Search Results (55)

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

Rare plasma cell disorders—including IgD, IgE, and IgM multiple myeloma, non-secretory myeloma (NSMM), plasma cell leukemia (PCL), and heavy chain disease (HCD)—are biologically heterogeneous and often present with atypical features and aggressive behavior. This review synthesizes current evidence on their epidemiology, pathophysiology, diagnosis, and treatment. Advances in proteasome inhibitors, immunomodulatory agents, and autologous transplantation have improved outcomes in select subtypes. However, challenges persist in distinguishing IgM myeloma from Waldenström macroglobulinemia, monitoring non-secretory disease, and treating highly aggressive forms such as IgE myeloma and PCL. Standardized diagnostic criteria and prospective trials are essential to guide future management. Full article

Background/Objectives: Bence Jones proteins (BJPs) are monoclonal immunoglobulin free light chains (FLCs) that appear in the urine of patients with plasma cell disorders, including multiple myeloma (MM), Waldenström’s macroglobulinemia (WM), or light chain amyloidosis (AL). Their presence can provide valuable information about disease progression and treatment efficacy. These proteins are typically detected through a 24-h urine collection, as recommended by clinical guidelines. However, this method can be inconvenient for both patients and laboratory personnel due to its time-consuming nature and the potential for collection errors. We propose an algorithm based on serum FLC (sFLC) to rule out the presence of BJPs and diminish the need for urine testing. Methods: A retrospective data analysis of 268 serum and urine samples from 44 patients with MM was performed, and cutoffs were established to predict BJP absence: total urine protein (0.115 g/L), sFLC κ/λ ratio (>0.82 λ monoclonality and <1.99 κ monoclonality), and difference of involved–uninvolved FLC (dFLC; <11.93 mg/L). A subsequent algorithm validation was performed in 716 samples from patients who underwent the same testing in routine 2023 other laboratory activity. Results: The validation of these cutoffs to rule out the presence of BJP showed that, if the protocol based on the sFLC κ/λ ratio and dFLC had been applied, 42% of the urine studies would have been avoided, achieving a sensitivity of 93.9% and a false negative rate of 6.11%. Conclusions: We propose a laboratory work protocol that would allow for the avoidance of almost half of the 24-h urine studies based on sFLC measurement, a faster and more objective alternative to urine analysis for screening out the presence of BJP, with a good sensitivity and a low false negative rate. Full article

In the evaluation of a patient’s primary hematologic malignancy, positron emission tomography/computed tomography (PET/CT) imaging may incidentally detect a concerning abnormality suggestive of a second concurrent cancer. Despite accounting for nearly 10% of all cancers diagnosed in Canada, there has yet to be a systematic review focused on the prevalence and significance of these incidental PET/CT findings in the context of primary hematologic malignancies. As such, a systematic search strategy was employed on MEDLINE and Embase to document the prevalence and clinical significance of incidental PET/CT findings suggestive of a second concurrent cancer detected in patients evaluated for their primary hematologic malignancy. Thirteen studies published between 2008 and 2022 were reviewed, including conference abstracts (n = 8) and journal articles (n = 5). Clinically significant incidental cancers were detected with a median of 2.4% (range: 1.1–10.3%) in patients with myeloma/plasma cell disorders, compared to a median of 1.5% (range: 0.3–2.8%) in patients with lymphoproliferative diseases. The most common anatomic regions of clinically significant incidental malignancies were identified in the gastrointestinal tract (44.4%), followed by the thyroid gland (22.2%) and lungs (7.9%). In most cases, early detection of incidental cancers led to successful early interventions. PET/CT scans occasionally identify second primary malignancies that require additional attention. These findings may affect the treatment of a patient’s primary hematologic malignancy, and as such, timely coordinated management is important for improved outcomes. This review may inform physicians and administrators of the risk of incidental second malignancies and may highlight a need for enhanced cancer treatment pathways. Full article

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the accumulation of abnormal plasma cells in the bone marrow. Mesenchymal stem cells (MSCs) and reticulated platelets (RPs) have been implicated in the pathogenesis of MM. This narrative review aims to explore the role of MSCs and RPs in the pathophysiology of MM, particularly their clinical use as possible variables of prognostic value in this hematologic neoplasia. The interaction between MSCs and MM cells within the bone marrow microenvironment supports MM cell survival, proliferation, and drug resistance. MSCs contribute to the development and maintenance of MM through the secretion of various factors, including cytokines, chemokines, and growth factors. Moreover, RPs, young and highly reactive platelets, have been implicated in promoting angiogenesis, tumor growth, and metastasis in MM. Several studies show that cells such as MSCs and platelets participate actively in the biology of the disease. Still, in clinical practice, they are not considered part of evaluating affected patients. In this review, we explore the possibility of including the evaluation of MSCs and PRs in the clinical practice for patients with MM as part of the strategies to improve the outcomes of this disease. 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

The term monoclonal gammopathy of clinical significance (MGCS) refers to a group of symptomatic monoclonal gammopathies that do not meet the diagnostic criteria for malignant plasma cell disorders, such as multiple myeloma or Waldenström macroglobulinemia. These symptoms are attributable to the paraneoplastic effects of monoclonal immunoglobulins that occur through diverse mechanisms. The presence of symptoms distinguishes MGCS from monoclonal gammopathy of undetermined significance, which lacks significant symptomatic presentation. The presentations of MGCS are manifold, adding to the diagnostic challenge. Clinical suspicion is key for accurate and timely diagnosis. Radiologic imaging can provide pivotal information to guide the diagnosis. In this review, we discuss MGCS from a radiology perspective and highlight pertinent imaging features associated with the disorders. 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

Background: Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35–71% of MM patients. Interleukin 1 beta (IL-1β) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1β in the assessment of the risk of nutritional disorders and prognosis in patients with MM. Methods: In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1β ELISA kit was used to determine IL-1β concentration in plasma samples. Results: Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1β in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1β plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). Conclusions: Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1β may be useful in the assessment of the risk of cachexia and prognosis in patients with MM. Full article

Light chain measurements form an essential component of the testing strategy for the detection and monitoring of patients with suspected and/or proven plasma cell disorders. Urine-based electrophoretic assays remain at the centre of the international guidelines for response assessment but the supplementary role of serum-free light chain (FLC) assays in response assessment and the detection of disease progression due to their increased sensitivity has been increasingly recognised since their introduction in 2001. Serum FLC assays have also been shown to be prognostic across the spectrum of plasma cell disorders and are now incorporated into risk stratification scores for patients with monoclonal gammopathy of undetermined significance (MGUS), smouldering multiple myeloma, and light chain amyloidosis (AL amyloidosis), as well as being incorporated into the criteria for defining symptomatic multiple myeloma. There are now multiple different commercially available serum FLC assays available with differing performance characteristics, which are discussed in this review, along with the implications of these for patient monitoring. Finally, newer methodologies for the identification and characterisation of monoclonal FLC, including modifications to electrophoretic techniques, mass spectrometry-based assays and Amylite, are also described along with the relevant published data available regarding the performance of each assay. Full article

Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid β-glucocerebrosidase (Gcase). Three clinical forms of Gaucher’s disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol–acetonitrile–water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = −0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1–157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring. Full article

Multiple myeloma (MM) is a hematological malignancy caused by malignant proliferation of plasma cells in bone marrow. Over the last decade, the survival outcome of patients with multiple myeloma (MM) has been substantially improved with the emergence of novel therapeutic agents. However, MM remains an incurable neoplastic plasma cell disorder. In addition, almost all MM patients inevitably relapse due to drug resistance. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. In this study, NK92 cells were engineered to express the third generation of BCMA CAR. In vitro, BCMA CAR-engineered NK92 cells displayed higher cytotoxicity and produced more cytokines such as IFN-γ and granzyme B than NK92 cells when they were co-cultured with MM cell lines. Furthermore, BCMA CAR-engineered NK92 cells released significantly higher amounts of cytokines and showed higher cytotoxicity when they were exposed to primary cells isolated from MM patients. The cytotoxicity of BCMA CAR NK92 cells was enhanced after MM cells were treated with bortezomib. Additionally, BCMA CAR NK92 cells exhibited potent antitumor activities in subcutaneous tumor models of MM. These results demonstrate that regional administration of BCMA CAR NK92 cells is a potentially promising strategy for treating MM. Full article

Multiple myeloma is a hematologic neoplasm caused by abnormal proliferation of plasma cells. Sequencing studies suggest that plasma cell disorders are caused by both cytogenetic abnormalities and oncogene mutations. Therefore, it is necessary to detect molecular abnormalities to improve the diagnosis and management of MM. The main purpose of this study is to determine whether NGS, in addition to cytogenetics, can influence risk stratification and management. Additionally, we aim to establish whether mutational analysis of the CD138 cell population is a suitable option for the characterization of MM compared to the bulk population. Following the separation of the plasma cells harvested from 35 patients newly diagnosed with MM, we performed a FISH analysis to detect the most common chromosomal abnormalities. Consecutively, we used NGS to evaluate NRAS, KRAS, BRAF, and TP53 mutations in plasma cell populations and in bone marrow samples. NGS data showed that sequencing CD138 cells provides a more sensitive approach. We identified several variants in BRAF, KRAS, and TP53 that were not previously associated with MM. Considering that the presence of somatic mutations could influence risk stratification and therapeutic approaches of patients with MM, sensitive detection of these mutations at diagnosis is essential for optimal management of MM. Full article

Plasmacytoma is a neoplastic disorder originating from plasma cells, with bone and soft tissue being common sites of manifestation. This report presents the clinical and radiological findings of a 65-year-old female patient who presented with an exophytic lesion in the upper right lateral incisor region. The lesion appeared as a unilocular radiotransparent area in imaging tests. Following an excisional biopsy, histological and immunohistochemical evaluations confirmed the presence of mature plasmacellular elements and small infiltrates of B and T lymphocytes. The patient did not exhibit systemic manifestations of multiple myeloma. Surgical intervention, in the form of enucleation of the lesion combined with root canal treatment and apicoectomy, was performed. This case underscores the rare occurrence of plasmacytoma in the jaw region and highlights the importance of surgical management in cases where structural damage or functional impairment is present. Further research on novel treatment approaches is also mentioned, including targeted therapies, immunomodulatory agents, and monoclonal antibodies. The patient is currently under the care of a hematologist for further investigation and the choice of the most appropriate therapy. Full article