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Simple Summary: Whole-body magnetic resonance imaging (WB-MRI) is increasingly being used to evaluate a wider range of patients with different types of cancer and for cancer screening. To standardize acquisition, interpretation, and reporting, three WB-MRI reporting and data systems (RADSs) have been recently introduced: METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P), Myeloma Response Assessment and Diagnosis System (MY-RADS), and Oncologically Relevant Findings Reporting and Data System (ONCO-RADS). The aim of this review is to provide a summary of the scientific evidence that has emerged so far regarding the clinical utility of WB-MRI RADSs. Although preliminary studies have demonstrated promising and consistent results regarding the prognostic value and reliability of WB-MRI RADSs, additional research is necessary, particularly for ONCO-RADS and inter-reader agreement for MY-RADS. Larger, prospective, multi-center studies are required to confirm and extend these encouraging initial findings. Whole-body magnetic resonance imaging (WB-MRI) is being employed with increasing frequency to evaluate a broader spectrum of patients with diverse types of cancer and for cancer screening purposes. While clinical guidelines support its use, a standardized radiological approach is still lacking. To improve consistency in the acquisition, interpretation, and reporting of WB-MRI examinations, three reporting and data systems (RADSs) have been recently suggested: METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P), Myeloma Response Assessment and Diagnosis System (MY-RADS), and Oncologically Relevant Findings Reporting and Data System (ONCO-RADS). MET-RADS-P was developed to stage and monitor men with advanced prostate cancer using WB-MRI. It has emerged as a reliable imaging biomarker for predicting metastatic disease progression and assessing treatment response. MY-RADS was developed to stage and monitor patients with multiple myeloma using WB-MRI, emerging as a prognostic imaging biomarker. However, the evidence regarding inter-reader agreement for MY-RADS is currently limited. ONCO-RADS was developed to standardize the use of WB-MRI for cancer screening in individuals with cancer predisposition syndromes and in the general population. While initial findings are promising, the evidence supporting its use remains limited. To further validate and expand upon these promising preliminary findings, additional large-scale, prospective, multicenter studies are necessary. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to determine if there are differences in outcome for patients diagnosed with multiple myeloma in a rural setting compared to a metropolitan setting and which factors influence these outcomes. Design: Retrospective cohort study. Setting: Illawarra Shoalhaven Local Health District. Participant s : A total of 391 patients diagnosed with multiple myeloma between 2000 and 2022. Main outcome measures: Treatment and survival outcomes of these patients. Results: Patients being treated in a rural cancer care centre had lower overall survival compared to those treated at a metropolitan cancer care centre (median OS = 44.4 months vs. 80.2 months, p = 0.002), despite access to similar treatments by the same group of haematologists. There was a significantly higher rate of upfront autologous transplantation (38% vs. 20%, p = 0.001) and higher rate of inclusion in clinical trials (16% vs. 7%, p = 0.021) in patients treated at a metropolitan cancer care centre compared to the rural cancer care centre. Conclusions: Multiple myeloma patients treated at a rural centre had shorter survival compared to patients treated at a metropolitan centre, and this may be related to lower rates of autologous transplantation and inclusion in clinical trials. [ABSTRACT FROM AUTHOR]

Background Interferences on chemistry and immunoassay results due to paraproteinemia may lead to erroneous diagnoses and treatment. Such interferences are difficult to recognize and even more difficult to deal with. This report describes 1 such case where multiple measurands were affected and how the interferant was overcome. Case Report Paraproteins present in an immunoglobulin (Ig)G-lambda multiple myeloma specimen interfered with results of total bilirubin, direct bilirubin, inorganic phosphate, iron, ferritin, and total thyroxine measured on 3 platforms: AU5800, Alinity ci, and cobas pure. Repeat testing upon dilution with normal saline or deproteinization by polyethylene glycol precipitation gave unsatisfactory results on some or all the affected measurands. Repeat testing after dilution of the interferant serum with a healthy serum corrected the anomalous results for all the affected measurands. Conclusion Dilution of paraproteinemic serum with a healthy serum of known concentrations appears to be the most suitable method to negate the effects of paraproteinemic interferences. [ABSTRACT FROM AUTHOR]

Introduction: Patients frequently present with renal impairment that does not fit the criteria for acute kidney injury or chronic kidney disease. This condition, known as rapidly progressive renal failure (RPRF), encompasses a diverse range of clinical syndromes characterized by the progressive renal impairment over days to weeks. Case Report: We present a case of a 37-year-old male with a short history of uremic symptoms and decreased urine output with no significant history or examination findings except pallor. The patient had a creatinine of 1.6 mg/dL in April 2022, rising to 4.4 mg/dL, then 11.6 mg/dL during May, 17.6 mg/dL in June, presented to us with a creatinine of 24.6 mg/dL, with normal kidney size and corticomedullary differentiation (CMD). Beta-2-microglobulin was elevated, and renal biopsy showed features suggestive of multiple myeloma (MM). Atypical appearing tubular casts showing 3+ patternless staining for kappa light chains and negativity for lambda light chains were observed. The patient was started on chemotherapy for MM, and renal function was gradually improving. Conclusion: Renal failure as the sole presentation of MM is rare, especially in young adults. This case emphasizes an atypical RPRF, particularly given the patient's young age. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) is a blood cancer which classically has a prolonged course of remissions and relapses. Several new highly efficacious medications have been developed for MM in recent years, including some that utilize the body's own immune cells to control the cancer. Alongside the development of these new medications has been the evolution of tests to track small amounts of (measurable) residual disease (MRD). Several MRD tests can now find and track as little as 1 residual cancer cell in 1 million in certain cases. Having no detectable MRD has been independently associated with improved cancer control and longer survival—here, we review how these tests might be used as a companion to new immune therapies for MM. Several novel T-cell-based therapies have recently become available for multiple myeloma (MM). These T-cell redirecting therapies (TRTs) include chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BiAbs). In both clinical trial and real-world data, these therapies have demonstrated high rates of deep clinical response, and some are now approved for second-line treatment for relapsed MM. The deep and sustained clinical responses these therapies are capable of inducing will require sophisticated response monitoring to provide meaningful information for patient care. Obtaining measurable residual disease (MRD) negativity has been validated as an independent positive prognostic marker for progression-free survival (PFS) and overall survival (OS) in both newly diagnosed and relapsed refractory patients with multiple myeloma. Assessment for MRD negativity was performed in all of the trials for FDA-approved TRT. Here, we summarize pertinent data for MRD assessment following TRT in MM and provide a rationale and structured framework for conducting MRD testing post TRT. [ABSTRACT FROM AUTHOR]

This case report addresses the author's experience providing nursing care to a 37-year-old patient diagnosed with multiple myeloma requiring regular renal dialysis due to disease progression who received autologous stem cell transplantation. The patient was diagnosed with cancer in young adulthood and, as a father figure, faced various psychological issues associated with the unexpected challenges encountered during their treatment phase. Psychosocial health, which is closely associated with quality of life in patients with cancer, has gained increasing attention in recent years. The limited research published on the subject of fathers diagnosed with cancer encouraged the author to detail her experience with this case. The care period was from August 5th to August 19th, 2022. During the care period, the Gordons's 11 functional health assessment was applied, with potentially severe infections, coping disorders, anxiety, potential risk of injury existing or potential nutritional deficiencies, oral mucosal changes, and diarrhea identified as the primary health problems of concern. Nursing interventions applied included providing protective isolation measures to prevent post-transplant infection, helping the patient learn effective ways to cope with emotional distress, and providing comprehensive follow-up care information and health education to alleviate the anxiety associated with hospital discharge and life after discharge. The challenges of providing nursing care to adolescent and young adult patients differ significantly from those faced in the care of either elderly or pediatric patients. Furthermore, although extensive research has been conducted on mothers diagnosed with cancer, little research has addressed the impact on the paternal role when fathers are diagnosed with cancer, with limited information available regarding their psychological concerns and issues or the impact on family dynamics. The author hopes this case care experience offers an insightful reference and guide for nursing practice that contributes to a better understanding of the psychological aspects of young adult fathers diagnosed with cancer and facilitates more appropriate care in clinical settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Induction regimens using 4-drugs for patients with newly diagnosed multiple myeloma have shown impressive results in multiple trials. However, trials of 4-drug regimens typically use a 3-drug regimen as their comparator, which limits our ability to determine whether the benefit is from the specific combination of drugs or just the addition of more agents. We performed a meta-analysis to compare all trials that compared 4-drug to 3-drug regimens and found that the addition of an anti-CD38 antibody (daratumumab or isatuximab) resulted in improved responses, while 4-drug regimens without an anti-CD38 antibody performed similarly to 3-drug regimens. While the addition of an anti-CD38 antibody led to increased adverse effects, these were predominantly mild and easily managed. These data suggest that an anti-CD38 antibody should be part of all 4-drug induction regimens for newly diagnosed myeloma patients. The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Although liquid biopsy has emerged as a viable substitute, bone marrow (BM) is still the gold standard for the diagnosis and follow-up of patients with multiple myeloma (MM) and smouldering MM (SMM). The potential involvement of circulating MM cells (CMMCs), counted via CELLSEARCH®, in monitoring disease dynamics was assessed by measuring them during treatment and correlating the results with the prognoses of the patients. For MM and SMM patients, the median numbers of CMMCs counted at diagnosis were 349 (1 to 39,940) and 327 (range 22–2463), respectively. Among SMM patients, higher CMMCs were associated with a greater propensity to evolve (p = 0.042). The CMMC counts in the MM patients showed a significant correlation (p < 0.04) with serum albumin and monoclonal component concentration. Under therapy, CMMCs were consistently detectable in 15/40 patients (coMMstant = 1), and correlated with lower responses (p = 0.04) and survival probability (p = 0.047), suggesting that CMMC persistence is linked to poor prognoses. In recent years, liquid biopsy has emerged as a promising alternative to the bone marrow (BM) examination, since it is a minimally invasive technique allowing serial monitoring. Circulating multiple myeloma cells (CMMCs) enumerated using CELLSEARCH® were correlated with patients' prognosis and measured under treatment to assess their role in monitoring disease dynamics. Forty-four MM and seven smouldering MM (SMM) patients were studied. The CMMC medians at diagnosis were 349 (1 to 39,940) and 327 (range 22–2463) for MM and SMM, respectively. In the MM patients, the CMMC count was correlated with serum albumin, calcium, β2-microglobulin, and monoclonal components (p < 0.04). Under therapy, the CMMCs were consistently detectable in 15/40 patients (coMMstant = 1) and were undetectable or decreasing in 25/40 patients (coMMstant = 0). High-quality response rates were lower in the coMMstant = 1 group (p = 0.04), with a 7.8-fold higher risk of death (p = 0.039), suggesting that continuous CMMC release is correlated with poor responses. In four MM patients, a single-cell DNA sequencing analysis on residual CMMCs confirmed the genomic pattern of the aberrations observed in the BM samples, also highlighting the presence of emerging clones. The CMMC kinetics during treatment were used to separate the patients into two subgroups based on the coMMstant index, with different responses and survival probabilities, providing evidence that CMMC persistence is associated with a poor disease course. [ABSTRACT FROM AUTHOR]

Introduction: Limited data exist on interphase fluorescent in situ hybridization (iFISH)-based survival outcomes in newly diagnosed multiple myeloma (NDMM) from India. Objectives: To study the demographics and iFISH-based survival outcomes in NDMM patients treated with proteasome inhibitors from a community-based cancer setup. Materials and Methods: We reviewed the records of 25 patients treated with proteasome inhibitors between June 2017 and April 2023 using five high-risk (HR) iFISH markers based on mSMART 3.0. Results: The median age was 60 years (range 34–87). HR iFISH was detected in 12 (48%) patients. With a median follow-up of 27 months, the overall response at the last follow-up was 80% (very good partial response - 52%, complete remission - 20%, and partial response - 8%), with 8 (32%) relapses. Twenty (80%) patients remain alive, with five deaths in HR (sepsis [ n = 3]). The 2.5-year overall survival in HR and standard risk was 55.6% ± 15.2% and 100% (P = 0.01), and event-free survival was 32.4% ± 16.5% and 77.8% ± 13.8% (P = 0.02), respectively. Conclusions: Using limited iFISH HR markers helps in the early and effective stratification of NDMM in the real world. Sepsis remains an important cause of mortality in an Indian setup. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy is a prevalent complication in plasma cell disorders, posing significant diagnostic and therapeutic challenges. This study presents three cases initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Despite initial symptom regression post-immunomodulatory treatment, the patients exhibited progressive neurological deficits. Advanced laboratory evaluation confirmed monoclonal protein presence, yet traditional diagnostic methods, including bone marrow biopsy and flow cytometry, yielded normal results. Utilizing 18F-FDG PET/CT, we identified multiple hypermetabolic vertebral lesions, which upon biopsy, confirmed the diagnosis of plasmacytoma. Our findings underscore the utility of PET/CT as a reliable diagnostic tool for monoclonal gammopathy associated neuropathy, advocating for its consideration in cases with equivocal diagnosis. When the diagnosis is in doubt, biopsy of a lesion may facilitate early and accurate diagnosis, potentially influencing treatment strategies and patient outcomes. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a clonal proliferation of plasma cells in the bone marrow, with criteria including bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma with myeloma-defining events. Solitary plasmacytoma (SP) represents a singular clonal plasma cell lesion without myeloma-defining events, while extramedullary disease (EMD) is an aggressive form of MM characterized by independent growth outside the bone marrow microenvironment. We present a unique case of a 64-year-old patient with bilateral testicular plasmacytoma anteceding the development of Immunoglobulin G (IgG) kappa-type MM, featuring extramedullary renal involvement. [ABSTRACT FROM AUTHOR]

Patients living with multiple myeloma (MM) have a substantial disease burden and face multiple barriers to care. Building upon our previous research using mixed methods, this focus group research aimed to identify patients' priorities regarding specific social and identity-related needs, map these prioritized needs to the disease journey, and describe patient-generated ideas to improve patient support. Participants noted that patients with MM need a range of emotional, social, and financial support throughout the disease journey. They identified initial MM diagnosis and treatment adherence as two critical points in the MM journey where patients need the most support and assistance. The findings of this research suggest that overall, patients with MM need comprehensive support, ideally from a multidisciplinary team consisting of health care providers, patient advocates, social workers, and psychologists to help patients understand their disease and treatment options, make informed treatment decisions, adhere to treatment, and ultimately reduce their disease burden and improve outcomes. This research revealed that patients with MM need varying types and levels of support, with the most common needs including information on disease and treatment, connections to financial resources and support systems, assistance with navigating insurance options, and transportation and logistical support for medical appointments. [ABSTRACT FROM AUTHOR]

Background A substantial number of patients with multiple myeloma (MM) who have bone destruction are initially admitted into the orthopedic service at the hospital. However, routine laboratory testing usually fails to identify these patients, thus delaying optimal therapy. Therefore, there is a clear medical need for early diagnosis of MM in these patients. Methods Between 2019 and 2021, 42 patients receiving treatment for orthopedic conditions had normal hemoglobin (Hb), total protein (TP), albumin (ALB), creatinine (CREA), and blood calcium (Ca) levels before their surgical procedure(s) but were subsequently pathologically confirmed to have MM, based on their presenting orthopedic symptoms. During the same period, 52 patients with orthopedic conditions were pathologically excluded from the diagnosis of MM and were recruited into our control group. Serum free light chain (sFLC) testing was performed in 94 consecutive patients in the orthopedic service using Siemens N Latex FLC kits. The levels of Hb, TP, ALB, CREA, and Ca were also measured. All 42 patients with MM were divided into group A (n = 25: κ proliferation) and group B (n = 17: λ proliferation) by the pathology department. Results There were no significant differences in levels of Hb, TP, ALB, CREA, and Ca between group A and group B and the control group. However, the sFLC κ/λ ratio of group A and B was also significantly different from that of the control group (P <.001). The results of serum immunofixation electrophoresis (IFE) testing demonstrated negative results in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B. Conclusions Some patients with orthopedic conditions who do not have typical MM laboratory results, such as those with abnormal Hb, TP, ALB, CREA, and Ca levels before their operation(s), actually have MM. MM should be highly suspected in patients with unexplained bone lesions and with an abnormal sFLC κ/λ ratio. Further tissue or bone marrow biopsy is needed in these patients even if serum and urine IFE results are negative and light chain ratio is normal. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) represents the second most common hematological malignancy, but its diagnosis can be significantly delayed since symptoms are not specific and, mainly in the older population, alternate diagnoses can mimic MM. Bone marrow biopsy (evaluating the amount of proliferating myeloma cells) remains an essential procedure, but several imaging methods such as whole-body low-dose computed tomography, positron emission tomography or whole-body magnetic resonance have become crucial for the diagnosis and staging of MM, and are also taking on a prognostic role. MM is a clinically and biologically heterogeneous disease; therefore, with the aim to identify patients with different outcomes, some risk models such as ISS, R-ISS or R2-ISS have been proposed over time. However, the most recent attempts have been to establish individualized patient risk, integrating clinical, genomic and therapeutic data in order to personalize treatment and avoid overtreatment and toxicities. The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment. Moreover, he must deal not only with organ issues related to MM such as bone disease, renal failure or neurological disease but also with adverse events, often very serious, related to novel therapies, particularly new generation immunotherapies such as CAR T cell therapy and bispecific antibodies. In this review, we provide an overview on the newer MM diagnostic and monitoring strategies and on the main side effects of MM therapies, focusing on adverse events occurring during treatment with CAR T cells and bispecific antibodies. [ABSTRACT FROM AUTHOR]

Sinonasal system malignancies are rare, constituting only 1% of all malignancies and less than 5% of head and neck malignancies. The common form of plasma cell dyscrasias is called multiple myeloma (MM), and the localized forms are called solitary bone plasmacytoma and extramedullary plasmacytoma (EMP). EMP constitutes 3-4% of malignant plasma cell dyscrasias and 1% of all head and neck tumors. 90% of EMP cases occur in the head and neck region, because the nasal and paranasal sinus regions are rich in plasma cells at around 75%. This study aims to present two different cases of plasma cell tumors presenting in the paranasal region. Based on the imaging studies, the first case is seen to have been diagnosed as MM due to bone marrow involvement and to have received systemic chemotherapy treatment, whereas the second case is seen to have undergone endoscopic total excision of the lesion due to the absence of systemic involvement. In the first case, MM was considered to have gone into remission in the sixth month after chemotherapy; however, the patient died one year after diagnosis. In the second case, no recurrence was detected during the fifth year postoperative follow-up. As a result, patients who show sinonasal symptoms should be examined in detail. [ABSTRACT FROM AUTHOR]

This paper introduces two cases of multiple myeloma, COVID-19 infection during autologous stem cell transplantation, the treatment process, and different results of the two patients, which provides a reference for how to carry out ASCT safely during the COVID-19 normalization stage. [ABSTRACT FROM AUTHOR]

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PURPOSE Little is known about the role of social determinants of health (SDOH) in the utilization of novel treatments among patients with newly diagnosed multiple myeloma (NDMM). METHODS This retrospective cohort study used Taussig Cancer Center's Myeloma Patient Registry to identify adults with NDMM between January 1, 2017, and December 31, 2021. Electronic health records data captured treatment with (1) triplet or quadruplet regimen and (2) lenalidomide during the first year after NDMM, and (3) stem-cell transplant (SCT) through December 31, 2022. Multivariable logistic regression models examined associations of demographic/clinical characteristics and SDOH with care patterns. RESULTS We identified 569 patients with median age at diagnosis of 66 years (IQR, 59-73); 55% were male, 76% White, 23% Black, 1.1% other races, insured by Medicare (51%), private payer (38%), Medicaid (8.3%), and self-pay/other (1.8%). In the multivariable models, self-pay/other payers (adjusted odds ratio [AOR], 0.15 [95% CI, 0.03 to 0.54]) was associated with lower odds of triplet or quadruplet regimen, compared with Medicare. Private insurance (AOR, 0.48 [95% CI, 0.27 to 0.86]) and self-pay/other payers (AOR, 0.16 [95% CI, 0.04 to 0.74]) had lower odds of lenalidomide. Black patients (v White; AOR, 0.47 [95% CI, 0.26 to 0.85]) and patients treated at regional hospitals (v Taussig Cancer Center; AOR, 0.27 [95% CI, 0.12 to 0.57]) had lower odds of SCT. The odds of receiving triplet or quadruplet regimen, lenalidomide, and SCT also varied by the year of NDMM. CONCLUSION Care for NDMM varied based on race, insurance type, year of diagnosis, and treatment facility. It may be useful to examine the impact of insurance-related characteristics and recent policy initiatives on care disparities. [ABSTRACT FROM AUTHOR]

Multiple myeloma is the most frequent malignant monoclonal gammopathy characterized by plasma cell proliferation and monoclonal M-protein production as consequence. Gold standard for diagnosis of monoclonal gammopathies are urinary and serum electrophoretic tehniques. Until recently, multiple myeloma was defined and diagnosed by damaged organs, particularly through hypercalcemia, renal failure, anemia and bone lesions. International Myeloma Working Group revised the criteria for multiple myeloma diagnosis by adding three biomarkers of malignancy effective in early recognition of patients who have not developed permanent organ damage. Those biomarkers are clonal proliferation of plasmocytes in bone marrow ≥60%, ratio of serum free light chains ≥100 with the included serum free light chain having an absolute concentration >100 mg/L and more than one osseus change on magnetic resonance imaging. This enables early beginning of an effective therapy in high-risk patients. Objective of the research was to evaluate the impact of serum free light chain ratio, total proteins and serum protein electrophoresis, as an initial panel for diagnosis of multiple myeloma, on beta 2 microglobulin and albumin, as markers of tumor burden and prognosis, at baseline and the differences between analyzed parameters in study and control group. Design of the research was a cross sectional study/study of prevalence conducted in the period of two months. Study group consisted of 7 newly diagnosed patients, before treatment, at 18 to 80 years of age. Control group consisted of 10 healthy individuals. All participants were included in the research after prior written informed consent. The concentration of serum free light chains (N-Latex Free Light Chains) and beta 2 microglobulin were determined nephelometrically on the plasma protein analyzer BN proSpec-Siemens (Siemens Medical Systems). The ratio was calculated by the analyzer software. Any result of the ratio <0.26 and >1.65 was considered pathological, depending on the involved component. Significance was determined at p<0.05. Electrophoretic examination of serum proteins was performed by gradient (4-22%) sodium dodecyl sulfate polyacrylamide gel electrophoresis. The confirmation of the diagnosis was obtained from the hospital information system of the Hematology Clinic in Skopje. For R = 0,99 and p<0,01 we found a high correlation between beta 2 microglobulin and serum free light chain ratio, total proteins and serum protein electrophoresis at baseline. For R = 0,98 and p<0,05 there was a high correlation between albumin and serum free light chain ratio, total proteins and protein electrophoresis in serum at baseline. Serum free light chain ratio results were significantly higher in study group p<0,05 (p=0,01). Beta 2 microglobulin results were significantly higher in study group p<0,01 (p=0,001). In conclusion, the results of the study confirmed the association between serum free light chain ratio and beta 2 microglobulin as an indicator of tumor burden in multiple myeloma, as well as with the biological characteristics of myeloma cells. [ABSTRACT FROM AUTHOR]

Objective: Calprotectin (CLP), S100A6, and high mobility group nucleosome-binding protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to investigate the relationships of serum CLP, S100A6, and HMGN1 levels with the clinical and laboratory findings of patients with multiple myeloma (MM) and their roles in the pathogenesis of MM. Materials and Methods: We measured the serum CLP, S100A6, and HMGN1 levels of 55 newly diagnosed patients and 32 healthy controls using the sandwich enzyme-linked immunosorbent assay method. The medical records of the patients were also reviewed. Results: Serum CLP, S100A6, and HMGN1 levels were significantly decreased in MM patients compared to the control group (p=0.012, p=0.001, and p=0.030, respectively). Receiver operating characteristic analysis was used to determine diagnostic cut-off values for serum CLP, S100A6, and HMGN1 of <98 ng/mL (area under the curve [AUC]: 0.663, 95% confidence interval [CI]: 0.554-0.761, p=0.009), <1174.5 pg/mL (AUC: 0.706, 95% CI: 0.598-0.799, p=0.001), and <440.18 pg/mL (AUC: 0.640, 95% CI: 0.530-0.740, p=0.03), respectively. CLP levels were found to be statistically significantly higher in patients with light chain MM (91.58±22.57 ng/mL) compared to heavy chain MM (79.42±15.83 ng/mL) (p=0.03). A negative correlation was observed between CLP and M protein, immunoglobulin G, globulin, and beta-2 microglobulin (correlation coefficients: -0.361, -0.370, -0.279, -0.300, respectively; p=0.024, p=0.06, p=0.04, p=0.0033). Conclusion: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in patients with newly diagnosed MM compared to the control group. These results suggest that CLP may bind to the paraprotein produced by heavy chain MM in the blood, causing its blood levels to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in cases of MM. [ABSTRACT FROM AUTHOR]

Simple Summary: The cornerstone of successful treatment of hematologic diseases, including multiple myeloma (MM), is early diagnosis and establishing a prognosis for the patient. Therefore, it is necessary to identify sensitive and specific markers for this disease. Non-coding RNAs including miRNAs are increasingly being recognized as potential diagnostic, predictive, and prognostic markers. These molecules are non-coding, single-stranded RNAs that regulate the expression of many target genes involved in key biological processes, such as cell proliferation, differentiation, and apoptosis. This paper aims to identify the role of non-coding RNAs including miRNAs as potential markers for diagnosis and prognosis in patients with MM. Multiple myeloma (MM) is the second most common hematologic malignancy in the world and accounts for 15% of primary hemocytopathies, with an ever-increasing number of new cases. It is asymptomatic in 30% of instances; hence, the determination of highly sensitive and specific markers is necessary to make a proper diagnosis. In the last 20 years, miRNAs, involved in regulating the expression of genes responsible for cell proliferation and differentiation, including tumor cells, have been identified as potential diagnostic and prognostic markers. The main aim of the following review was to outline the role of miRNAs in the diagnosis and prognosis of MM, considering their role in the pathogenesis of the disease and identifying their target genes and pathways. For this purpose, publications dating from 2013–2023 have been reviewed. Based on the available data, it is concluded that non-coding RNAs including miRNAs could be potential markers in MM. Furthermore, they may serve as therapeutic targets for certain drugs. [ABSTRACT FROM AUTHOR]

The treatment of multiple myeloma has evolved significantly over the past few decades with the development of novel therapeutics. The introduction of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and high-dose chemotherapy followed by hematopoietic stem cell transplantation has led to improved response rates and survival outcomes. The use of bispecific antibodies and chimeric antigen receptor T-cell therapy is currently under study, and early results are showing promise. Although outcomes for patients with MM have improved with the development of new treatments, there remains a subset of patients with high-risk disease who have a particularly poor prognosis. Therefore, it is critical that future clinical trials focus on developing new therapies specifically for high-risk multiple myeloma. Here we review the literature and provide guidance on treating patients with multiple myeloma for practicing oncologists. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis of plasma cell neoplasms depends on the accurate quantification of plasma cells, traditionally done by immunohistochemical CD138 staining of bone marrow biopsies. Currently, there is no fully satisfactory reference method for this quantification. In our previous study, we compared the commonly used overview estimation method (method A) with a novel method for counting plasma cells in three representative areas (method B). Results showed comparable concordance parameters between the two methods. In this follow‐up study, we compared the previously evaluated methods with a digital analysis method (method C) that uses artificial intelligence in open‐source software, QuPath. Methods: Archived CD138 immunohistochemically stained trephine sections of bone marrow samples used in our previous study were used (n = 33). Reviewers selected three representative areas on each sample by taking images with a light microscope and camera. Digital analysis was performed using the positive cell detection function in QuPath. The entire process was repeated by each reviewer to test intraobserver concordance (concordance correlation coefficient [CCC]) in addition to interobserver concordance (intraclass correlation coefficient [ICC]). Results: Intraobserver concordance of method C showed strong agreement for all reviewers with the lowest CCC = 0.854. Interobserver concordance for method C using ICC was 0.909 and 0.949. This showed high interobserver agreement with significant differences between method C and previously assessed method A (ICC = 0.793 and 0.713) and method B (ICC = 0.657 and 0.658). Conclusion: We were able to successfully count CD138‐positive plasma cells in bone marrow biopsies using artificial intelligence. This method is superior to both manual counting and overview estimation, regardless of tumour load. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma is a hematologic neoplasm caused by abnormalities of plasma cells. Although cytogenetic-based risk stratifications are in clinical use, the role of genomic mutations in prognosis assessment is incompletely understood. Moreover, the sample source for molecular testing is a matter of debate, with recent data pointing out that seeking for mutations in plasma cells would increase the yield. We hereby compared both cytogenetic abnormalities and mutations detected by NGS in bulk bone marrow samples and CD138+ enriched plasma cells from patients diagnosed with multiple myeloma. We performed a FISH analysis, and then we used NGS to assess mutations in NRAS, KRAS, BRAF, and TP53 in the plasma cells and bulk bone marrow samples. The NGS data showed that the sequencing of the CD138+ plasma cells provided a more sensitive approach by identifying more variants in BRAF, KRAS, and TP53 compared to bulk marrow sequencing. 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. [ABSTRACT FROM AUTHOR]

Multiple myeloma associated with bleeding events secondary to von Willebrand syndrome is underdiagnosed. The management of this entity is highly complex, and aims to control the hemorrhagic syndrome and reduce plasma viscosity with plasmapheresis and multiple myeloma-specific treatment. The authors report the rare case of a young patient with high-risk multiple myeloma complicated by hyperviscosity syndrome and presenting an acquired von Willebrand syndrome with hemorrhagic manifestations, requiring urgent therapeutic management to save the patient's life. [ABSTRACT FROM AUTHOR]

Multiple myeloma is the third most common type of blood cancer, after leukemia and non-Hodgkin's lymphoma. It represents a complex medical challenge, and early diagnosis and appropriate treatment can improve the patient's prognosis and quality of life. The diagnosis of multiple myeloma is made with the help of serum protein electrophoresis, which shows the excess of a certain type of antibodies that is highlighted by a peak, called "monoclonal peak". The proteinogram changes in multiple myeloma are strongly expressed and characteristic, having diagnostic value, and, for greater certainty of the diagnosis, blood tests will be corroborated with bone radiography, computed tomography and marrow biopsy. [ABSTRACT FROM AUTHOR]

Introduction: Multiple myeloma is a type of plasma cell dyscrasia, which causes clonal proliferation of plasma cells and deposition in various organ systems. At presentation, 50% of patients with multiple myeloma have kidney dysfunction, which is considered a poor prognostic indicator. Data on the histopathological manifestations of multiple myeloma are sparse. Objective: To look at the kidney histopathological lesions in patients with the clinical diagnosis of multiple myeloma. Materials and Methods: A retrospective analysis of all kidney biopsies in patients with the clinical diagnosis of multiple myeloma was performed from June 1, 2020 to May 30, 2022, from three tertiary care nephrology referral centers. Results: A total of 61 patients with multiple myeloma and biopsy-proven kidney involvement were included in the study. The mean age at presentation was 55.39 ± 11.91 years, with male predominance (male to female ratio -1.6:1). The most common lesion on kidney biopsy was myeloma cast nephropathy (72.1%), followed by light chain deposition disease (21.3%) and AL amyloidosis (18%). About 26% of patients had dual lesions on kidney biopsy, 3% had three types of lesions on kidney biopsy In 48% of patients, the diagnosis of multiple myeloma was made only after the kidney biopsy. Conclusion: Patients with multiple myeloma and kidney involvement should be biopsied as the type of histopathological lesion influences the treatment options and prognosis. [ABSTRACT FROM AUTHOR]

Introduction: The complexity of treatment and extended therapy duration associated with bone marrow transplantation directly affect the psychological well-being of the patients, create anxiety, and reduce their quality of life. The aim of our study was to evaluate the quality of life of patients admitted to the bone marrow transplantation unit. Methods: This prospective and descriptive study was conducted between January and June 2021 in an adult BMT unit in Turkey. The sociodemographic characteristics of the patients were recorded. The patient's quality of life was measured twice using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) scale at the beginning of the study and 30 days later. SPSS 15 was used for the analysis. Results: A total of 40 patients were included in the study. The mean age was 46 years. Most of the patients were diagnosed with multiple myeloma and 58% had at least one comorbid disease. Most of the patients (78%) were receiving myeloablative therapy. High dose melphalan regimen was the most commonly applied regimen (25%). Thrombocytopenia was the most common side effect (14%). Although there was no change in the quality of life, it was found that the social/family well-being scores increased (p < 0.05). Conclusions: In our study, it was observed that the number of comorbid diseases was higher in patients with bone marrow transplantation. The incidence of side effects may be high in these patients. We believe that clinical pharmacists have an important role in monitoring adverse effects and improving the quality of life in bone marrow transplantation units. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients who are diagnosed with multiple myeloma are given an initial sequence of treatments that usually, for those who are young and fit enough, includes high-dose melphalan followed by autologous stem cell transplantation. This has contributed to the improvement in survival seen over the past 30 years. However, high-dose melphalan has significant limitations, including short-term side effects and longer-term issues such as an increased risk of developing secondary hematologic malignancies including leukemia. There are now numerous highly efficacious combination regimens for initial treatment that result in increasingly large proportions of patients achieving deep responses with no evidence of minimal residual disease. Moreover, large, randomized studies using these regimens have shown no benefit in overall survival after receiving high-dose melphalan with stem cell transplantation. There is thus a growing rationale for selected eligible patients to defer receiving high-dose melphalan and stem cell transplantation until potentially needed in a subsequent line of treatment. The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study we examined the cytogenetic profile of 1087 patients with plasma cell neoplasms (PCNs) at different stages, including monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Our study demonstrated that >95% of patients exhibited at least one cytogenetic abnormality detected by FISH tests and/or chromosomal analysis. The frequency of IGH::CCND1 rearrangement was 26% in this cohort, but with no apparent differences across races, ages, or disease groups. Almost all cases with abnormal karyotypes presented a complex or composite karyotype, with most featuring five or more chromosomal abnormalities, and chromosome 1 structural abnormalities were the most prevalent (65%). The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM. Elevated frequencies of high-risk cytogenetics (59%) and the presence of subclones (48%) were particularly notable in RRMM cases. The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the quantification of circulating clonal plasma cells (cCPCs) in peripheral blood using flow cytometry could be used as a prognostic predictor of poor outcome in multiple myeloma (MM). Methods: In 66 newly diagnosed MM, cCPCs were quantified (cCPC%) and analysed for association with outcome and survival. Single‐tube combined surface (CD45/CD19/CD138/CD38/CD56/CD27/CD81 as per availability) and cytoplasmic (kappa/lambda) staining was done using pre‐titrated volumes of antibodies. In 26 patients, repeat cCPC% was assessed post‐induction therapy. For association studies, treatment response has been taken as good (VGPR and above) and poor (PR and below). All statistical analyses were performed with SPSS software version 16.0. Results: There was no significant association between cCPC% at baseline with staging (p = 0.43), β2‐microglobulin (p = 0.27) and albumin (p = 0.08). There was a significant difference between the pre‐induction and post‐induction cCPC% (p = 0.0001). The patients were segregated using a cut‐off of ≥0.197 and <0.197 based on the median values of baseline cCPC%. The post‐induction outcome was available for 47 patients among whom 33 (70%) had VGPR and above. There was a significant association between higher cCPC% at baseline with poor treatment response (p = 0.008). The median OS in the study patients was 42 (CI 28.14–43.03) months and the median PFS was 39 (CI 28.49–49.04) months. Higher cCPC% showed a lower median PFS (30 vs. 39 months) and OS (35 vs. 41 months) compared to lower cCPC% though it was not statistically significant. Conclusion: Flow cytometric baseline cCPC% in newly diagnosed MM was associated with poor treatment response and survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Clinical trials (CTs) may not always reflect real-world medical practice, particularly in non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients due to stringent recruitment criteria. Our objective was to assess exclusion rates, reasons, and survival outcomes for NTE NDMM patients in and out of CTs. Roughly 50% did not meet eligibility criteria, mainly due to comorbidities, poor ECOG-PS, or renal failure. CT participation correlated with higher overall response rates (ORRs), improved progression-free survival (PFS) and overall survival (OS), especially in recent years. A slight PFS extension associated with a substantial improvement in OS in CT patients suggested a selection bias. Excluded patients did not experience improved survival, with the median OS remaining unchanged from 2003 to 2017. These findings emphasize that CT participants may not fully represent the wider NDMM population in real-world clinical practice. It is essential to exercise caution when applying CT results to routine care settings, recognizing the limitations of generalization. The proportion of non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients excluded from clinical trials (CTs) and their prognosis is unknown. CT results may not be generalizable to real-world practice due to strict recruitment criteria. We analyzed causes of NTE-NDMM patient exclusion form CTs and their outcomes. A total of 211 NTE-NDMM patients were included. They were divided into three periods: 2003–2007, 2008–2012, and 2013–2017. Overall, 50% received non-trial treatment (NCT), while 50% participated in a CT (20% control group (CG) and 30% experimental group (EG)). Main causes for exclusion from CTs were comorbidities, ECOG > 2, and renal insufficiency. In the first two periods, the CR rate was similar regardless of treatment type, but in the last period, the EG group showed improved CR. Median PFS was similar in the first two periods, with a benefit seen only in the EG in the last period. The median OS was significantly longer in CT-included patients compared to NCT group in the last two periods. Conclusions: The presence of comorbidities and worsened ECOG were the main reasons for CT exclusion. Patients included in CTs had a longer OS than NCT. This OS benefit may be influenced by a selection bias, making it challenging to generalize CT results to real clinical practice. [ABSTRACT FROM AUTHOR]

Objective The acid/molybdate assay performed on the Beckman Coulter AU5821 could be subject to paraprotein interference, which potentially results in spurious hyperphosphatemia. We attempted to find a reliable solution to eliminate paraprotein interference in laboratory test results and discuss the causes of paraprotein interference. Methods We observed 50 multiple myeloma patients with serum paraproteins. We used the trichloroacetic acid (TCA) deproteinizing method to confirm that paraproteins indeed interfered with phosphate detection in the serum acid/molybdate assay. Furthermore, we used the dry chemical method (Vitros 5.1 FS, Johnson) and deionized water (H2O), normal saline (NS), and healthy human serum as alternative diluents. We assessed the clinical acceptability of the 4 methods by evaluating a bias percentage (bias%) lower than 10% under the premise of TCA treatment as a serum phosphate reference method. Results In total, comparing the results of the TCA treatment on the Beckman Coulter AU5821, 3/50 (6%) multiple myeloma patients exhibited phosphate pseudo-elevation (bias% >10%). Additionally, we found pseudo-hypophosphate only in immunoglobulin (Ig)G-kappa paraprotein samples, and all were above 50 g/L. The bias% between TCA and dry chemical method for the 3 patients was below 10%. The maximum acceptable dilutions for patient 22 were 8-fold H2O, 4-fold H2O , and 2-fold serum; those for patient 45 were 16-fold H2O, 16-fold H2O, and 2-fold serum. However, the bias% of patient 40 was beyond the acceptable range in all 3 dilution groups. Conclusion High concentrations of IgG kappa–type paraproteins are more likely to interfere with serum phosphorous detection. Both the TCA and dry chemical method can effectively eliminate paraprotein interference. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy is an innovative immunotherapy treatment for hematological malignancies. Some of the challenges in using this therapy are the development of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, immunosuppression, and hypogammaglobulinemia, which can be prolonged and significantly increase patients' risk of infection. Cytomegalovirus (CMV) is well known to cause disease and organ damage in immunocompromised hosts, increasing mortality and morbidity. We present a case of a 64-year-old man with multiple myeloma with a significant history of CMV infection that worsened after CAR T-cell therapy and became challenging to contain because of prolonged cytopenias, progression of myeloma, and development of other opportunistic infections. Strategies for prophylaxis, treatment, and maintenance of CMV infections in CAR T-cell therapy recipients are further warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: We conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor in myeloma patients. Despite significantly less frequent (p = 0.045) use of plerixafor in the etoposide group, the optimal collection rates (CD34+ cells ≥ 6 × 106/kg) were not significantly different between the two groups (p = 0.195). In addition, the rate of collected CD34+ cells of ≥ 8.0 × 106/kg was significantly higher in the etoposide group. Our results suggest that single-dose etoposide plus G-CSF may be a better option for patients who are expected to receive two or more transplantations. To explore the optimal mobilization for multiple myeloma (MM) patients, we conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor. After randomization, 27 patients in the etoposide group and 29 patients in the G-CSF alone group received mobilizations. Six (22.2%) patients in the etoposide group and 15 (51.7%) patients in the G-CSF alone group received plerixafor based on a peripheral blood CD34+ cell count of < 15/mm3 (p = 0.045). The median count of CD34+ cells collected was significantly higher in the etoposide group (9.5 × 106/kg vs. 7.9 × 106/kg; p = 0.018), but the optimal collection rate (CD34+ cells ≥ 6 × 106/kg) was not significantly different between the two groups (96.3% vs. 82.8%; p = 0.195). The rate of CD34+ cells collected of ≥ 8.0 × 106/kg was significantly higher in the etoposide group (77.8% vs. 44.8%; p = 0.025). Although the rates of grade II–IV thrombocytopenia (63.0% vs. 31.0%; p = 0.031) and grade I–IV nausea (14.8% vs. 0%; p = 0.048) were significantly higher in the etoposide group, the rates of adverse events were low in both groups, with no neutropenic fever or septic shock. Thus, both single-dose etoposide plus G-CSF and G-CSF alone with risk-adapted plerixafor were effective and safe, but the former may be the better option for patients who are expected to receive two or more transplantations. [ABSTRACT FROM AUTHOR]

Simple Summary: A precise mass spectrometry-based method was utilized to study proteins in the blood samples of over a thousand cancer patients. By accurately identifying and measuring protein levels using mass spectrometry, we focused on multiple myeloma and found potential markers for diagnosing the disease. These markers, including the complement C1 complex, JCHAIN, and CD5L, were combined in a prediction model with high accuracy for identifying multiple myeloma patients. Our findings could significantly impact cancer research by improving diagnostic tools. Mass spectrometry based on data-independent acquisition (DIA) has developed into a powerful quantitative tool with a variety of implications, including precision medicine. Combined with stable isotope recombinant protein standards, this strategy provides confident protein identification and precise quantification on an absolute scale. Here, we describe a comprehensive targeted proteomics approach to profile a pan-cancer cohort consisting of 1800 blood plasma samples representing 15 different cancer types. We successfully performed an absolute quantification of 253 proteins in multiplex. The assay had low intra-assay variability with a coefficient of variation below 20% (CV = 17.2%) for a total of 1013 peptides quantified across almost two thousand injections. This study identified a potential biomarker panel of seven protein targets for the diagnosis of multiple myeloma patients using differential expression analysis and machine learning. The combination of markers, including the complement C1 complex, JCHAIN, and CD5L, resulted in a prediction model with an AUC of 0.96 for the identification of multiple myeloma patients across various cancer patients. All these proteins are known to interact with immunoglobulins. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple myeloma (MM) have compromised immune systems due to the nature of the malignancy and anticancer treatments. This study aims to report the effects of Bortezomib-containing chemotherapy regimens on the severity and mortality of MM patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Method: This retrospective cohort study enrolled MM patients presenting with coronavirus disease 2019 (COVID-19) infection referred to Omid Hospital. Patients were divided into two groups based on whether they received any chemotherapy regimens containing Bortezomib within the last 90 days of admission or not. Clinical and laboratory characteristics, severity, and outcomes of both groups were reported and compared. Results: Among 48 patients with MM diagnosed with COVID-19 (63% male; median age 66), 33 received chemotherapy. The most common symptoms were fever, cough, and dyspnea, and there was no significant difference between the groups. Only D-dimer had a significant difference in laboratory tests (P = 0.03) and was higher in the chemotherapy group. There was no significant relationship between chemotherapy and severity (risk ratio (RR) = 1.17; 95% confidence interval (CI): 0.37 to 3.71; P = 0.79) or chemotherapy and mortality (RR = 1.00; 95% CI: 0.39 to 2.61; P = 0.99), even after adjusting for baseline C-reactive protein and white blood cell counts. Conclusion: Our study showed that receiving Bortezomib-containing chemotherapy regimens did not worsen the symptoms and prognosis of MM patients infected with COVID-19. However, further studies with larger sample sizes and longer follow-up times are needed to provide better evidence on this subject. [ABSTRACT FROM AUTHOR]

Background: The extramedullary disease usually occurs in the advanced stages of multiple myeloma and predicts poor survival. Commonly involved extramedullary sites in multiple myeloma include the nasal cavity, lymph nodes, lung, central nervous system, liver, spleen, skin, and orbit. Pleural effusion in multiple myeloma is unusual and rarely due to multiple myeloma itself. Myelomatous pleural effusions occur in less than 1% of cases of multiple myeloma. Material and methods: Eight patients were diagnosed with myelomatous pleural effusion in the Department of Medical Oncology at a tertiary cancer care center in India, during the 7-year period (2012 to 2018). Clinical presentation, diagnosis, treatment, and survival details were abstracted from medical records. Results: We report eight patients with myelomatous pleural effusion, constituting 0.45 % of all multiple myeloma cases treated during the study period. Five out of the eight patients were females with a median age of 58 years. Three patients had myelomatous pleural effusion at the time of initial diagnosis and five developed pleural effusion at disease progression. IgG was the common immunoglobulin subtype. The International staging system stage was stage I in one patient and stage III in seven patients. After the diagnosis of multiple myeloma, all patients developed myelomatous pleural effusion at a median of 7 months and all patients died within 2 weeks. Conclusion: Pleural effusions in multiple myeloma should be investigated to rule out myelomatous pleural effusion. Myelomatous pleural effusion is rare, having a poor prognostic outlook and an aggressive natural course. [ABSTRACT FROM AUTHOR]

Background Serum protein electrophoresis (SPEP) is an easy test separating serum proteins based on their physical and chemical properties. Although it is frequently used in the differential diagnosis of multiple myeloma and various chronic inflammatory diseases, its value in the etiologic classification of glomerular diseases has yet to be studied. Material and Methods We retrospectively reviewed the medical records of patients who underwent renal biopsy from 2008 to 2016 at our institution. We excluded patients who can not be classified as primary (PGn) or secondary glomerulonephritis (SGn). Univariate and multivariate logistic regression analyses were performed for the prediction of SGn. Results Four hundred thirty-two patients were included in the study. Of those, 57.9% had PGn. Rheumatological diseases, malignancies, and infections were the most common etiologic causes of SGn, accounting for nearly 75%. Univariate analysis revealed that alpha-1 (α1), gamma (Ɣ), and albumin fractions significantly differ between PGn and SGn groups. ROC curve analysis determined the cut-off value of (α1*Ɣ)/albumin ratio as 1.48. Multivariate analysis revealed that total serum protein and (α1*Ɣ)/albumin ratio were significantly independent predictors for SGn (p = 0.020 and p < 0.001, respectively). Conclusions A ratio generated by multiplying α1 and Ɣ and dividing by albumin from SPEP, an easy, reliable, and cheap test, may help clinicians differentiate between PGn and SGn after validation in more extensive prospective studies. [ABSTRACT FROM AUTHOR]

A qualitative study of the experiences of patients who received autologous stem cell transplant (ASCT) for the treatment of multiple myeloma (MM) was conducted to better understand their MM disease journey, including first symptoms, diagnosis, ASCT, and recovery. Sixteen participants, including 12 patients with MM and 4 caregivers of patients with MM, were interviewed in focus group meetings. Pain, weakness, and bone pain were common first symptoms among patients. The MM diagnosis was often made by a hematologist or oncologist. Patients were referred to a specialized oncologist after diagnosis, who was the primary driver in making ASCT treatment decisions. Eight patients received their ASCT in the inpatient setting, with some having lengthy hospital stays; 4 received their ASCT in an outpatient setting with 3 eventually being hospitalized. The focus groups identified that patients and caregivers perceived various unmet needs and impacts on quality of life throughout their transplant journey. Educational resources and innovative therapies are needed to reduce the disease burden of MM and enhance the quality of life for both patients and their caregivers. [ABSTRACT FROM AUTHOR]

Simple Summary: In multiple myeloma, malignant plasma cells accumulate in the bone marrow. The symptoms and complications include osteolytic bone disease, anemia, reduced kidney function, immunosuppression, and induction of tumor-associated angiogenesis. Mesenchymal cells are important components of bone marrow niches; studying their dysfunctional activities reveals key features in myeloma pathogenies and improves therapies. We discovered that a subset of mesenchymal cells that express the receptor EDNRA are more prevalent in bone marrow areas infiltrated with tumor cells. In normal conditions, these cells are attached to blood vessels and mediate their functions; but in myeloma they seem to detach and accumulate in the interstitial marrow. The proportion of EDNRA-expressing cells and the expression of EDNRA in bone biopsies is low in premalignant stages and highest in high-risk myeloma patients. EDNRA could serve as a useful novel clinical biomarker of disease progression and dysfunctional bone marrow vasculature. Multiple myeloma (MM) induces dysfunctional bone marrow (BM) mesenchymal cells and neoangiogenesis. Pericytes and smooth muscle cells (SMCs) could detach from vessels and become cancer-associated fibroblasts. We found that the pericyte and SMC marker endothelin receptor type A (EDNRA) is overexpressed in whole MM bone biopsies; we sought to characterize its expression. EDNRA expression gradually increased with disease progression. High-risk MM patients had higher EDNRA expression than low-risk MM patients and EDNRA expression was highest in focal lesions. High EDNRA expression was associated with high expression of pericyte markers (e.g., RGS5, POSTN, and CD146) and the angiogenic marker FLT1. A single-cell analysis of unexpanded BM mesenchymal cells detected EDNRA expression in a subset of cells that coexpressed mesenchymal cell markers and had higher expression of proliferation genes. Immunohistochemistry revealed that the number of EDNRA+ cells in the interstitial BM increased as MM progressed; EDNRA+ cells were prevalent in areas near the MM focal growth. EDNRA+ cells were detached from CD34+ angiogenic cells and coexpressed RGS5 and periostin. Therefore, they likely originated from pericytes or SMCs. These findings identify a novel microenvironmental biomarker in MM and suggest that the presence of detached EDNRA+ cells indicates disrupted vasculature and increased angiogenesis. [ABSTRACT FROM AUTHOR]

Aim: Long non-coding RNAs (lncRNAs) play a significant role in the development of various diseases, including cancer, and have been investigated as potential diagnostic and prognostic markers. The specific mechanisms underlying their involvement in the progression and development of multiple myeloma (MM), as well as their potential as diagnostic markers, remain to be fully elucidated. This study aimed to elucidate the involvement of lncRNAs in the pathogenesis of MM, explore their relationship with clinical parameters, and assess their potential as biomarkers for MM diagnosis. Material and Methods: Patients above 18 years of age, diagnosed with MM and not yet receiving treatment, were included in the study. The expression levels of three lncRNAs (MALAT1, PANDAR, MEG3) regulated by the p53 gene were determined in a study involving 19 patients diagnosed with MM and 20 healthy volunteers. The expression levels were determined using RT-PCR. Results: The levels of plasma lncRNAs were observed to be significantly down-regulated (p<0.05) in the patient group. No significant difference was observed between disease stages and the expression levels of the lncRNAs. There was a negative correlation between lncRNA expression levels and albumin levels (p=0.019; p=0.048; p=0.033, respectively), while no significant associations were found with other clinicopathological characteristics. ROC analysis demonstrated that the plasma expression levels of lncRNAs had diagnostic value in predicting MM (AUC=0.729, p=0.015; AUC=0.742, p=0.010; AUC=0.703, p=0.031, respectively). Conclusion: In conclusion, MALAT1, PANDAR and MEG3 may serve as novel biomarkers for MM patients. Furthermore, these lncRNAs may be potential drug targets in MM. [ABSTRACT FROM AUTHOR]

Purpose: The role of Exosomal RNAs in the bone marrow microenvironment and their prognostic significance in multiple myeloma is not fully understood, especially in physically active populations such as athletes. This study aims to evaluate specific exosomal RNAs, including hsa-miR-124-3p, as potential prognostic markers for multiple myeloma in athletes. Experimental Design: Bone marrow fluid was collected from athletes diagnosed with multiple myeloma, showing varying treatment responses. Exosomes were isolated and characterized through dynamic light scattering, transmission electron microscopy, and Western blot analysis. The effect of these exosomes on PRMI8226 cell migration and proliferation was observed. MiRNA sequencing of the exosomes was performed, followed by bioinformatics analysis to identify differentially expressed miRNAs related to treatment outcomes. Clinical sample validation was conducted to ascertain the relevance of these findings in a broader athletic context. Results: The study revealed that bone marrowderived exosomes from athletes with multiple myeloma exhibit varied impacts on PRMI8226 cells based on the therapeutic response. Exosomes associated with poor prognosis were found to enhance PRMI8226 cell proliferation and migration. MiRNA sequencing identified distinct miRNA expressions in exosomes, with certain miRNAs enriched in cancer-related pathways. Notably, exosomal hsa-miR-124-3p was highly expressed in athletes exhibiting poor therapeutic responses. Conclusions: This study highlights the crucial role of exosomal miRNA in the progression and treatment of multiple myeloma in athletes. Specific miRNAs, such as hsa-miR-124-3p, hsa-miR-451b, and hsamiR- 509-3p, were predominantly expressed in athletes with less favorable treatment outcomes. Among these, hsa-miR-124-3p shows significant potential as a prognostic marker for therapeutic efficacy in athletes, providing a new avenue for early detection and management of multiple myeloma in this specific population. [ABSTRACT FROM AUTHOR]

Simple Summary: Myeloma, a blood cancer, is rare and hard to diagnose. People often suffer irreversible organ damage by the time of diagnosis. Myeloma is preceded by a premalignant phase that is easily identifiable on a blood test. Currently, there is no screening for this, because most people do not progress to myeloma. We aimed to inform guidelines and screening by refining our understanding of how patients developing myeloma describe their symptoms and how those symptoms relate to organ damage. We found that patients rarely describe 'bone pain' but simply 'pain'. Low-impact crush fractures of the backbones appear to be under-recognised as abnormal. At least 30% of patients have irreversible organ damage at diagnosis. People who developed myeloma fared better if they had previously been diagnosed to have the premalignant condition. Screening based on certain symptoms, possibly combined with imaging and laboratory results, may speed up the diagnosis of myeloma. Multiple myeloma (MM) patients risk diagnostic delays and irreversible organ damage. In those with newly diagnosed myeloma, we explored the presenting symptoms to identify early signals of MM and their relationships to organ damage. The symptoms were recorded in patients' own words at diagnosis and included diagnostic time intervals. Those seen by a haematologist >6 months prior to MM diagnosis were classified as precursor disease (PD). Most (962/977) patients provided data. Back pain (38%), other pain (31%) and systemic symptoms (28%) predominated. Patients rarely complain of 'bone pain', simply 'pain'. Vertebral fractures are under-recognised as pathological and are the predominant irreversible organ damage (27% of patients), impacting the performance status (PS) and associated with back pain (odds ratio (OR) 6.14 [CI 4.47–8.44]), bone disease (OR 3.71 [CI 1.88–7.32]) and age >65 years (OR 1.58 [CI 1.15–2.17]). Renal failure is less frequent and associated with gastrointestinal symptoms (OR 2.23 [CI1.28–3.91]), age >65 years (OR 2.14 [CI1.28–3.91]) and absence of back pain (OR 0.44 [CI 0.29–0.67]). Patients with known PD (n = 149) had fewer vertebral fractures (p = 0.001), fewer adverse features (p = 0.001), less decline in PS (p = 0.001) and a lower stage (p = 0.04) than 813 with de novo MM. Our data suggest subgroups suitable for trials of 'symptom-directed' screening: those with back pain, unexplained pain, a general decline in health or low-impact vertebral compression fractures. [ABSTRACT FROM AUTHOR]

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Simple Summary: Multiple myeloma has remained largely incurable despite improvements in patient outcomes in the era of targeted anti-myeloma agents. Targeted therapies used in oncology in recent years have significantly changed the way myeloma is treated and thus improved the prognosis for patients. We sought to identify new biomarkers for patient stratification and the prediction of treatment outcomes by applying targeted capture hybridization DNA sequencing (tchDNA-Seq) technology. We have evaluated plasma and bone marrow samples from a homogenous population of 23 patients, which IG rearrangements have the potential to provide important diagnostic, prognostic, and predictive information. We will likely be able to offer a more targeted and risk-adapted therapeutic approach to MM patients at different stages of their disease guided by these potential biomarkers. Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of pathogenic CD138+ plasma cells (PPCs) in bone marrow (BM). Recent years have seen a significant increase in the treatment options for MM; however, most patients who achieve complete the response ultimately relapse. The earlier detection of tumor-related clonal DNA would thus be very beneficial for patients with MM and would enable timely therapeutic interventions to improve outcomes. Liquid biopsy of "cell-free DNA" (cfDNA) as a minimally invasive approach might be more effective than BM aspiration not only for the diagnosis but also for the detection of early recurrence. Most studies thus far have addressed the comparative quantification of patient-specific biomarkers in cfDNA with PPCs and BM samples, which have shown good correlations. However, there are limitations to this approach, such as the difficulty in obtaining enough circulating free tumor DNA to achieve sufficient sensitivity for the assessment of minimal residual disease. Herein, we summarize current data on methodologies to characterize MM, and we present evidence that targeted capture hybridization DNA sequencing (tchDNA-Seq) can provide robust biomarkers in cfDNA, including immunoglobulin (IG) rearrangements. We also show that detection can be improved by prior purification of the cfDNA. Overall, liquid biopsies of cfDNA to monitor IG rearrangements have the potential to provide important diagnostic, prognostic, and predictive information in patients with MM. [ABSTRACT FROM AUTHOR]