Screening For Multiple Myeloma Research Articles

Multiple myeloma incidence and mortality trends in the United States, 1999–2020

Multiple myeloma (MM) is a plasma cell disorder accounting for approximately 10% of hematologic malignancies. There is limited epidemiological evidence regarding the long-term trends and disparities in MM in the US. We conducted a multiple time point cross-sectional study using MM incidence rate data from the Surveillance, Epidemiology, and End Results (SEER) database and mortality data from the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause of Death database between 1999 and 2020. During this period, MM incidence has steadily increased, while MM mortality has steadily decreased, with substantial racial and ethnic disparities. Non-Hispanic Black individuals exhibited the highest incidence rates, which consistently rose from 12.02 (95% CI 10.54, 13.64) in 1999 to 14.20 (95% CI 12.93, 15.55) per 100,000 population by 2020. Non-Hispanic American Indian/Native Alaskans and Asian/Pacific Islanders demonstrated the lowest incidence rates of 5.59 (95% CI 2.69, 10.04) and 3.56 (95% CI 2.94, 4.27) per 100,000 population in 1999 to 5.76 (95% CI 3.49, 8.90) and 3.92 (95% CI 3.46, 4.42) per 100,000 population, respectively, by 2020. Disparities by gender, age, US census region, and rurality were observed, underscoring the importance of targeted, equity-centered interventions and MM screening initiatives for at-risk populations.

The casual relationship between autoimmune diseases and multiple myeloma: a Mendelian randomization study

Observational studies showed possible associations between systemic lupus erythematosus and multiple myeloma. However, whether there is a casual relationship between different types of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis, and juvenile idiopathic arthritis) and multiple myeloma (MM) is not well known. We performed a two-sample Mendelian randomization (MR) study to estimate the casual relationship. Summary-level data of autoimmune diseases were gained from published genome-wide association studies while data of MM was obtained from UKBiobank. The Inverse-Variance Weighted (IVW) method was used as the primary analysis method to interpret the study results, with MR-Egger and weighted median as complementary methods of analysis. There is causal relationship between primary sclerosing cholangitis [OR = 1.00015, 95% CI 1.000048–1.000254, P = 0.004] and MM. Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MM. Considering the important role of age at recruitment and body mass index (BMI) in MM, we excluded these relevant instrument variables, and similar results were obtained. The accuracy and robustness of these findings were confirmed by sensitivity tests. Overall, MR analysis suggests that genetic liability to primary sclerosing cholangitis could be causally related to the increasing risk of MM. This finding may serve as a guide for clinical attention to patients with autoimmune diseases and their early screening for MM.

Quantitative risk factor analysis of prior disease condition and socioeconomic status with the multiple myeloma development: nationwide cohort study

Early diagnosis and following management are important determinants of the prognosis of multiple myeloma (MM). However, screening for MM is not routinely performed because it is rare disease. In this study, we evaluated the association of prior disease condition and socioeconomic status (SES) with MM diagnosis and developed a simple predictive model that can identify patients at high risk of developing MM who may need screening using nationwide database from South Korea. According to multivariate logistic regression analysis, eight prior disease conditions and SES before diagnosis were shown to be predictors of MM development and selected for score development. Total prediction scores were categorized into four groups: patients without any risk (≤ 0) intermediate-1 (0.5–9), intermediate-2 (9–14), and high risk (> 14). The odds ratios for developing MM in the intermediate-1, intermediate-2, and high-risk groups were 1.29, 3.07, and 4.62, respectively. The association of prior disease conditions and SES with MM diagnosis were demonstrated and the simple scoring system to predict the MM risk was developed. This scoring system is also provided by web-based application and could be a useful tool to support clinicians in identifying potential candidates for MM screening.

Update on the outcome of M-protein screening program of multiple myeloma in China: A 7-year cohort study.

To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9 months, p < 0.001, HR: 2.12, 95% CIs: 1.69-2.65), with median follow-ups of 32.6 and 27.4 months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3 months, p < 0.001, HR: 2.49, 95% CIs: 1.81-3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screening-driven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes.

Abstract C115: Framework for a community-based multiple myeloma screening program

Abstract Purpose: We develop a framework for a community-based screening program for multiple myeloma (MM). MM is known to be twice as common in Black/African American (B/AA) persons compared to white persons and B/AA patients have a higher risk of delay in initial treatment compared to white patients. Therefore, we developed a community-wide screening program for B/AA persons 50 years and older. As the first of these programs, we reveal an organizational framework that prioritizes engagement with key community partners who address barriers to cancer screening. Experimental Procedures: We expand organizational development knowledge about how to implement community-based MM screening and address barriers. The study uses an iterative and qualitative continuous improvement process. The study draws on literature review and multi-disciplinary team collaboration among clinicians, researchers, administrators, and the Cleveland Clinic Community Outreach Program (Cleveland Outreach). Data Summary: Our framework includes three interrelated partners and each address barriers to MM screening: 1) Cleveland Clinic Cancer Center. The multi-disciplinary team designs an educational brochure, secures pilot grant funding, plans for insurance/financial assistance as needed, develops care algorithms, and evaluates the impact of the program. Cleveland Outreach, a department within the Cancer Center, uses the Harold Freeman model as its foundational approach, which includes patient navigators and community outreach managers who are culturally/linguistically matched to medically underserved communities. The Cancer Center addresses barriers including program implementation despite a lack of national screening guidelines, insurance/financial barriers, and patient navigation to address fears and health literacy. 2) Faith-based organizations. Church leaders committed to cancer prevention participate in Cleveland Outreach’s faith-based outreach model. Faith-based partners address barriers of trust and fear. Also, by providing space at churches for on-site screening blood draws, they address transportation barriers. 3) Clinicians at Federally Qualified Health Centers (FQHC’s). Providers and nurses at FQHC’s receive a Continuing Medical Education program about MM screening designed/funded by the Cancer Center. From within the community, providers notify medically underserved patients about the screening. With their primary care patient population, FQHC partners address barriers such as trust, health literacy, and fear of blood draws. They facilitate on-site screening at FQHC’s and health fairs, which addresses transportation barriers. Conclusions: Given that there are no universal guidelines for MM screening, we develop a novel approach to early disease detection in B/AA patients. Our framework is a partnership between the Cancer Center, faith-based organizations, and FQHC’s. Collaboratively, we address barriers to screening including fear, trust, insurance/financial, health literacy, transportation, and patient navigation if abnormal results suggest the need for further testing. Citation Format: Heather McKee Hurwitz, Kimberly Bell, Diana Basali, Raymond D. Jackson II, Jason Valent. Framework for a community-based multiple myeloma screening program [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C115.

Update on the Outcome of M-Protein Screening Program of Multiple Myeloma in China: A 7-Year Cohort Study

Background: To improve the early detection rate of multiple myeloma(MM), the M-protein screening system has been performed in hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based screening integrated into routine blood tests. This study updated the 7-year follow-up findings of MM patients diagnosed by screening-driven and end-organ symptom-driven pattern. Methods: The retrospective study compared the characteristics and results of two alternative diagnosis patterns by reviewing the plasma cell disease database of MM patients diagnosed between January 2014 and October 2021 at hospital. Screening-driven patients were classified as having an incidental finding of M-protein during workup of unrelated medical conditions or routine body check-up, while symptom-driven patients exhibited myeloma-related end-organ damage's symptoms. Results: Over 300 million serum protein electrophoresis tests were performed during 7 years, with 1-2 percent yielding positive results, prompting patients to seek further examination. Of 911 confirmed MM cases (concurrent amyloidosis excluded), 366 were assigned to the screening-driven group while 545 were to the symptom-driven group. In comparison to the symptom-driven group, the screening group had more IgG phenotypes (P=0.001), earlier ISS stages(P<0.001), fewer disease-related symptoms (hypercalcemia, renal insufficiency, anemia and bone lesion), lower ECOG scores (P<0.001), less extramedullary disease (P<0.001), a lower rate of bone marrow plasma cells(P<0.001), and lower level of lactate dehydrogenase(LDH)(P=0.018) at baseline. Regarding first-line therapy, it was found that while both groups had comparable exposure to proteasome inhibitor and immunomodulatory drugs as well as rates of the best efficacy, the screening group was more likely to have >2-drug regimens and ≧ 6 induction cycles than the other group. Patients detected through screening had a significantly longer median progression-free survival (PFS) time than the symptom-driven group (62.2 VS 24.9 months) with median follow-ups of 32.9 and 27.8 months, respectively. Furthermore, the screening group did not achieve the median overall survival (OS) time, which was 62.3 months in the symptom group. In multivariate cox analysis, the screening-driven diagnostic pattern remains an independent prognostic factor indicating favorable PFS and OS in MM patients after adjusting for well-acknowledge myeloma prognostic factors. Conclusion: Routine M-protein screening for MM in hospital patients results in an earlier diagnosis and better patient outcomes in China. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

MGluR5 promotes the progression of multiple myeloma in vitro via Ras-MAPK signaling pathway.

Multiple myeloma (MM) is a malignant plasma cancer which remains difficult to be cured. Recently, numerous research studies have appeared, exploring MM from molecular level. However, there is no study about the impact of metabotropic glutamate receptors (mGluRs), especially mGluR5, on MM progression. Thus, the present research was dedicated to the exploration of the influence of mGluR5 on MM. In this research, we used quantitative real-time polymerase chain reaction (qRT-PCR) to check the gene expression in MM, western blot assay to check the protein expression of the gene, MTT assay to quantify the cell viability, and flow cytometry (FCM) apoptosis method to evaluate cell apoptosis in order to acquire the results. The purpose was to assess the role of mGluR5 in MM cells. The qRT-PCR was used and it was found that mGluR5 was overexpressed in MM cell lines and MM tissues compared to normal ones. To better observe the function of mGluR5 in MM, cell viability and apoptosis were checked using MTT and FCM apoptosis assays after the treatment with agonists and antagonists. Agonist-induced mGluR5 upregulation could promote MM cell viability and inhibit apoptosis. The same results were obtained through MTT and FCM apoptosis assays after upregulation and downregulation of mGluR5 by transfection. To further investigate the inner mechanism, the effect of mGluR5 on Ras-MAPK pathway was checked using western blot. It was found that the upregulation of mGluR5 could activate the Ras-MAPK pathway. The mGluR5 might be involved in promoting cell proliferation and inhibiting cell apoptosis in MM. It can be an essential biomarker in the screening for MM and a potential part of future MM therapies.

Optimization of workflow and screening panels for the detection of malignant monoclonal gammopathies.

Multiple myeloma (MM) is one of the hematologic malignancies with a greater delay in diagnosis. Laboratories receive numerous MM screening test requests without a specific suspicion, which entails a substantial workload and reduces the efficiency of laboratories. Objective: to increase the efficacy of MM screening protocols. The results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein immunofixation electrophoresis, and serum free light chain assays of 75 patients with MM, three with amyloidosis, and a patient with solitary plasmocytoma were collected. The frequency of a set of biochemical alterations in these patients was compared with that in controls (n=120). A validation of the screening algorithm was carried out in 261 consecutive patients with a clinical or analytical suspicion of MM. SPEP+SFLC or SIFE+SFLC (98% sensitivity) were the screening algorithms with the highest sensitivity. Prospectively, the SPEP+SFLC detected 27 of the 28 confirmed cases of MG and saved 15h of work. Alterations in five of the six parameters studied were more frequent in the study group, with a cumulative value of≥3 parameters altered (61.1 vs. 1.7%) (positive predictive value: 85%; negative predictive value: 94%). The SPEP+SFLC screening protocol demonstrated the highest sensitivity and was the least time-consuming protocol. In addition, this protocol improves diagnostic sensitivity and laboratory performance.

Multiple myeloma detection based on blood plasma surface-enhanced Raman spectroscopy using a portable Raman spectrometer

The feasibility of surface enhanced Raman spectroscopy (SERS) for multiple myeloma (MM) detection is investigated in this work. SERS measurements of silver nanoparticle mixed blood plasma samples are performed using a low-cost and portable Raman spectrometer. The tentative assignment of Raman peaks indicates an increase in amino acids, nucleic acid base content and a decrease in cholesterol ester in the MM group. Combined with the multivariate analysis method of principle component analysis (PCA) and linear discriminate analysis (LDA), a diagnosis result for 32 samples with a sensitivity of 93.75% and specificity of 87.5% is achieved. The performance of the corresponding receiver operating characteristic (ROC) curve is 0.957. It is a potential rapid and non-invasive method for preliminary MM screening.

The Immunotyping Distribution of Serum Monoclonal Paraprotein and Environmental Impact on Multiple Myeloma (MM) and Monoclonal Gammopathy of Uncertain Significance (MGUS) in Taiwan: A Medical Center-Based Experience.

Whether ambient exposure to environmental pollutants leads to hematopoietic malignancies such as multiple myeloma (MM) remains to be ascertained. Therefore, we aimed to investigate the immunotyping distribution of serum monoclonal paraprotein and the environmental influence on MM and monoclonal gammopathy of uncertain significance (MGUS) in the Taiwanese population. Serum protein electrophoresis with immunosubtraction by the capillary zone electrophoresis method was performed as primary screening for MM and MGUS. Clinical, pathological, and residence data of patients were also obtained. From August, 2013 to June, 2015, a total of 327 patients underwent serum protein electrophoresis with immunosubtraction. Among these, 281 demonstrated no remarkable findings or non-malignant oligoclonal gammopathy, 23 were detected to have MGUS, 18 were identified as MM, and a further 5 were found as other malignancies. The most frequent immunotyping distribution of serum monoclonal paraprotein was IgG kappa (54.3%, n=25), followed by IgA lambda (15.2%, n=7) and IgG lambda (10.9%, n=5) in subjects with gammopathy. Additionally, it was shown that the elderly (OR: 4.61, 95% CI: 1.88-11.30, P<0.01) and males (OR: 2.04, 95% CI: 1.04-4.02, P=0.04) had significantly higher risk of developing MM and MGUS. There was no obvious impact of environmental factors on the health risk of MM and MGUS evolution (OR: 0.77, 95% CI: 0.40-1.50, P=0.49). The most frequent immunotyping distribution of serum monoclonal paraprotein included IgG kappa, IgA lambda and IgG lambda in MM and MGUS in the Taiwanese population. The elderly and male subjects are at significantly higher risk of MM and MGUS development, but there was no obvious impact of environmental factors on risk.

Establishment and Validation of Serum Free Light Chain Reference Intervals in an Ethnic Chinese Population

Quantification of serum free light chains (FLC) and calculation of a kappa/lambda ratio using polyclonal antisera based immunoassays provide laboratories with a sensitive alternative to urine protein electrophoresis (UPE). However, the published 0.26 - 1.65 serum FLC kappa/lambda ratio reference intervals may not be suitable for different ethnic populations (such as the Han Chinese population presented) and require validation. This is particularly important where there are significant differences in ethnicity, and hence HLA prevalence, in the population studied. Serum FLC reference intervals were determined using 326 Han Chinese blood donor volunteers. Sensitivities and specificities for the (i) serum FLC kappa/lambda ratio reference interval and (ii) UPE analyses were determined using 68 pre-treatment, serum immunofixation (sIFE) positive multiple myeloma (MM) patient samples, 54 sera from MM patients undergoing treatment, and 56 sIFE-negative samples from patients with no plasma cell dyscrasia (PCD). The 100% range for the serum FLC kappa/lambda ratio in this Han Chinese population was 0.32 - 1.52. Both Han Chinese blood donors and published kappa/lambda ratio reference ranges demonstrated higher diagnostic sensitivity and specificity for PCD than was seen with UPE. Highly abnormal serum FLC kappa/lambda ratios were observed in 68% of MM patients who had a negative UPE. Furthermore, a MM screening panel of SPE plus serum FLC assays achieved 100% diagnostic sensitivity compared to 97% for a UPE plus SPE algorithm. For MM patients undergoing therapy, 70% of UPE negative samples displayed an abnormal FLC ratio. This study confirms the requirement to verify normal FLC reference ranges in local populations. This Han Chinese reference range is narrower than the published range. FLC testing provides a robust, sensitive, and specific alternative to classic UPE assessment.

A Biomathematical Modeling Approach to Central Nervous System Radioligand Discovery and Development

The development of a successful PET or SPECT molecular imaging probe is a complex, time-consuming, and expensive process that suffers from high attrition. To address this problem, we have developed a biomathematical modeling approach that aims to predict the in vivo performance of radioligands directly from in silico/in vitro data. The method estimates the in vivo nondisplaceable and total uptake of a ligand in a target tissue using a standard input function and a 1-tissue-compartment model with a parsimonious parameter set (influx rate constant K(1), efflux rate constant k(2), and binding potential BP(ND)) whose values are predicted from in silico/in vitro data including lipophilicity, molecular volume, free fraction in plasma and tissue, target density, affinity, perfusion, capillary surface area, and apparent aqueous volume in plasma and tissue. The coefficient of variation of the BP(ND) (%COV[BP(ND)]) metric, derived from Monte Carlo simulations, is used to estimate the in vivo performance of candidate compounds. A total of 28 compounds for 10 targets was evaluated using our method to predict their in vivo performance and validated against measured in vivo PET data in the Yorkshire/Danish Landrace pig. The predicted K(1), k(2), and BP(ND) values were generally consistent with the values estimated from in vivo PET data. The model resulted in small %COV[BP(ND)] values for widely accepted good ligands such as (11)C-flumazenil (2.02%) and (11)C-raclopride (2.55%), whereas higher values resulted from poor ligands such as (11)C-(R)-PK11195 (13.34%). Of 4 candidates for the GlyT1 transporter, the model selected (11)C-GSK931145 (2.11%) as the most promising ligand, which was consistent with historical decisions made on the in vivo PET data. A biomathematical modeling approach has the potential to predict the in vivo performance of ligands from in silico/in vitro data and aid in the development of molecular imaging probes.

Familial multiple myeloma: report on two families and discussion of screening options.

Multiple myeloma (MM) is a relatively rare haematological malignancy seen in older persons. It has an unknown aetiology and usually occurs incidentally within a family. However, several families have been reported with multiple cases of MM, so that the existence of hereditary MM has been postulated although no causative germline mutations have been detected so far. First-degree relatives of MM patients have been reported to have a relative risk between two and four times higher than normal of developing MM and we presume the risks are higher for relatives in the case of familial MM. Here we report on two families with MM who requested presymptomatic screening of healthy relatives. Although risk estimates for asymptomatic relatives in these types of families are not available, a clinically significant risk of developing MM cannot be excluded. We suggest that, in a research setting, screening for MM could be offered to individuals with more than one first-degree affected relative, or to those with one first-degree and at least one second-degree relative with MM. We propose a screening programme of annual protein electrophoresis of blood and urine, starting at age 40 (or earlier if a family member presented with MM at a younger age).