Clonal Plasma Cells Research Articles

Прогностическое значение экспрессии галектина-1 опухолевыми плазматическими клетками и концентрации некоторых сывороточных цитокинов (IL-2, IL-6, TNF) у пациентов с моноклональной гаммапатией неопределенного значения и множественной миеломой

AIM. To study the prognostic value of the galectin-1 expression by bone marrow (BM) tumor plasma cells (PCs) and the concentration of serum cytokines (interleukins [IL-2, IL-6] and tumor necrosis factor [TNF]) in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (ММ). MATERIALS & METHODS. The trial enrolled 129 patients: 77 patients with newly diagnosed MM (median age 64 years) and 52 patients with MGUS (median age 62.5 years) followed-up at the Republican Scientific and Practical Center for Radiation Medicine and Human Ecology from 2018 to 2023. All patients underwent general clinical examination as well as BM aspirate cytology with myelogram and iliac BM core biopsy with immunohistochemical (IHC) analysis of BM biopsy. RESULTS. In the BM biopsy, the IHC analysis revealed a significant increase of galectin-1 expression (measured by expressing tumor PC count) in MM vs. MGUS patients (p < 0.001). Galectin-1 expression defined as expressing tumor PC count was significantly higher in patients with progressing MGUS compared to progression-free MM patients (p < 0.001). The median galectin-1 expression level was 8.5 % (Q25 0.2 %; Q75 15.7 %) in progression-free MGUS patients and 37.4 % (Q25 24.7 %; Q75 64.0 %) in progressing MGUS patients. Among MM patients, no significant differences were identified either in those with and without tumor progression. The IHC analysis of BM core biopsies in MM patients showed that high galectin-1 expression level is associated with pronounced vasculature but not with fibrotic changes, it also identified an increase in serum concentrations of IL-2 and TNF as well as a direct correlation with β2-microglobulin level. With MGUS progression into ММ, there was a direct correlation between galectin-1 expression level and serum M-protein. An increase of IL-2 concentration was registered only when MGUS progressed into ММ. CONCLUSION. The results of this study indicate the evidence of a high level of galectin-1 expression by tumor PCs in MM. In MGUS, an increase of galectin-1 expression by clonal BM PCs was associated with the disease progression. Galectin-1 expression by clonal BM PCs can well be clinically used as a marker for MGUS progression into MM.

Global disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study

Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare. This study utilized the openFDA human drug adverse events (AEs) to analyze global data pertaining to MM patients and patterns of treatment-related AEs. We identified ten most frequently used drugs and drug regimens in six distinct regions, including North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America & the Caribbean (LA). AE patterns were evaluated using the reporting odds ratio combined with a 95% confidence interval. AE reports were more prevalent in men than in women across all regions. Cardiotoxicities were more likely observed in AS and EU, while secondary neoplasms were more frequently reported in the EU. Nephropathies were prominent in OC, AF (in males), and AS (in females), while vascular toxicity, including embolism and thrombosis, was more common in NA (in males). A notable improvement in survival, particularly in AS, EU, and NA, with a significant decline in death rates was observed. Hospitalization rates displayed less variation in AS and EU but exhibited more pronounced fluctuations in AF, LA, and OC. In conclusion, this comprehensive analysis offers valuable insights into the demographic, geographic, and AE patterns of MM patients across the globe.

The significance of free light-chain ratio in light-chain monoclonal gammopathy of undetermined significance: a flow cytometry sub-study of the iStopMM screening study

Light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. LC-MGUS is characterized by free light-chain (FLC) levels outside defined reference intervals, indirectly indicating underlying plasma cell (PC) monoclonality. Next-generation flow cytometry (NGF) was used to evaluate clonal PC presence in bone marrow (BM) samples from individuals with LC-MGUS in the iStopMM study, aiming to assess the predictive value of the FLC ratio for clonal PC presence and its prognostic implications. BM samples from 61 individuals with LC monoclonal gammopathy were analyzed. Clonal plasma cells were detected in 53.6% of LC-MGUS samples (n = 28) and in all samples from individuals with more advanced conditions (n = 33). The FLC ratio was predictive of clonal PC presence for kappa-involved FLC ratios (p < 0.05; n = 42), with an optimal cutoff of 3.15 (96.7% sensitivity, 91.7% specificity). Of 195 individuals with kappa-involved LC-MGUS in follow-up within the iStopMM study, none with FLC ratios >1.65 to 3.15 progressed to MM (n = 124), whereas 4/71 (5.6%) with FLC ratios >3.15 progressed over median follow-up of 55 months. These findings support using a kappa-involved FLC ratio cutoff of >3.15 to more accurately identify individuals at increased risk of developing symptomatic PC disorders.

Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells

Immune surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a previously unknown function for intracellular C3d, we found that C3d engaged T cell responses against malignant PC in the bone marrow of mice that had developed multiple myeloma spontaneously. Our results show that C3d internalized by cells augments immune surveillance by several mechanisms. In one, C3d induces a master transcription regulator, E2f1, to increase the expression of long noncoding (lnc) RNAs, to generate peptides for MHC-I presentation, and increase MHC-I expression. In another, C3d increases expression of RNAs encoding ribosomal proteins linked to processing of defective ribosomal products that arise from noncanonical translation and known to promote immunosurveillance. Cancer cells are uniquely susceptible to increased expression and presentation of mutant peptides given the extent of protein misfolding and accumulation of somatic mutations. Accordingly, although C3d can be internalized by any cell, C3d preferentially targets malignant clones by evoking specific T cell-mediated immunity and sparing most nontransformed polyclonal B cells and PC with lower mutation loads. Malignant PC deletion was blocked by cyclosporin or by CD8 depletion confirming that endogenous T cells mediated malignant clone clearance. Besides the potential for therapeutic application our results highlight how intracellular C3d modifies cellular metabolism to augment immune surveillance.

Neurological manifestations of MGUS.

Monoclonal gammopathy of undetermined significance (MGUS) is a highly prevalent disorder characterized by a small bone marrow plasma cell or lymphoplasmacytic clone (less than 10%) that produces a small amount of monoclonal paraprotein without associated organ damage. Most patients with MGUS display benign behavior indefinitely, but some progress to an overt malignancy, and others develop organ damage despite no increase in monoclonal protein, resulting in the so-called MG of clinical significance (MGCS). This concept includes different disorders depending on the organ involved, and among them, MG of neurological significance (MGNS) constitutes a real challenge from both a diagnostic and therapeutic point of view. Diagnosis is particularly difficult due to MGNS's heterogeneous clinical presentation and common lack of a diagnostic biopsy. On the other hand, the complexity of treatment lies in the lack of standardized regimens and the common irreversibility of neurological damage. Focusing on the neurological manifestations of MGUS affecting the peripheral nervous system, we describe 3 illustrative cases from daily practice and discuss different aspects of diagnosis to treatment, emphasizing the need for multidisciplinary management based on the close collaboration of neurologists and hematologists.

Extending Amyloidosis Diagnosis: A Rare Case of Peritoneal AL Amyloidosis Revealed by 18F-FDG PET/CT and 99mTc-PYP SPECT/CT.

We present a case with systemic amyloidosis secondary to immunoglobulin light-chain amyloidosis (AL amyloidosis), which 18F-FDG PET/CT and 99mTc-PYP scintigraphy revealed amyloid deposition in the peritoneum, omentum, and mesentery. AL amyloidosis is characterized by the proliferation of clonal plasma cells and increased production and extracellular accumulation of immunoglobulin light chains, leading to organ malfunction. Even though AL amyloidosis can affect the gastrointestinal system, peritoneal involvement is rarely observed. PET/CT and SPECT/CT images showed moderate to slightly increased tracer uptake in affected organs.

Renal manifestations of MGUS.

Kidney disease is a common complication of monoclonal immunoglobulin (MIg)-secreting B-cell disorders and predominantly occurs in patients who do not meet the criteria for an overt hematological disease. To distinguish this situation from monoclonal gammopathy of undetermined significance, which lacks organ damage, the term monoclonal gammopathy of renal significance (MGRS) was introduced to depict the association of a small, otherwise indolent B-cell clone, with renal disease induced by the secreted MIg. The spectrum of renal disorders in MGRS is wide, encompassing both tubular and glomerular disorders, classified according to the composition of deposits and their ultrastructural pattern of organization. Renal lesions, independent of the tumor burden, are mostly governed by the molecular characteristics of the MIg variable domain and involve either direct (deposition or precipitation) or indirect (autoantibody activity, complement activation) mechanisms. The diagnosis, often suggested by careful analysis of renal and extrarenal symptoms, almost always requires histological confirmation by a kidney biopsy with light, immunofluorescence, and electron microscopy studies. Most patients do not have a known monoclonal gammopathy at presentation. Hematologic investigations should include serum and urine protein electrophoresis and immunofixation, serum-free light chain measurements, and bone marrow studies with flow cytometry and cytogenetics to determine the nature of the pathogenic clone (most commonly plasmocytic). Early diagnosis before the development of severe chronic kidney disease and rapid achievement of deep hematological response through clone-targeted chemotherapy (currently based on proteasome inhibitor and monoclonal anti-CD38 antibody-based combinations for plasma cell clones) are the main factors influencing long-term renal and patient outcomes.

Comparison of 6 cycles of isatuximab with lenalidomide, bortezomib and dexamethasone (I-VRd) versus 3 cycles of I-VRd followed by one cycle of high-dose melphalan in newly diagnosed low-risk multiple myeloma. Protocol for a multicenter, prospective, randomized, phase II clinical trial (ELIAS-Trial)

Newly diagnosed multiple myeloma patients who are eligible for transplant usually receive several induction cycles of therapy, followed by one or two cycles of high-dose melphalan and autologous stem cell transfusion. In myeloma patients, high-dose melphalan improves overall survival and progression-free survival. However, melphalan exposure increases the risk of secondary malignancies and may lead to the transformation of residual myeloma cells into more aggressive clones, which may accelerate relapse. It remains to be determined whether low-risk patients also derive additional benefit from high-dose melphalan therapy compared with less toxic regimens. Here we publish the study protocol of a multicenter, interventional, controlled, randomized, prospective and open-label phase II trial to investigate whether patients with a low-risk profile (R-ISS stage I, characterized by a low tumor burden and the absence of negative cytogenetic findings or elevated LDH levels) and a standard-risk gene expression profile (using the SKY92 GEP assay) can be sufficiently treated with intensified consolidation regimens without prior high-dose melphalan chemotherapy. The primary objective is to assess whether three cycles of isatuximab, bortezomib, lenalidomide and dexamethasone (I-VRd) followed by stem cell apheresis and three additional cycles of I-VRd will result in a non-inferior rate of complete remission (CR) combined with MRD-negativity at week 40 after the start of induction therapy compared to three cycles of I-VRd followed by standard of care treatment (such as stem cell apheresis, high-dose melphalan, and autologous stem cell transplantation). We hypothesize that this approach could reduce toxicity, cost of treatment and the likelihood of the development of a more malignant plasma cell clone, while improving overall survival (OS) and progression-free survival (PFS) in newly diagnosed low risk myeloma patients.EU Trial Number2022-500453-16-00, https://clinicaltrials.gov/study/NCT05665140, identifier NCT05665140. Registration Date: 21.07.2022.

MGCS: where do we stand today?

Monoclonal gammopathies of clinical significance (MGCS) are a heterogeneous group of disorders characterized by the presence of an indolent B-cell or plasma-cell clone producing a toxic monoclonal immunoglobulin resulting in end-organ dysfunction. MGCS is a clinicopathologic diagnosis that requires the demonstration of a monoclonal immunoglobulin in the correct clinical setting. The most common MGCS syndromes are renal, neurologic, and cutaneous, although hematologic and multi-organ MGCS syndromes are also increasingly recognized. Therapy most commonly targets the underlying clonal population; immunoglobulin-targeting therapies as well as complement and cytokine antagonists have emerged for selected MGCS syndromes and may be temporizing in a subset of patients. Other chapters review renal and neurologic MGCS; this chapter focuses on hematologic and multi-organ MGCS syndromes.

Guidelines for the diagnosis and management of multiple myeloma in China (2024 revision)

Multiple myeloma (MM), an incurable clonal plasma cell dysplasia, is the second most common hematological malignancy in many countries, mainly developing in the elderly population. With the emergence of novel agents and laboratory methods, the diagnosis and treatment of MM have been significantly improved. In this version of the "Guidelines for the diagnosis and management of multiple myeloma in China (2024 revision)", several examination items have been updated in the diagnostic section; the definition of ultra high-risk MM has been proposed in the risk stratification section; for patients with equal or more than second-line relapse, chimeric antigen receptor T cell therapy and a bispecific T-cell engager have been added; and the treatment recommendations have been listed at different levels based on the best available evidence.

Update on kidney injury caused by multiple myeloma.

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.

Autologous stem cell transplantation for multiple myeloma patients whose myeloma-defining event was SLiM.

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.

Novel CCL3-HMGB1 signaling axis regulating osteocyte RANKL expression in multiple myeloma.

Multiple myeloma (MM) is a clonal plasma cell proliferative malignancy characterized by a debilitating bone disease. Osteolytic destruction, a hallmark of MM, is driven by increased osteoclast number and exacerbated bone resorption, primarily fueled by the excessive production of RANKL, the master regulator of osteoclast formation, within the tumor niche. We previously reported that osteocytes, the most abundant cells in the bone niche, promote tumor progression and support MM bone disease by overproducing RANKL. However, the molecular mechanisms underlying RANKL dysregulation in osteocytes in the context of MM bone disease are not entirely understood. Here, we present evidence that MM-derived CCL3 induces upregulation of RANKL expression in both human and murine osteocytes. Through a combination of in vitro, ex vivo, and in vivo models and clinical data, we demonstrate that genetic or pharmacologic inhibition of CCL3 prevents RANKL upregulation in osteocytes and attenuates the bone loss induced by MM cells. Mechanistic studies revealed that MM-derived CCL3 triggers the secretion of HMGB1 by osteocytes, a process required for osteocytic RANKL upregulation by MM cells. These findings identify a previously unknown CCL3-HMGB1 signaling axis in the MM tumor niche that drives bone resorption by promoting RANKL overproduction in osteocytes.

Clinical characteristics of monoclonal immunoglobulin-associated renal disease: a retrospective cohort study.

Clinical epidemiological data on monoclonal gammopathy of renal significance (MGRS) are lacking. In this retrospective observational study, MGRS was compared with B-cell or plasma cell malignancies (BCM/PCM) with renal involvement to clarify differences in their clinical features. Among the 1408 renal biopsies performed at our hospital, 25 MGRS and 18 BCM/PCM patients were identified. We investigated baseline characteristics and hematologic parameters of MGRS in reference to BCM/PCM using multivariable analysis. Cox proportional hazards analysis was performed for end-stage kidney disease (ESKD) and all-cause mortality. Comparing the MGRS with the BCM/PCM, meandifferences in creatinine level, estimated glomerular filtration rate, and clonal bone marrow plasma cell percentage were -2.76mg/dL, 27.72mL/min/1.73m2, and -18.86%, respectively (all P < 0.001). MGRS group had a predominance of glomerular lesions such as immunoglobulin-associated amyloidosis, cryoglobulinemic GN, and MIDD, and a lower risk of acute kidney injury/acute renal disease compared to BCM/PCM. During a median observation period of 23.7months, clone-directed therapy was performed in 32.0% of patients in the MGRS group, compared to 83.3% of patients in the BCM/PCM group. Compared with BCM/PCM, MGRS had a hazard ratio of 0.66 (95% confidence interval (CI) 0.23-1.92, P = 0.45) for ESKD and 0.33 (95% CI 0.11-1.03, P = 0.06) for death in multivariate logistic regression analysis. The clinical characteristics of MGRS and BCM/PCM with monoclonal immunoglobulin-associated renal disease are disparate. Understanding these differences is crucial for developing tailored clinical approaches and therapeutic strategies to improve patient outcome.

Differential Detection of Clonal Bone Marrow Plasma Cells in IgA Vs. IgG Monoclonal Gammopathy of Undetermined Significance and Its Association with Disease Progression

Differential Detection of Clonal Bone Marrow Plasma Cells in IgA Vs. IgG Monoclonal Gammopathy of Undetermined Significance and Its Association with Disease Progression

The Association between Rheumatological Diseases and Monoclonal Gammopathy of Undetermined Significance

Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic clonal plasma cell disorder with the risk of progression to multiple myeloma (MM). Studies have shown that patients with rheumatological diseases (RD) are associated with an increased risk of progression of MGUS to MM. RD also exhibit higher prevalence of MGUS compared to the general population. Immunological dysregulation and chronic antigen stimulation from autoimmune activity are proposed mechanisms. We assessed the association between RD and MGUS development in the nationwide Veteran Health Administration database, thereby contributing to a deeper understanding of this relationship and its clinical implications. Methods: Patients with RD diagnosis (≥2 outpatient ICD 9/10 codes or ≥1 inpatient code) from 1999-2021 were included. Exclusions applied to patients with MGUS diagnosis (identified by a published natural language processing model), MM (ICD-9-CM/ICD-10-CM: C90/203.0/C90), non-Hodgkin lymphoma (202.85/C85), Waldenstrom's macroglobulinemia and other B-cell lymphomas (273.3/C88), or an amyloidosis (277/E85) prior to or &amp;lt;6 month of RD diagnosis. The first RD diagnosis was defined as the index date, with index age as the age at RD diagnosis. Follow-up time was from the index date to MGUS diagnosis/death/censoring (12/31/2021) which ever came first. Patients with RD were 1:2 matched to individuals without RD on their follow-up time (and determined their index date/age), followed by matching on their index age (±1 year). The same exclusion criteria were applied to individuals without RD. To account for potential bias due to more frequent care because of comorbidities, the cohort was further stratified by Charlson Comorbidity Index (CCI) at index date (high vs low based on median CCI). CCI was computed using ICD codes to identify diseases diagnosed &amp;lt;5 years before and 1 year after the index date. RD was categorized into antibody (Ab)-mediated and non-antibody (non-Ab) mediated RD. Stratified by CCI (high and low), multivariable logistic regression was conducted to analyze the association between RD (Ab and non-Ab mediated) and MGUS using multivariable-adjusted odds ratio (aOR). The covariates included sex, race (non-Hispanic White, non-Hispanic Black, Hispanic, Other), index age, body mass index (underweight, normal, overweight, obese), marital status (divorced/separated/widow, married, single), rurality (rural, urban), and CCI. Results: We analyzed data of 118,365 veterans; 39,455 had RD (80% non-ab-mediated, 20% Ab-mediated). Mean age was 54 years in both RD and non-RD groups by matching. Most patients were male (88.5% RD, 85.1% non-RD). Racial composition was similar: 56.5% non-Hispanic White, 26.0% non-Hispanic Black, and 6.9% Hispanic in the RD group, and 56.0%, 21.6%, 6.9% respectively in non-RD group. Median CCI was higher in the RD group (1 vs. 0). Most patients were obese (51.7% RD, 42.5% non-RD) or overweight (31.0% RD, 37.2% non-RD). In patients with high CCI (n=64,343), Ab-mediated RD (n=7,326) was associated with increased MGUS risk (aOR 2.1, 95% Confidence Interval [CI] 1.8-2.4, p&amp;lt;.0001) as was non-Ab mediated RD (n=20,830) (aOR 2.0, 95% CI 1.9-2.2, p&amp;lt;.0001) compared to patients without RD (n=36,187). In the low CCI group (n=54,022), non-Ab mediated RD (n=10,738) was associated with an increased risk of MGUS (aOR 4.4, 95% CI 3.3-5.7, p&amp;lt;0.0001) compared to patients without RD (n=42,723). There was not sufficient evidence to show that Ab-mediated RD (n=561) was associated with higher MGUS risk (aOR 2.6, 95% CI 0.49-13.7, p=0.26). Conclusions: In a retrospective cohort of US veterans, RD was associated with a higher incidence of MGUS. Both Ab-mediated and non-Ab mediated RD were associated with a higher risk of MGUS diagnosis in patients with higher burden of comorbidities. In patients with fewer comorbidities, only non-Ab-mediated RD was associated with MGUS, likely due to a small number of patients with Ab-mediated RD. Bias in MGUS assessment should be considered, as patients with RD may undergo more testing, leading to increased detection of MGUS. Future prospective studies are needed to evaluate this association and if presence of the RD increases risk of progression to MM.

Development of Novel Peripheral Blood Count-Based Prognostic Index for Multiple Myeloma

In multiple myeloma (MM), clonal plasma cells evade immune surveillance and proliferate within an inflammatory bone marrow microenvironment. During pathogenesis, monocyte-derived tumor-associated macrophages help myeloma cells to avoid apoptosis; effector T cell lymphocytes undergo senescence to enable preferential upregulation of their immunosuppressive regulatory T cell counterparts; and myeloma cells interact with hematopoietic stem cells to inhibit downstream megakaryocyte differentiation into platelets.1 Our prior research has suggested a prognostic role for the absolute monocyte count (AMC), absolute lymphocyte count (ALC), and platelet count as biomarkers. We have shown that abnormal AMC and decreased ALC and platelet count are associated with decreased overall survival (OS) among patients with MM at diagnosis and follow-up. Based on the easy accessibility of these peripheral blood markers and need for dynamic prognostication among patients with MM undergoing novel therapies, we created a categorical peripheral blood-based prognostic index for MM incorporating AMC, ALC and platelet count. We retrospectively evaluated this index in 10790 patients diagnosed with MM between 2000 and 2019 at Veterans Administration hospitals using cell counts obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into 3 levels based on a logarithmic risk score, where those with the lowest counts across all cell lines (AMC, ALC, and platelet count) were in level III and those with counts approaching normalcy were in level I. At diagnosis, 8% of patients were in level III and had the highest risk of death (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.85-2.24; P &amp;lt; .01) compared to those in levels I (HR 1.15; 95% CI, 1.08-1.23; P &amp;lt; .01) and II (HR 1.37; 95% CI, 1.28-1.46; P &amp;lt; .01). Moreover, the risk of inferior OS associated with level III status persisted during treatment and follow-up and existed independently of other known risk stratification tools (including Charlson comorbidity index, lactate dehydrogenase, International Staging System classification). With further validation, our findings support the use of our novel prognostic index, which potentially reflects the underlying tumor microenvironment, as an available tool for risk stratification during the MM disease course.

Early experience with daratumumab-containing regimens in patients with light-chain cardiac amyloidosis

BackgroundImmunoglobulin light-chain (AL) amyloidosis is a lethal condition resulting from misfolded immunoglobulin ALs produced by clonal CD38-positive plasma cells. Treatment with daratumumab, an anti-human CD38 monoclonal antibody, led to higher frequencies of complete hematologic response and better clinical outcomes compared with conventional treatment. This study sought to evaluate the survival benefit of daratumumab-containing regimens in patients with AL cardiac amyloidosis. Methods and resultsWe examined 65 consecutive patients with AL cardiac amyloidosis (mean age: 67.2 ± 10.4 years, male: 69 %) who underwent chemotherapy. We divided patients into a daratumumab group, which used daratumumab-containing regimens before second-line treatment (n = 32), and a conventional treatment group (n = 33). Compared with the conventional treatment group, the daratumumab group tended to be older, but there were no significant differences between groups in biomarkers and echocardiographic parameters. A total of 26 patients (40 %) died (median follow-up duration: 395 days). Kaplan–Meier survival analysis showed that the daratumumab group had significantly lower mortality compared with the conventional treatment group (p = 0.04; log-rank test). Cox hazard analysis revealed that use of daratumumab-containing regimens was associated with lower mortality after adjustment for the revised Mayo staging of AL amyloidosis (hazard ratio: 0.32; 95 % confidence interval: 0.12 to 0.85; p = 0.02). ConclusionDaratumumab-containing regimens may be associated with improved survival in patients with AL cardiac amyloidosis.

The Prevalence of Blastocystis Hominis and Gastrointestinal System Parasites in Patients With Newly Diagnosed Multiple Myeloma Diagnosis

Introduction: Multiple myeloma (MM) is a hematological malignancy characterized by the presence of abnormal clonal plasma cells in the bone marrow. Immunodeficiency seen in patients with multiple myeloma (MM) is a serious problem. Blastocystis sp. is found in the gastrointestinal tract and can infect humans. Background/ Aims: In our study, we compared the prevalence of B.hominis and other parasites with the control group and patients who had recently been diagnosed with multiple myeloma. Material-Methods: Ninety-five multiple myeloma patients from our center and 95 volunteers as a control group were included in our study. The patients did not have any symptoms when stool samples were taken. For B.hominis, three consecutive stool samples were examined by saline-lugol trichrome staining and formalin-ethyl acetate concentration. Data were recorded and analyzed using SPSS 25.0. Results: Patients with newly diagnosed multiple myeloma and any of the patients in the control group did not have any parasites other than B.hominis. A significant difference was found between the newly diagnosed MM patients and the control group in terms of the number of B.hominis occurrences in the stool (p &amp;lt;0.001). Conclusions: According to this result, parasite load in stool increased in patients with MM. This result may reflect the suppression of the immune system of patients with MM. Accordingly, B.hominis should be considered as a causative agent in the presence of gastrointestinal symptoms that may occur during treatment in patients with MM.

Chimeric Antigen Receptor T Cells for the Treatment of Multiple Myeloma.

Multiple myeloma (MM), characterized by abnormal proliferation of clonal plasma cells, is an incurable hematological malignancy. Various immunotherapy strategies have emerged as an efficacious approach for the treatment of MM, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cells. Anti-B-cell maturation antigen (BCMA) CAR-T cells have revolutionized the treatment of MM patients with relapsed/refractory disease and their clinical use was approved for the treatment of these patients. Despite this progress, the efficacy of CAR-T cells in MM is limited by the responsiveness of only a part of the treated patients, the relapse of other patients, the cost of the treatment and the diminished response in patients with prior exposure to anti-BCMA targeting agents. Ongoing clinical trials are evaluating the use of CAR-T cells at an earlier stage of MM disease and the use of CAR-T cells targeting other membrane antigens expressed on malignant plasma cells.