Search Results (62)

Light-chain (AL) amyloidosis is a rare clonal plasma cell disorder that, if left untreated, carries a high risk of organ damage and mortality. Due to the rarity of the disease and the vulnerability of affected organ systems, treatment requires significant caution and nuance. As a plasma cell dyscrasia, AL amyloidosis treatment regimens are often adapted from those used for related disorders, particularly multiple myeloma. Despite substantial progress in research and drug development, optimal treatment strategies for relapsed/refractory (RR) AL amyloidosis remain unclear, and no FDA-approved therapies currently exist for this setting. B-cell maturation antigen (BCMA) has emerged as a promising immunotherapy target, with associated drug classes including antibody–drug conjugates, bispecific antibodies, and CAR-T cell therapies. These therapies have been extensively studied in relapsed/refractory multiple myeloma (RRMM) and are now being explored in the context of RR AL amyloidosis. This review summarizes the current literature on the efficacy and tolerability of BCMA-directed therapies in AL amyloidosis, with a particular emphasis on CAR-T cell therapy and offers comparisons to outcomes observed in RRMM. Full article

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell dyscrasia. According to revised diagnostic criteria, pPCL is defined by the presence of ≥5% circulating plasma cells (CPCs) in the peripheral blood of patients with newly diagnosed multiple myeloma (NDMM). pPCL is characterized by a distinct cytogenetic profile, including frequent t(11;14), MAF/MAB translocations, 1q gain, and del(17p). While t(11;14) is generally associated with a favorable prognosis, the coexistence of multiple high-risk cytogenetic abnormalities is linked to poorer outcomes. Tandem autologous hematopoietic stem cell transplantation and novel anti-myeloma agents have improved survival in some patients; however, overall prognosis remains poor, particularly in those ineligible for transplantation. Venetoclax and emerging immunotherapies, such as CAR-T cells and bispecific antibodies, show promise and merit clinical trials focused on pPCL-enriched cohorts. Additionally, recent findings associating even minimal CPCs with adverse outcomes in NDMM support broader inclusion criteria in future trials. A deeper understanding of pPCL’s molecular pathology is critical for the development of effective targeted therapies. This article reviews recent advances in the molecular understanding of and treatment strategies for pPCL. Full article

Background: The physical activity of different groups of individuals results in the rearrangement of microbiota composition toward a symbiotic microbiota profile. This applies to both healthy and diseased individuals. Multiple myeloma (MM), one of the more common hematological malignancies, predominantly affects older adults. Identifying an appropriate form of physical activity for this patient group remains a challenge. The aim of this study was to investigate the impact of a 6-week Nordic walking (NW) training program combined with a 10/14 time-restricted eating regimen on the gut microbiota composition of multiple myeloma patients. Methods: This study included healthy individuals as the control group (n = 16; mean age: 62.19 ± 5.4) and patients with multiple myeloma in remission (MM group; n = 16; mean age: 65.00 ± 5.13; mean disease duration: 57 months). The training intervention was applied to the patient group and consisted of three moderate-intensity sessions per week, individually tailored to the estimated physical capacity of each participant. The taxonomic composition was determined via 16S rRNA sequencing (V3–V9 regions). The microbiota composition was compared between the patient group and the control group. Results: The alpha and beta diversity metrics for species and genus levels differed significantly between the control and patient groups before the implementation of the NW program. In contrast, no differences were observed between the control and patient groups after the training cycle, indicating that the patients’ microbiota changed toward the pattern of the control group. This is confirmed by the lowest values of average dissimilarity between the MMB groups and the control at all taxonomic levels, as well as the highest one between the control group and the MMA patient group. The gut microbiota of the patients was predominantly represented by the phyla Firmicutes, Actinobacteria, Verrucomicrobia, Proteobacteria, and Bacteroidetes. Conclusions: The training, combined with time-restricted eating, stimulated an increase in the biodiversity and taxonomic rearrangement of the gut microbiota species. Full article

Background: Multiple myeloma, a malignancy of plasma cells, often involves the disruption of vitamin D metabolism. Vitamin D, acting through its receptor (VDR), affects transcription factors like FOXO and sirtuins, which regulate cellular processes. The impact of physical activity on these markers in multiple myeloma patients is unclear. Therefore, the objective of this study was to evaluate the effects of a 6-week training program on these parameters. Material and methods: The study was completed by 30 patients, including 16 in the Nordic walking training group (TG) and 14 in the control group (non-exercising, CG). All participants underwent a thorough medical interview before starting the project. Venous blood samples were collected from all participants four times—at baseline, after 3 weeks, after 6 weeks, and after 9 weeks (follow-up). The serum concentrations of sirtuin 1, sirtuin 3, Foxo3a, vitamin D receptor (VDR), 25(OH)D3, and 1,25(OH)2D were determined. Body composition, physical fitness, and physical activity level were assessed at baseline and after 6 weeks. Results: No statistically significant changes were observed in the serum levels of sirtuins, the FOXO3a protein, and 1,25(OH)2D. A statistically significant difference was observed in the levels of VDR for both time and group factors, but this was not confirmed in the post hoc test. Vitamin 25(OH)D3 level increased significantly in the study group with time. Conclusions: The applied 6-week Nordic walking training cycle positively affected the level of vitamin 25(OH)D3 but did not influence the rest of the biochemical parameters studied. The obtained results also indicate that the applied intervention is safe for patients and does not interfere with body composition. Full article

Background: Early reports suggest that hematological malignancy (HM) is a relevant risk factor for morbidity and mortality in COVID-19. We investigated the characteristics, outcomes, and risk factors for mortality in patients hospitalized with HM and COVID-19. Methods: We conducted a retrospective, nationwide study using data from hospitalized patients that were provided by the Spanish Ministry of Health including all patients admitted to a Spanish hospital from 2020 to 2022 with a COVID-19 diagnosis. A descriptive analysis and correlational analyses were conducted. Logistic regression was used to assess mortality in these patients and to calculate odds ratios (ORs). Results: We collected data on 1.2 million patients with COVID-19, including 34,962 patients with HMs. The incidence of hospitalization for patients with HMs was 5.8%, and the overall mortality rate was higher than for patients without HMs (19.8% versus 12.7%, p = 0.001). Mortality rates were higher for patients with lymphomas, multiple myelomas, and leukemias than for those with myeloproliferative disorders. Having HMs was a risk factor for mortality, with OR = 1.7 (95% CI 1.66–1.75, p = 0.001). By subtype, non-Hodgkin lymphomas were the highest risk factor for mortality (OR = 1.7), followed by leukemias (OR = 1.6), Hodgkin lymphomas (OR = 1.58), and plasma cell dyscrasias (OR = 1.24). Conclusions: This study identifies the different clinical profiles of patients with HMs who are at a high risk for mortality when hospitalized with COVID-19. As members of a vulnerable population, these patients deserve special prophylactic and therapeutic measures to minimize the effects of SARS-CoV-2 infection. Full article

Purpose: To evaluate the prediction of vertebral fractures in plasma cell dyscrasias using dual-layer CT (DLCT) with quantitative assessment of conventional CT image data (CI), calcium suppressed image data (CaSupp), and calculation of virtual calcium-only (VCa) image data. Material and Methods: Patients (n = 81) with the diagnosis of a plasma cell dyscrasia and whole-body DLCT at the time of diagnosis and follow-up were retrospectively enrolled. CI, CaSupp25, and CaSupp100 were quantitatively analyzed using regions of interest in the lumbar vertebral bodies and fractured vertebral bodies on baseline or follow-up imaging. VCa were calculated by subtraction (CaSupp100-CaSupp25), delineating bone only. Logistic regression analyses were performed to assess the possibility of imminent spine fractures. Results: In 24 patients, new vertebral fractures were observed in the follow-up imaging. The possibility of new vertebral fractures was significant for baseline assessment of CT numbers in CI, CaSupp25, and VCa (p = 0.01, respectively), with a higher risk for new fractures in the case of lower CT numbers in CI (Odds ratio = [0.969; 0.994]) and VCa (Odds ratio = [0.978; 0.995]) and in the case of higher CT numbers in CaSupp 25 (Odds ratio 1.015 [1.006; 1.026]). Direct model comparisons implied that CT numbers in CaSupp 25 and VCa might show better fracture prediction than those in CI (R² = 0.18 both vs. 0.15; AICc = 91.95, 91.79 vs. 93.62), suggesting cut-off values for CI at 103 HU (sensitivity: 54.2%; specificity: 82.5; AUC: 0.69), for VCa at 129 HU (sensitivity: 41.7%; specificity: 94.7; AUC: 0.72). Conclusions: Quantitative assessment with CaSupp and calculation of VCa is feasible to predict the vertebral fracture risk in MM patients. DLCT may prove useful in detecting imminent fractures. Full article

Background: The morbidity and mortality from AL amyloidosis has significantly improved with the development of novel treatments. Daratumumab is a highly effective treatment for AL amyloidosis, but end-stage kidney disease is a common complication of this condition. Kidney transplantation is the ideal form of renal replacement therapy but has historically been contraindicated in this group of patients. Methods: Given the improved survival and better treatments of both conditions, we argue that it is time to reconsider transplanting these patients. Results: We report our experience of transplanting four patients with AL amyloidosis who had achieved stable remission through treatment with daratumumab. Conclusions: We highlight the key challenges involved and discuss important clinical issues for patients receiving daratumumab, particularly the difficulties with interpreting the crossmatch in light of daratumumab and immunoglobulin therapy interference. We also discuss the complexities involved in balancing the risks of infection, relapse, rejection, and immunosuppression in such patients. Full article

Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part in the growth of immunotolerance conditions that make it easier for the development of neoplastic malignancies. Uncontrolled immune activation resulting in chronic inflammation is also known to be at the basis of the evolution toward neoplastic pathologies, as well as multiple myeloma. Another point is the impact that myeloma-specific therapies have on the course of concomitant autoimmune diseases. Indeed, cases have been observed of patients suffering from multiple myeloma treated with daratumumab and bortezomib who also benefited from their autoimmune condition or patients under treatment with immunomodulators in which there has been an arising or worsening of autoimmunity conditions. The role of bone marrow transplantation in the course of concomitant autoimmune diseases remains under analysis. Full article

Background: Multiple myeloma (MM) accounts for about 10–15% of all diagnosed hematologic malignancies and about 1–2% of all cancer cases. Approximately 80–90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Materials and methods: Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60 min workouts 3 times a week was conducted. Body mass and composition as well as the levels of vitamin D, calcium and phosphorus, beta2-microglobulin, and albumin were examined before and after the completion of the training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN), and Tartrate-resistant acid phosphatase 5b (TRACP 5b). Results: There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumins was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p = 0.001 and p = 0.022, respectively). The change in the concentration of this vitamin negatively correlated with the concentration of TRACP 5b (r = −0.413, p = 0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p = 0.026, time vs. group: p = 0.033) and TRACP 5b (time: p < 0.001, time vs. group p < 0.001) was indicated. Conclusions: The obtained results allow one to indicate the training with the poles as a safe and beneficial form of physical activity that should be recommended to patients suffering from MM. However, the results obtained in the present study are not sufficient to show the beneficial effect of IF applied without trainings. Full article

Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to multi-organ dysfunction. Treatment approaches have historically mirrored but lagged behind those of multiple myeloma (MM). Recent advancements in MM immunotherapy are gradually being evaluated and adopted in AL amyloidosis. This review explores the current state of immunotherapeutic strategies in AL amyloidosis, including monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapy. We discuss the unique challenges and prospects of these therapies in AL amyloidosis, including the exposure of frail AL amyloidosis patients to immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS), as well as their efficacy in promoting rapid and deep hematologic responses. Furthermore, we highlight the need for international initiatives and compassionate programs to provide access to these promising therapies and address critical unmet needs in AL amyloidosis management. Finally, we discuss future directions, including optimizing treatment sequencing and mitigating toxicities, to improve outcomes for AL amyloidosis patients. Full article

The clinical signs of multiple myeloma, a plasma cell (PC) dyscrasia, include bone loss, renal damage, and paraproteinemia. It can be defined as the uncontrolled growth of malignant PCs within the bone marrow. The distinctive bone marrow milieu that regulates the progression of myeloma disease involves interactions between plasma and stromal cells, and myeloid and lymphoid cells. These cells affect the immune system independently or because of a complicated web of interconnections, which promotes disease development and immune evasion. Due to the importance of these factors in the onset of disease, various therapeutic strategies have been created that either target or improve the immunological processes that influence disease progression. The immune system has a role in the mechanism of action of multiple myeloma treatments. The main contributions of immune cells to the bone marrow microenvironment, as well as how they interact and how immune regulation might lead to therapeutic effects, are covered in this study. Full article

The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138⁺⁾ PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8⁺T cells were incubated with sorted LAG-3^pos or LAG-3^neg PCs for 24 h. The expression of granzyme (Grz) in CD8⁺T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)/ SMM. Grz expression was significantly decreased in CD8⁺T cells incubated with CD138⁺LAG-3^pos PCs, compared to CD138⁺LAG-3^neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8⁺T cells. Full article

Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute to the development of drug resistance. The bone marrow microenvironment (BMME) is composed of a cellular component comprising stromal cells, endothelial cells, osteoclasts, osteoblasts, and immune cells, and a non-cellular component made of the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors, and chemokines. The bone marrow stromal cells (BMSCs) are involved in the adhesion of MM cells, promote the growth, proliferation, invasion, and drug resistance of MM cells, and are also crucial in angiogenesis and the formation of lytic bone lesions. Classical immunophenotyping in combination with advanced immune profiling using single-cell sequencing technologies has enabled immune cell-specific gene expression analysis in MM to further elucidate the roles of specific immune cell fractions from peripheral blood and bone marrow (BM) in myelomagenesis and progression, immune evasion and exhaustion mechanisms, and development of drug resistance and relapse. The review describes the role of BMME components in MM development and ongoing clinical trials using immunotherapeutic approaches. Full article

Multiple myeloma (MM) is an incurable hematologic malignancy originating from clonal plasma cell proliferation within the bone marrow, predominantly affecting older individuals. While anemia serves as a diagnostic criterion for MM, it often ameliorates upon achieving disease remission. Iron metabolism parameters have emerged as potential prognostic indicators in MM. Notably, physical exercise has been established to influence iron metabolism. This study aimed to assess alterations in serum iron, ferritin, and transferrin concentrations, as well as leukocyte gene expression, in MM patients undergoing a six-week cycle of Nordic walking training. Thirty patients divided into an exercise group (NW, n = 15, mean age 63.1 ± 8.4 years) and a control group (CG, n = 15, mean age: 63.5 ± 3.6 years) completed the study protocol. Blood samples were collected at baseline, after three and six weeks of training, and after nine weeks. Serum ferritin, transferrin, and iron concentrations were measured, along with the leukocyte expression of genes. Additionally, serum oxidative damage marker levels were determined. Following the Nordic walking training cycle, a declining trend in serum ferritin concentrations was observed. Intracellular mRNA levels of genes associated with iron metabolism were positively influenced by the training regimen, indicating the potential impact of this physical activity on gene expression and ferritin concentrations. Although positive trends were noted, extended training periods might be requisite for significant changes. To conclude, moderate-intensity exercise induces favorable shifts in the analyzed parameters among MM patients, potentially influencing disease progression. Consequently, Nordic walking training is a safe recommendation for MM patients, though sustained training beyond six weeks could be necessary for notable effects on iron metabolism factors. Full article

Acquired isolated factor VII (FVII) deficiency is a rare but important discovery in patients with plasma cell disorders with significant therapeutic and prognostic implications. The present analysis and review of cases reported in the literature is intended to highlight disease-related characteristics associated with this rare clotting defect, clinical manifestations and outcome, and potential underlying mechanisms, and to provide guidance on how to manage these patients in terms of prophylactic and therapeutic measures. The discovery of acquired FVII deficiency in a patient with multiple myeloma (MM) or monoclonal gammopathy of uncertain significance (MGUS) should prompt an evaluation for AL amyloidosis, particularly for amyloid hepatosplenic involvement, whenever not previously documented. Acquired FVII deficiency in patients with MM and AL amyloidosis is frequently associated with severe bleeding diathesis, also related to a number of concomitant predisposing factors, adversely affecting the outcome. The prompt institution of a rapidly acting therapy is crucial to prevent severe bleeding complications and positively impact outcome. Recombinant activated factor VII (rVIIa) may represent a useful supportive care measure, both in treating active bleeding and in the peri-procedural setting. However, further clinical experience is needed to optimize the therapeutic management of this rare disorder. Full article