrow flow cytometry results were negative. Of the patients with confirmed EMP diagnosis, 8 were treated with radiotherapy (RT) alone, 1 patient with maxillectomy, and 1 patient endoscopic sinus surgery followed by RT. RT was applied at a dose of 44 to 50 Gy for 22 to 25 sessions. In 1 patient, RT and chemotherapy were applied together.

In cases presenting with a submucosal, destructive tumor in the head and neck region, especially in the sinonasal region, EMP should be kept in mind. When histopathological results are confirmed, a differential diagnosis from multiple myeloma (MM) is required. Flow cytometry is of guidance in the differentiation of EMP from extranodal lymphoma. However, it should be noted that the effect of RT may be less in EMPs originating from the paranasal sinus compared with other anatomic regions, and surgery may be required before or after RT. A radiation dose of 45 Gy is sufficient for local control. Patients require long-term follow-up, as there is a possibility of EMP transforming to MM.

Dynamic quantification of monoclonal immunoglobulin proteins (M-proteins) by immunotyping using immunosubtraction (ISUB) through capillary zone electrophoresis (CZE) was performed to examine the efficacy of chemotherapy drugs in patients with multiple myeloma (MM). Twenty-one patients with eight different types of M-protein were analyzed, and M-protein quantification during chemotherapy regimens was dynamically monitored. For patients with M-protein identified by CZE, immunotyping by ISUB can accurately determine the percentage of M-protein. In this study, 15 of the 16 included patients with a definite diagnosis of MM were initially treated with bortezomib chemotherapy, and the treatment efficacy differed significantly among individuals. Three patients showed M-protein clearance, with the M-protein decreasing by more than 50% after the first course of treatment. Capillary-based immunotyping accurately determined the percentage of M-proteins. Dynamic monitoring of M-protein through immunotyping using ISUB can objectively and effectively aid in evaluating treatment efficacy. Clinically, chemotherapeutic drugs that reduce M-protein levels by more than 50% after a treatment course should be selected. The early detection of trace changes in M-protein levels is crucial for disease monitoring and medication guidance. Quantification of M-protein should be regularly undertaken in patients with MM.

The International Myeloma Working Group (IMWG) defines myeloma related bone disease (MBD) as a diagnostic criterion for symptomatic multiple myeloma (MM) as the presence of osteolytic lesions ≥ 5 mm or more than one focal lesion (FL) ≥ 5 mm by magnetic resonance imaging (MRI). Whole-body low-dose CT (WBLDCT) is recommended as the first-choice imaging technique for the diagnosis of MBD with 18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG-PET/CT) being considered a possible alternative at staging, whereas use of MRI studies is recommended in cases without myeloma-defining events (MDEs) in order to exclude the presence of FLs. Furthermore, use of 18F-FDG-PET/CT is recommended in response assessment, to be integrated with hematologic response and bone marrow minimal residual disease (MRD).

In this paper, we review novel functional imaging techniques in MM, particularly focusing on their advantages, limits, applications and comparisons with 18F-FDG-PET/CT or other standardized imaging techniques.

Combining both morphological and functional imaging, 18F-FDG-PET/CT is currently considered a standard imaging technique in MM for staging (despite false positive or negative results) and response assessment. The introduction of novel functional imaging techniques, as whole-body diffusion-weighted magnetic resonance imaging (WB-DWI-MRI), or novel PET tracers might be useful in overcoming these limits. Future studies will give more information on the complementarity of these imaging techniques or whether one of them might become a new gold standard in MM.

Systemic light-chain amyloidosis (AL) is an acquired protein misfolding disease characterized by deposition of immunoglobulin light-chain fibrils most often secreted from clonal plasma cells. In this retrospective study we analyzed the impact of iFISH aberrations on clinical characteristics and outcomes in 175 AL patients presented between 2015 and 2024. The most common aberrations were t(11;14) (57%), deletion 13q14 (33%), +1q21 (21%), hyperdiploidy (21%) and deletion 16q23 (17%). Significant elevations in dFLC levels were observed in patients with + 1q21 (median 407 vs. 213 mg/l, p = 0.04) and deletion 16q23 (median 476 vs. 204, p = 0.006). Only + 1q21 was associated with increased levels of cardiac biomarkers NTproBNP (median 9945 vs. 3538 pg/ml, p = 0.002) and hsTnT (median 110 vs. 53 ng/l, p = 0.002). This resulted in an increased proportion of patients with Mayo stage IIIb (53% vs. 26%, p = 0.01). Patients with + 1q21 had more advanced plasma cell disease (p = 0.0004). Our study highlights for the first time + 1q21 as the key aberration associated with advanced cardiac and plasma cell disease. After 17 months of follow-up, overall survival was significantly worse in patients with + 1q21 treated with daratumumab (7.2 months vs. not reached, p = 0.006). Alternative therapeutic approaches such as CAR-T therapies or bispecific antibodies should be further investigated.

This study aims to perform a bibliometric visual analysis and bioinformatics analysis to explore the research hotspots and trends of renal impairment in multiple myeloma, including the associated genes and signal pathways over the past two decades.

The Web of Science Core Collection database was utilized as the data source to retrieve literature on renal impairment in multiple myeloma from 2000 to 2023. The selected literature was analyzed using bibliometric and bioinformatics software, including Bibliometrix, VOSviewer 1.6.16, Citespace 5.7R5 and Cytoscape 3.7.1 software.

This study encompassed 2152 articles that were published from 2000 to 2023, demonstrating an overall upward trend in annual publications and citations. Among the set of 27 core journals examined, the "CUREUS JOURNAL OF MEDICAL SCIENCE" exhibited the highest frequency of publications, while "BLOOD" emerged as the most frequently cited source. The global research on renal impairment in multiple myeloma research included contributions from 84 countries/regions, with the United States leading in terms of publication output and Mayo Clinic playing a central role in fostering inter-agency collaboration. Keywords such as "daratumumab", "carfilzomib", "diagnostic criteria" and "kidney biopsy" included recent research hotspots. We hypothesized that the TP53, AKT1, MYC, and CTNNB1 genes were involved in epithelial cell proliferation and the positive regulation of the MAPK cascade through signaling receptor activator activity, receptor-ligand interactions, and cytokine receptor binding. Simultaneously, they were implicated in renal impairment in multiple myeloma via the PI3K/Akt and MAPK signaling pathways.

This research employed bibliometric visual analysis and bioinformatics analysis to identify the current focus and future directions of studying renal impairment in multiple myeloma, as well as to explore the associated genes and signaling pathways. The management of renal impairment in patients with multiple myeloma has a significant impact on medical costs. Clinical physicians need to consider how to allocate medical resources reasonably, ensure that patients can receive necessary diagnosis and treatment, and explore cost-effective treatment options. The management of these patients requires interdisciplinary medical services, which should integrate basic and clinical research, especially the development of new treatment plans, to improve patients' quality of life and guide future treatment choices.

Serum protein electrophoresis interpretation requires a substantial amount of manual work. In 2020, Chabrun et al. created a machine learning method called SPECTR for the task. We aimed to validate and test the SPECTR method against our results of more precise immunofixation electrophoresis.

We gathered 34 625 patients and their first serum protein electrophoresis sample in Helsinki University Hospital. We trained three neural network models: (1) a fractionation model to fractionate electropherograms; (2) a classification model to classify samples to normal, ambiguous, and abnormal (i.e. containing paraprotein); (3) an integration model to predict concentration and location of paraproteins.

The fractionation model demonstrated an error rate of ≤0.33 g/L in 95 % samples. The classification model achieved an area under the curve of 97 % in receiver operating characteristic analysis. The integration model demonstrated a coefficient of determination (R2) of 0.991 and a root-mean-square error of 1.37 g/L in linear regression.

The neural network models proved to be suitable for partial automation in serum protein electrophoresis reporting, i.e. classification of normal electropherograms. Furthermore, the models can accurately suggest the location and concentration of paraproteins.

In 2014, the International Myeloma Working Group (IMWG) updated the criteria for diagnosing myeloma and added three additional criteria to the traditional Calcium elevation, Renal impairment, Anemia, Bone disease (CRAB) criteria, called the Sixty % marrow plama cells, Light chain ratio >60, Mri demonstates lytic lesions (SLiM) criteria (clonal bone marrow plasma cells ≥60%, involved to uninvolved free light chain ratio (FLCr) ≥100 and >1 focal lesion on magnetic resonance imaging (MRI)). We report on the outcomes of 30 patients who underwent autologous stem cell transplantation (ASCT) where therapy was initiated solely based on SLiM criteria and compared them to a matched cohort of 60 patients whose myeloma-defining event was CRAB. The SLiM cohort had a shorter median time to neutrophil (15 vs. 16 days, p = 0.049) and platelet (15 vs. 17 days, p = 0.0004) engraftment. The 36-month overall survival (OS) was 100% in the SLiM group and 93.27% in the control group (95% CI 83.06%-97.42%), with a trend towards longer OS in the SLiM cohort (p = 0.065). The 36-month progression-free survival (PFS) was 91.61% in the SLiM (95% CI 69.93%-97.87%) and 65.95% in the control group (95% CI 52.31%-76.53%). There was no difference in the PFS between the cohorts (p = 0.414). ASCT is efficacious and safe in MM patients transplanted only due to SLIM criteria. Early intervention in this asymptomatic cohort did not appear to result in deeper responses or better PFS compared to outcomes in symptomatic patients.

Paraproteinemic neuropathies represent an important subset of peripheral neuropathies. Once identified, further evaluation into the paraproteinemic subtype, clinical exam pattern, and electrodiagnostic phenotype helps clarify if the paraproteinemia is coincidental or causal of the neuropathy, as not all paraproteinemias cause neuropathy. Of all paraproteinemias, immunoglobulin M (IgM)-associated peripheral neuropathy, or IgM neuropathy, is of particular importance as half of IgM neuropathies also harbor anti-myelin-associated glycoprotein antibodies, which produce a characteristic demyelinating pattern on nerve conduction testing. Immunoglobulin G and immunoglobulin A paraproteinemias are less strongly associated with peripheral neuropathy, except in the setting of multiple myeloma or osteosclerotic myeloma (POEMS syndrome), which have characteristic systemic features. In multiple myeloma, chemotherapy is more likely to result in neuropathy than the myeloma itself. Finally, the presence of systemic features (e.g., cardiomyopathy, nephropathy, recurrent carpal tunnel syndrome, and autonomic insufficiency) should raise concern for hereditary or acquired light (AL) chain amyloidosis. AL amyloidosis can occur in the setting of any light or heavy chain paraproteinemia. Central to the proper evaluation of paraproteinemic neuropathy is electrodiagnostic testing, which helps delineate axonal versus demyelinating paraproteinemic neuropathy, the latter often misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy.

An autologous stem cell transplant (ASCT) is the standard of care for eligible patients with multiple myeloma (MM). However, the success of ASCT largely hinges on efficient mobilization; thus, a thorough analysis of factors that may affect mobilization is essential.

The study consists of a single-center, retrospective chart review of 292 adult patients undergoing their first or second autologous transplantation for MM from 2016 to 2023. Patient demographics, serum lab values at the pre-collection evaluation visit, total stem cell capture (TC) in CD34/kg × 106 stem cell capture on the first day of apheresis (FC) in CD34/kg × 106, and the total number of days of apheresis (DOA) were retrieved from the electronic medical record (EMR).

Individuals with high folate levels experienced less DOA (1.43 ± 0.61) compared to those with normal folate levels (1.68 ± 0.82, p = 0.013). The high-folate group had a greater FC (3.26 ± 1.07) compared to the normal-folate group (2.88 ± 1.13, p = 0.013). High ferritin levels were associated with more DOA (1.79 ± 0.89) compared to the normal-ferritin group (1.51 ± 0.67, p = 0.034). Moderate anemia was significantly associated with decreased FC (p = 0.023) and increased DOA (p = 0.030). Abnormal hemoglobin (Hgb), ferritin, and folate statuses did not exhibit significant differences in survival analysis.

The findings reveal that folate, ferritin, and Hgb levels are significantly associated with apheresis outcomes, offering guidance for optimizing stem cell mobilization in patients with MM.

Multiple myeloma (MM) predominantly affects elderly individuals, but studies on older patients with MM are limited. The clinical characteristics and survival outcomes of patients with MM aged 80 years or over were retrospectively analyzed.

This retrospective multicenter study was conducted to investigate the clinical characteristics, treatment patterns, and survival outcomes of patients aged 80 years or over who were newly diagnosed with MM at five academic hospitals in Daegu, Korea, between 2010 and 2019.

A total of 127 patients with a median age of 83 years (range, 80-93 yr) were enrolled: 52 (40.9%) with Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, 84 (66.1%) with International Staging System (ISS) stage III disease, and 93 (73.2%) with a Charlson comorbidity index (CCI) > 4. Chemotherapy was administered to 86 patients (67.7%). The median overall survival was 9.3 months. Overall survival was significantly associated with ECOG PS > 2 (HR 2.26, 95% CI 1.43-3.59), ISS stage III (HR 1.99, 95% CI 1.18-3.34), and chemotherapy (HR 0.34, 95% CI 0.21-0.55). There was no statistically significant difference in event-free survival according to the type of anti-myeloma chemotherapy administered. The early mortality (EM) rate was 28.3%.

Even in patients with MM aged 80 years or over, chemotherapy can result in better survival outcomes than supportive care. Patients aged ≥ 80 years should not be excluded from chemotherapy based on age alone. However, reducing EM in elderly patients with newly diagnosed MM remains challenging.

This study aimed at describing the demographic and clinical characteristics, treatment patterns and overall survival of patients with MM in Brazil to identify gaps in the disease diagnosis and treatment.

MMyBRAve (NCT03506386) was a multicenter, observational study of patients diagnosed with MM in Brazil between January 2008 and December 2016, with data collection between August 2018 and September 2019 at 17 participating centers.

Of 943 patients included, 914 had complete data for overall survival (OS) analysis. The most used frontline regimens were cyclophosphamide, thalidomide and dexamethasone; bortezomib, cyclophosphamide and dexamethasone; and thalidomide and dexamethasone. After a median follow-up of 63 months, the median OS from diagnosis was 70 months. These results indicate continuous improvements in comparison with previous observational studies from Brazil. The median OS in transplantation-ineligible (N = 491) and eligible (N = 452) patients were 49 and 93 months, respectively (hazard ratio [HR] = 0.52; 95% confidence interval [CI], 0.43 to 0.63; P < .001). The median OS also differed between patients with and without known prognostic factors.

Despite the improvements, our results suggest that access to novel agents and transplantation continue to hinder further progress in patient outcomes in Brazil and countries with similar health-care constraints.

Abdominal multiple extramedullary plasmacytoma (EMP) is a rare disease. CD38-negative relapsed/refractory EMP after treatment with daratumumab has never been reported. In 2020, a patient with jaundice was diagnosed with plasmacytoma in another hospital, which progressed one year after receiving multiline therapy. In July 2021, he was admitted to our hospital and showed CD38-pogative plasmacytoma. The patient received 2 cycles of treatment including daratumumab, venetoclax and DCEP chemotherapy and achieved partial remission. However, he developed ascites and eventually died. Our case indicated that multiple EMP has much lower incidence and far worse prognosis than solitary EMP.

Multiple myeloma is an incurable plasma cell malignancy that evolves over decades through the selection and malignant transformation of monoclonal plasma cells. The evolution from precursor states to symptomatic disease is characterized by an increasing complexity of genomic alterations within the plasma cells and a remodelling of the microenvironment towards an immunosuppressive state. Notably, in patients with advanced disease, similar mechanisms of tumour escape and immune dysfunction mediate resistance to modern T cell-based therapies, such as T cell-engaging bispecific antibodies and chimeric antigen receptor (CAR)-T cells. Thus, an increasing number of clinical trials are assessing the efficiency and safety of these therapies in individuals with newly diagnosed multiple myeloma and high-risk smoldering multiple myeloma. In this Review, we summarize the current knowledge about tumour intrinsic and extrinsic processes underlying progression from precursor states to symptomatic myeloma and discuss the rationale for early interception including the use of T cell-redirecting therapies.

No specific description of monoclonal gammopathies of undetermined significance (MGUS)-associated angioedema due to acquired C1 inhibitor deficiency (AAE-C1-INH) has been reported yet.

To describe the biological and clinical characteristics, evolution, and response to treatment of MGUS-associated AAE-C1-INH.

We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period.

Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included; 68% displayed anti-C1-INH antibodies. The monoclonal component was an IgM in 24 patients, IgG in 11, and IgA in 6 patients. The mean age at first angioedema attack was 63 years (standard deviation [SD] = 13 years) and at diagnosis 66 years (SD = 11 years). A total of 88% patients benefited from acute attack treatments, and 77% from long-term prophylaxis, either danazol, tranexamic acid, or lanadelumab. Median follow-up was 7 years, during which 14 patients (33%) evolved into well-defined malignant hemopathies. Fifty percent of patients were given a hematological treatment, either rituximab alone, indicated by recurrent attacks of angioedema in patients with AAE-C1-INH with anti-C1-INH antibodies, or validated combinations of chemotherapies, indicated by evolution into a lymphoma in 7 patients and a myeloma in 3 patients. Fifteen patients (35%) were in clinical complete remission of angioedema at last visit, of whom 60% had an undetectable serum monoclonal immunoglobulin.

Complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy, as defined by an undetectable serum monoclonal immunoglobulin. In our MGUS-associated acquired angioedema cohort, we recorded an incidence of evolution into hematological malignancy of 4% per patient-year. It is therefore crucial to conduct full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attack frequency increases.

Multiple Myeloma (MM) is a hematological malignancy affecting bone marrow, most frequently in elderly men. Imaging has a crucial role in this disease. Recently, whole-body MRI has been introduced and it has gained growing interest due to is high sensitivity and specificity in evaluating bone marrow involvement in MM. Diffusion-weighted sequences (DWI) with apparent diffusion coefficient (ADC) maps have emerged as the most sensitive technique to evaluate patients with MM, both in the pre- and post-treatment setting. Aim of this review is to provide an overview of the role and main imaging findings of whole-body MRI in MM.

The objective of the study was to assess the prevalence of osteoporosis in patients with monoclonal gammopathy of undetermined significance (MGUS) and to determine the associated factors.

We conducted a case-control study, between January 2019 and April 2019, including patients with MGUS and age- and sex-matched healthy controls (one patient/three controls). For all participants, demographic and clinical data were collected as results of bone mineral density by two-photon X-ray absorptiometry at the lumbar spine and femoral neck.

In our series, we included 120 participants: 30 patients with MGUS and 90 healthy controls. In the MGUS carrier group, the mean age was 66.26 ± 8.61 years. The mean monoclonal peak was 11.57 g/L. Densitometric osteoporosis was noted in 12 (40%) patients with MGUS versus 17 (18.9%) in the control group (P = 0.021). In addition, only one patient with MGUS had a vertebral fracture. On multivariate analysis, associated factors with osteoporosis in the MGUS group were age (odds ratio [OR] = 1.14; confidence interval [CI] [1.03-1.26]; P < 0.05) and previous fracture (OR = 3.03; CI [1.22-15.06]; P < 0.05).

Our study suggests an increased risk of osteoporosis in patients with MGUS.

Studies on the prognosis of hepatitis B virus (HBV) reactivation following modern therapies for newly diagnosed MM (NDMM) are lacking. In this retrospective study, we aimed to assess the incidence, risk factors and prognosis of HBV reactivation in NDMM. A total of 33 of 355 patients with NDMM and HBV reactivation were included in this study. Multivariable analysis showed that hepatitis B surface antigen-positivity, hepatitis B core antibody-positivity, bortezomib-containing regimens, autologous stem cell transplantation, and gain of 1q21 were identified as independent risk factors of HBV reactivation in NDMM patients. The NDMM patients with HBV reactivation had poorer 3-year overall survival (OS) and progression-free survival (PFS) than did those without HBV reactivation, as confirmed by multivariate analysis. In conclusion, HBV reactivation in patients with NDMM constitutes a significant complication, correlating with reduced OS and PFS, and emerges as a potential adverse prognostic factor in the contemporary era of treatment.

Detecting monoclonal protein (M-protein), a hallmark of plasma cell disorders, traditionally relies on methods such as protein electrophoresis, immune-electrophoresis, and immunofixation electrophoresis (IFE). Mass spectrometry (MS)-based methods, such as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization-quadrupole time-of-flight (ESI-qTOF) MS, have emerged as sensitive methods. We explored the M-protein-detection efficacies of different MS techniques.

To isolate immunoglobulin and light chain proteins, six types of beads (IgG, IgA, IgM, kappa, lambda, and mixed kappa and lambda) were used to prepare samples along with CaptureSelect nanobody affinity beads (NBs). After purification, both MALDI-TOF MS and liquid chromatography coupled with Synapt G2 ESI-qTOF high-resolution MS analysis were performed. We purified 25 normal and 25 abnormal IFE samples using NBs and MALDI-TOF MS (NB-MALDI-TOF).

Abnormal samples showed monoclonal peaks, whereas normal samples showed polyclonal peaks. The IgG and mixed kappa and lambda beads showed monoclonal peaks following the use of daratumumab (an IgG/kappa type of monoclonal antibody) with both MALDI-TOF and ESI-qTOF MS analysis. The limits of detection for MALDI-TOF MS and ESI-qTOF MS were established as 0.1 g/dL and 0.025 g/dL, respectively. NB-MALDI-TOF and IFE exhibited comparable sensitivity and specificity (92% and 92%, respectively).

NBs for M-protein detection, particularly with mixed kappa-lambda beads, identified monoclonal peaks with both MALDI-TOF and ESI-qTOF analyses. Qualitative analysis using MALDI-TOF yielded results comparable with that of IFE. NB-MALDI-TOF might be used as an alternative method to replace conventional tests (such as IFE) to detect M-protein with high sensitivity.

Despite the development of novel drugs and the widespread use of hematopoietic cell transplantation, the prognosis of patients (pts) with multiple myeloma and extramedullary involvement (soft-tissue plasmacytoma, STP) is rather unfavorable.

A retrospective analysis of 120 pts with STP treated between 2007 and 2022 was performed. The effects of demographic and clinical characteristics on treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated.

The rate of serological response to first-line STP treatment (at least partial remission) was 67%, and the rate of imaging response was 59%. With a median follow-up of 84.2 months, the median PFS was 10.5 months (primary STP: 20.2 months; secondary STP: 5.8 months), and the median OS was 24.5 months (primary STP: 34.5 months; secondary STP: 12.4 months). Based on the multivariate regression analysis, secondary STP (HRPFS 2.75; HROS 2.63) and organ involvement (HRPFS 1.45; HROS 1.68) were found to be negative prognostic factors of both PFS and OS. In a prognostic model, pts with at least one of these factors had a significantly worse PFS (HRPFS 3.31) and OS (HROS 3.45) than those with none risk factor.

In pts with STP, risk-adapted treatment strategies including immunotherapies and cell therapies are urgently required.

Background/Objectives: Monoclonal gammopathies, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), are conditions marked by the overproduction of specific monoclonal proteins. Patients with these conditions are known to have a higher risk of fractures compared to the general population, yet there are no established guidelines for assessing or managing their skeletal health. The Trabecular Bone Score (TBS), which can be calculated from DXA images of the lumbar spine, provides additional insights into bone microarchitecture. Methods: This study aimed to determine whether TBS can serve as a supplementary tool in assessing bone loss in MGUS and SMM patients. Conducted from 2020 to 2023, the study involved 148 participants-74 diagnosed with a myeloma precursor state and 74 healthy controls-who underwent simultaneous DXA and TBS measurements. Results: The results indicated a weak positive correlation (R = 0.405) between DXA and TBS T-scores, suggesting that other factors may influence the measurements. When analyzed separately, the correlations remained weak for both MGUS (R = 0.250) and SMM (R = 0.485). Interestingly, discrepancies were noted in T-score classifications; for instance, a patient classified as normal via DXA could be deemed osteopenic or osteoporotic with TBS. Conclusions: Overall, the findings suggest that incorporating TBS alongside DXA can enhance the accuracy of bone density assessments, facilitating earlier diagnosis and treatment initiation for osteoporosis in asymptomatic patients with monoclonal gammopathies.

The aim of this study was to evaluate the impact of trabecular attenuation of the L1 vertebral body in low-dose CT in adult patients with multiple myeloma (MM), smoldering multiple myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS).

The study population consisted of 22 patients with MGUS and 51 consecutive patients with newly diagnosed MM (SMM, n = 21; symptomatic MM, n = 36). CT scans were conducted using a 128-slice CT scanner (Somatom go.Top, Siemens, Munich, Germany). Low-dose whole-body CT scans were performed at a single time point for each patient. Trabecular bone density values were obtained by defining regions of interest on non-contrast images at the level of L1 vertebra. A threshold of p = 0.05 was applied to determine statistical significance.

The median Hounsfield unit (HU) value in patients with MGUS, SMM, and MM was 148 HU (range 81-190), 130 HU (range 93-193), and 92 HU (range 26-190), respectively, with a statistically significant difference between the groups (p = 0.0015). Patients with HU values ≤ 92 had lower progression-free survival with statistically significant differences compared to the group with HU values > 92 (p < 0.0499).

This is the earliest evidence of the importance of evaluating L1 attenuation values in low-dose CT images in patients with MGUS, SMM, and MM. Further prospective studies could contribute to reinforcing these results and exploring the clinical applicability and generalization of L1 attenuation values in low-dose whole-body CT scans in routine clinical practice.

Many clinical trials of therapeutic interventions for multiple myeloma do not use patient important outcomes and rely on the use of surrogate endpoints. The aim of this systematic review was to depict the landscape of randomized controlled trials in myeloma research and compile the endpoints utilized.

We searched Embase, PubMed, and the Cochrane Library for randomized controlled trials in myeloma published in English up to October 2023. We included trials exploring efficacy of therapeutic modalities for myeloma itself or supportive care interventions.

A total of 2181 records, reporting data from 624 trials (448 comparing anti-myeloma treatments and 176 comparing supportive interventions) were deemed eligible. The most common primary outcome reported was disease response, followed by progression free survival (PFS) and overall survival (OS). Across all trials, 119 (19.1 %) used OS as the primary endpoint, while 316 (50.6 %) listed it as a secondary endpoint. Quality of life was less commonly prioritized, featured as primary endpoint only in seven studies (1.1 %) and as secondary endpoint in 115 studies (18.4 %). Studies funded by the pharmaceutical industry were more likely (Odds Ratio [OR] 3.85, 95 % CI 2.41-6.35) to use PFS as primary outcome. Similarly, studies with authors that had conflicts of interest with the funding source were more likely (OR 4.57, 95 % CI 2.72-7.92) to use PFS as the primary outcome.

While randomized controlled trials for multiple myeloma predominantly rely on surrogate endpoints, particularly PFS, the importance of OS as an outcome should not be overlooked.

A decade after International Myeloma Working Group (IMWG) biomarkers (SLiM criteria) were introduced, this real-world study examined their impact on diagnosis, therapy and outcomes in myeloma. Using the ANZ MRDR, 3489 newly diagnosed patients from 2013 to 2023, comprising 3232 diagnosed by CRAB ('CRAB patients', including 1758 who also satisfied ≥1 SLiM criteria) and 257 by SLiM ('SLiM patients') criteria were analysed. CRAB patients had higher R-ISS and lower performance status, with no difference in cytogenetic risk. SLiM patients had improved progression-free survival (PFS, 37.5 vs. 32.2 months, hazard ratio [HR] 1.31 [1.08-1.59], p = 0.003), overall survival (80.9 vs. 73.2 months, HR 1.64 [1.26-2.13], p < 0.001) and PFS2 (54.6 vs. 40.3 months, HR 1.51 [1.22-1.86], p < 0.001) compared with CRAB patients, partially explained by earlier diagnosis, with no differential impact between the plasma cell and light-chain criteria on PFS. However, 34% of CRAB patients did not manifest SLiM characteristics, raising the possibility that SLiM features are associated with different biological behaviours contributing to a better prognosis, for example, improved PFS2 in SLiM patients suggested less disease resistance at first relapse. These data support earlier initiation of therapy by SLiM. The superior survival outcomes of SLiM versus CRAB patients highlight the importance of defining these subgroups when interpreting therapeutic outcomes at induction and first relapse.

Monoclonal proteins are common, with a prevalence in the United States around 5% and the incidence increases with age. Although most patients are asymptomatic, the vast majority of cases are caused by a clonal plasma cell disorder. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions with variable risk of progression to multiple myeloma (MM). In recent years, significant progress has been made to better understand the factors that lead to the development of symptoms and progression to myeloma. In this review, we summarize the current diagnosis treatment guidelines for MGUS and SMM and highlight recent advances that underscore a shifting paradigm in the evaluation and management of plasma cell precursor conditions.

Background: Data on the outcome of octogenarian multiple myeloma (MM) patients (pts), especially if treated outside clinical studies, are scanty. Aims and Methods: MM pts ≥ 80 years, treated at TASMC with first-line therapy between 2010 and 2023, were reviewed. Characteristics and outcomes were analyzed. Results: A total number of 101 pts, of whom 54 were males with a median age of 84 years (80-98), were included. Among them, 67.4% had a Charlson comorbidity index of ≥5, 37% had ISS-3 (International staging system) and 20% had Revised-ISS-3. In our study, 44.5% received doublets and 50.5% received triplets/quadruplets. A bortezomib-based regimen was applied in 87%, and IMiDs were used in 27.7%. Despite an upfront employment of a low lenalidomide dose, dose reductions were required in 48%. Grade ≥ 3 adverse events (AEs) (mainly infections) were documented in 36.6% of patients, including grade 5 events in 9%, all attributed to infections. The overall response rate was 69%, including 31% ≥ VGPRs (Very good partial response). Sixty-seven percent (67%) received second-line therapy, administered within a median period of 12 months (1-84). Within a median follow-up period of 36 m (1-141), the median overall survival (OS) approached 42 m (range: 1-141); being shorter in pts > 84 years (HR = 1.7, p = 0.03), pts with lung disease (HR = 1.8, p = 0.044) and pts with ISS = 3 and R-ISS = 3 (HR = 1.65, p = 0.0016 and HR = 2.45, p = 0.006, respectively); Conclusions: Octogenarians treated outside clinical studies often have a lower tolerance to treatment. Nevertheless, upfront administration of low doses of anti-MM agents provided a response in the majority of patients, translated into impressive OS. Nevertheless, mortality due to AEs was high, emphasizing the need for new, "octogenarian-oriented" treatment protocols.

Multiple myeloma, a complex hematologic malignancy, has devastating consequences for patients, including dramatic bone loss, severe bone pain, and pathological fractures that markedly decrease the quality of life and impact the survival of affected patients. This necessitates a refined understanding of biomarkers for accurate diagnosis and prognosis of such severe malignancy. Therefore, this article comprehensively covers current research, elucidating the diverse spectrum of biomarkers employed in clinical settings. From traditional serum markers to advanced molecular profiling techniques, the review provides a thorough examination of their utility and limitations. Through this scoping review, emphasis is placed on the evolving landscape of personalized medicine, where biomarkers play a pivotal role in tailoring therapeutic strategies. The integration of genomic, proteomic, next generation sequencing and flow cytometric data further enriches the discussion, unravelling the molecular intricacies underlying disease progression. The updated criteria allow for the treatment of people who clearly would benefit from therapy and might live longer if treated before significant organ damage occurs. Navigating through the evolving diagnostic and prognostic paradigms in multiple myeloma, this article equips clinicians and researchers with crucial insights for optimizing patient care and advancing future therapeutic approaches.

Plasmacytomas are malignant tumours characterised by abnormal monoclonal proliferation of plasma cells. They may be osseous or may arise from soft tissues. Extramedullary plasmacytoma (EMP) accounts for only 1% of all head and neck malignancies. Septal plasmacytomas are extremely rare. Here, we report a case of an 80-year-old male patient with alocalised plasmacytoma arising from the nasal septum, which was resected endoscopically, with post-op radiotherapy and no recurrence in 1 year of follow-up. A multidisciplinary approach is required for the optimal diagnosis and management. It is essential to exclude any systemic involvement before arriving at a diagnosis of solitary plasmacytoma. Depending on lesion resectability, a combined therapy is the treatment of choice.

Rheumatic diseases were previously associated with increased incidence of monoclonal gammopathy (MG) and its malignant transformation. The present study aimed to investigate the prevalence, malignant transformation risk, clinical correlates and prognostic impact of MG in SLE.

A retrospective cohort study based on the medical records of n=1039 patients with SLE fulfilling the 1997 American College of Rheumatology (ACR), the 2019 European Alliance of Associations for Rheumatology (EULAR)/ACR and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria managed at two tertiary care departments of the University Hospital (Krakow, Poland) from January 2012 until November 2019.

SLE+MG cases were older at SLE diagnosis compared with non-MG SLE controls (53±15 years vs 37±15 years, respectively, p<0.01), had higher rates of lymphopenia, anaemia, haemolysis, serous effusions and interstitial lung disease (all p<0.05), and were more frequently treated with cyclophosphamide (57% vs 28%, p<0.01) or rituximab (13% vs 3%, p<0.01). Most MG cases were detected within a year after SLE diagnosis (Q25, Q75: 0, 12 years). With the median follow-up of 11 years (Q25, Q75: 6, 19 years), 34.8% (8 cases) of the SLE+MG cohort were diagnosed with malignancy, compared with 8.1% (82 cases) among the SLE controls (p<0.001). MG was associated with the relative hazard of death of HR 2.99 (95% CI 1.26 to 7.06, p<0.05) and a median survival time from SLE diagnosis to death of 5 years (Q25, Q75: 1, 14; range 0-41) for SLE+MG cases, as compared with 12 years (Q25, Q75: 6, 19; range 0-62) for the controls. The effect was non-independent on antimalarial medication use.

Our study emphasises heightened malignancy and mortality rates in SLE+MG cases. The association between immunosuppression, MG incidence and progression warrants further research.

Multiple myeloma (MM) is a malignant blood disease, but there have been significant improvements in the prognosis due to advancements in quantitative assessment and targeted therapy in recent years. The quantitative assessment of MM bone marrow infiltration and prognosis prediction is influenced by imaging and artificial intelligence (AI) quantitative parameters. At present, the primary imaging methods include computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). These methods are now crucial for diagnosing MM and evaluating myeloma cell infiltration, extramedullary disease, treatment effectiveness, and prognosis. Furthermore, the utilization of AI, specifically incorporating machine learning and radiomics, shows great potential in the field of diagnosing MM and distinguishing between MM and lytic metastases. This review discusses the advancements in imaging methods, including CT, MRI, and PET/CT, as well as AI for quantitatively assessing MM. We have summarized the key concepts, advantages, limitations, and diagnostic performance of each technology. Finally, we discussed the challenges related to clinical implementation and presented our views on advancing this field, with the aim of providing guidance for future research.

Extraosseous plasmacytomas (EPs) are rare neoplasms originating from plasma cells, often associated with multiple myeloma. EPs are classified into three subtypes: extramedullary myeloma, solitary extramedullary plasmacytoma (SEP), and multiple solitary plasmacytomas. They can manifest in various anatomical sites, including the lung, mediastinum, breast, liver, pancreas, stomach, mesentery, kidney, small and large bowel, testis, and soft tissue. Despite their rarity, EPs present a diagnostic challenge due to their non-specific imaging appearances, which can mimic other neoplastic and inflammatory conditions. This review aims to describe the radiographic features of EPs in the chest, abdomen, and pelvis based on a thorough analysis of the existing literature. While imaging plays a crucial role in the detection and characterization of EPs, histological confirmation is necessary to differentiate them from other neoplastic entities. The review underscores the importance of considering EPs in the differential diagnosis, particularly in patients with a history of multiple myeloma. Understanding the imaging characteristics of EPs is essential for accurate diagnosis and appropriate management. Early imaging is crucial in these patients to exclude the possibility of EP, as timely diagnosis can significantly impact patient outcomes.

Multiple myeloma often presents with vague and non-specific symptoms. Many patients are diagnosed in unplanned rather than elective (planned) diagnostic pathways. This study investigates the diagnosis of multiple myeloma in unplanned pathways and the association with patient characteristics, disease profile, and survival.

We conducted a nationwide register-based study, including all patients diagnosed with multiple myeloma in Denmark in 2014-2018. Patients were categorised as diagnosed in an unplanned pathway if registered with an acute admission within 30 days prior to the multiple myeloma diagnosis and no other previously registered pathway to this diagnosis. Unplanned pathways were compared to all other pathways combined.

We included 2,213 patients diagnosed with multiple myeloma, hereof 32% diagnosed in an unplanned pathway. Comorbidity, no prior cancer diagnosis, a history of few visits to the general practitioner (GP), multiple myeloma complications at diagnosis, high-risk cytogenetics, and advanced cancer stage were associated with a higher probability of being diagnosed in an unplanned pathway. For example, 24.4% (95% confidence interval (CI): 21.8-27.0) of patients with low comorbidity (Charlson Comorbidity Index (CCI) score 0) were diagnosed in an unplanned pathway as were 50.9% (95% CI: 45.6-56.1) of patients with high comorbidity (CCI score 3+). For patients with dialysis need at the time of diagnosis the probability was 66.0% (95% CI 54.2-77.8) and 30.9% (95% CI: 28.9-32.9) for patients with no dialysis need. Patients diagnosed in an unplanned pathway had inferior survival (hazard ratio 1.44 (95% CI: 1.26-1.64)). However, this association was not seen in analyses restricted to patients surviving for more than three years.

High comorbidity level, few usual GP visits, advanced disease status at diagnosis, and complications were associated with diagnosis in an unplanned pathway. Further, patients diagnosed in an unplanned pathway had inferior survival. Promoting earlier diagnosis and preventing unplanned pathways may help improve survival in multiple myeloma.

A second autologous stem-cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti-CD38 and immunotherapy, its role remains debated. We conducted a real-life study in 10 French centers (1996-2017) involving 267 RMM patients receiving ASCT2. The median age was 61 years, with 49% females. Most patients received melphalan 200 mg/m² before ASCT2, with low early mortality (1%). Very good partial response or better (VGPR+) rate post ASCT2 was 78%. Post ASCT2, 48% received consolidation therapy and 40% maintenance therapy. Median event-free survival (EFS) after ASCT2 was 2.6 years (95% confidence interval [CI]: 2.3-2.8), and 2-year EFS estimate was 63% (95% CI: 57-70). Median overall survival (OS) was 8.1 years (95% CI: 5.9-NA), and 2-year OS estimate was 92% (95% CI: 88-95). Multivariate analysis revealed that VGPR+ status and maintenance therapy post ASCT2 were associated with better EFS (hazard ratio [HR]: 0.6; 95% CI: 0.3-0.9, p = 0.012 and HR: 0.4; 95% CI: 0.3-0.6, p < 0.001, respectively) and OS (HR: 0.4; 95% CI: 0.2-0.9, p = 0.017 and HR: 0.2; 95% CI: 0.1-0.4, p < 0.001, respectively), while male sex correlated with poorer outcomes for EFS (HR: 2.5; 95% CI: 1.7-3.7, p < 0.001) and OS (HR: 2.7; 95% CI: 1.4-4.9, p = 0.002). Overall, ASCT2 appeared efficient with low toxicity in RMM. Maintenance therapy was associated with extended EFS and OS, particularly in patients with VGPR+ status post ASCT2. These findings underscore ASCT2's potential in RMM when coupled with maintenance therapy in selected patients.