Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model. DESIGN: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597). SETTING: Icelandic population of adults aged 40 years or older. PATIENTS: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample. MEASUREMENTS: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater. RESULTS: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds. LIMITATION: The prediction model will require external validation. CONCLUSION: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology. PRIMARY FUNDING SOURCE: International Myeloma Foundation and the European Research Council.

Real-World Registry on the Pharmacotherapy of Multiple Myeloma and Associated Renal and Pulmonary Impairments in the Greater Gulf Region: Protocol for a Retrospective Real-World Data Study.

BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking. OBJECTIVE: The primary objective of this study is to describe the disease characteristics and various treatment approaches or regimens used in the management of patients with RRMM in the Greater Gulf region. METHODS: We will conduct a regional, retrospective study collecting real-world and epidemiological data on patients with MM in countries of the Greater Gulf region. Medical records will be used to obtain the required data. Around 150 to 170 patients' records are planned to be retrospectively reviewed over 6 months without any cross-sectional or prospective intervention. Cases will be collected from Saudi Arabia, the United Arab Emirates, Kuwait, Oman, and Qatar. Descriptive as well as analytical statistics will be performed on the extracted data. The calculated sample size will allow us to estimate the percentages of RRMM cases with acceptable precision while complying with the challenges in light of data scarcity. We will obtain a comprehensive description of the demographic profile of patients with MM; treatment outcomes; the proportion of patients with MM with renal impairment and asthma, chronic obstructive pulmonary disease, or both at the time of diagnosis and any subsequent point; and data related to treatment lines, regimens, and MM-associated morbidities. RESULTS: Patient medical records were reviewed between June 2022 and January 2023 for eligibility and data extraction. A total of 148 patients were eligible for study inclusion, of whom 64.2% (n=95) were male and 35.8% (n=53) were female. The study is currently in its final stages of data analysis. The final manuscript is expected to be published in 2024. CONCLUSIONS: Although MM is a predominant hematological disease, data on its prevalence and patients' characteristics in the Greater Gulf region are scarce. Therefore, this study will give us real-world insights into disease characteristics and various management approaches of patients with MM in the Greater Gulf region. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49861.

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.

Real-world treatment patterns and outcomes for patients with multiple myeloma in Denmark, Finland and Sweden: An analysis using linked Nordic registries.

AIM: The Health outcomes and Understanding of MyelomA multi-National Study (HUMANS) was a large-scale, retrospective study conducted across Denmark, Finland and Sweden using linked data from national registries. We describe the characteristics, treatment patterns and clinical outcomes for patients with newly diagnosed multiple myeloma (NDMM) over 2010-2018. METHODS: Patients with NDMM who received MM-specific, first-line treatments, were categorised by treatment (autologous stem cell transplantation [ASCT] or a combination chemotherapy regimen based on bortezomib, lenalidomide or melphalan-prednisolone-thalidomide). RESULTS: 11,023 patients received treatment over 2010-2018. Time between diagnosis and treatment was shortest in Denmark (0.9 months), then Sweden (2.9 months) and Finland (4.6 months). Around one third of patients underwent ASCT. Lenalidomide-based regimens were prescribed to 23-28% of patients in Denmark and Finland, versus 12% in Sweden. Patients receiving lenalidomide had the longest wait for treatment, from 3.2 months (Denmark) to 12.1 months (Sweden). Treatment persistence was highest among patients receiving melphalan-prednisolone-thalidomide (7-8 months) in Finland and Sweden and lowest among those receiving bortezomib (3.5 months) in Finland. Overall survival (OS) was longest among patients with ASCT (7-10 years). Among patients receiving chemotherapy, OS (from diagnosis/treatment initiation), varied between cohorts. In a sensitivity analysis excluding patients with smouldering MM, OS decreased for all; for patients receiving bortezomib or lenalidomide, OS from diagnosis was 40-49 and 27-54 months, respectively. CONCLUSIONS: This population-based study of patients with NDMM receiving first-line MM-specific treatment, provides real-world data on treatment patterns and outcomes to complement data from randomised clinical trials.

Global, regional, and national burden and quality of care of multiple myeloma, 1990-2019.

Background: Multiple myeloma (MM) is the second most common haematologic malignancy, presenting a great disease burden on the general population; however, the quality of care of MM is overlooked. We therefore assessed gains and disparity in quality of care worldwide from 1990 to 2019 based on a novel summary indicator - the quality of care index (QCI) - and examined its potential for improvement. Methods: Using the Global Burden of Disease 2019 data set, we calculated the QCI of MM for 195 countries and territories. We used the principal component analysis to extract the first principal component of ratios with the combinations of mortality to incidence, prevalence to incidence, disability-adjusted life years to prevalence, and years of life lost to years lived with disability as QCI. We also conducted a series of descriptive and comparative analyses of QCI disparities with age, gender, period, geographies, and sociodemographic development, and compared the QCI among countries with similar socio-demographic index (SDI) through frontier analysis. Results: The age-standardised rates of MM were 1.92 (95% uncertainty interval (UI) = 1.68, 2.12) in incidence and 1.42 (95% UI = 1.24, 1.52) in deaths per 100 000 population in 2019, and were predicted to increase in the future. The global age-standardised QCI increased from 51.31 in 1990 to 64.28 in 2019. In 2019, New Zealand had the highest QCI at 99.29 and the Central African Republic had the lowest QCI at 10.74. The gender disparity of QCI was reduced over the years, with the largest being observed in the sub-Saharan region. Regarding age, QCI maintained a decreasing trend in patients aged >60 in SDI quintiles. Generally, QCI improved with the SDI increase. Results of frontier analysis suggested that there is a potential to improve the quality of care across all levels of development spectrum. Conclusions: Quality of care of MM improved during the past three decades, yet disparities in MM care remain across different countries, age groups, and genders. It is crucial to establish local objectives aimed at enhancing MM care and closing the gap in health care inequality.

Mode of progression in smoldering multiple myeloma: a study of 406 patients.

The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n = 71), 51 progressed by last follow-up; the MDEs included: bone lesions (37%), anemia (35%), hypercalcemia (8%), and renal failure (6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression (14%), bone pain (20%), and hospitalization/ED presentations due to MM complications/symptoms (4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

The Association of Agent Orange Exposure with the progression of monoclonal gammopathy of undetermined significance to multiple myeloma: a population-based study of Vietnam War Era Veterans.

Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, it is unclear whether TCDD/AO exposure (AO exposure hereafter) increases the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. We sought to evaluate the association in a nationwide study of US Veterans. A natural language processing algorithm was used to confirm MGUS and progression to MM. We included Veterans who were diagnosed with MGUS from 10/1/1999 to 12/31/2021 and served during the Vietnam War Era from 1/9/1962 to 5/7/1975. AO exposure was stratified according to three TCDD exposure levels: high (1/9/1962-11/30/1965), medium (12/1/1965-12/31/1970), or low (1/1/1971-5/7/1975). The association between AO exposure and progression was analyzed using multivariable Fine-Gray subdistribution hazard model with death as a competing event. The analytic cohort included 10,847 Veterans with MGUS, of whom 26.3% had AO exposure and 7.4% progressed to MM over a median follow-up of 5.2 years. In multivariable analysis, high exposure was associated with an increased progression rate (multivariable-adjusted hazard ratio 1.48; 95% confidence interval 1.02-2.16), compared to Veterans with no exposure. This information is critical to inform progression risk in patients diagnosed with MGUS and prior AO exposure. It is also applicable to MGUS patients with occupational TCDD exposure from herbicides and pesticides.

Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595.

Multiple myeloma incidence, mortality, and survival differences at the intersection of sex, age, and race/ethnicity: A comparison between Puerto Rico and the United States SEER population.

BACKGROUND: Multiple myeloma (MM) survival has increased during the last decades due to the introduction of new therapies. We investigated the intersectionality among age, sex, and race/ethnicity to better understand the pattern of MM incidence, mortality, and survival. METHODS: Puerto Rico (PR) Central Cancer Registry and the United States of America (US) Surveillance, Epidemiology, and End Results (SEER) Program databases were used. We analyzed MM incidence and mortality trends from 2001 to 2019 using Joinpoint regression models to calculate annual percent change (APC). Age-standardized rate ratios (SRR) for incidence and mortality were used to compare PR with US SEER racial/ethnic groups during 2015-2019. Five-year survival analyses were also performed stratified by age and sex. RESULTS: Regardless of age and race/ethnicity, males had higher MM incidence and mortality rates than females. PR had a higher increase in incidence rates of MM than other ethnic groups, regardless of sex and age (PR APC = 4.3 among males <65, 3.1 among males ≥65, 6.3 among females <65, and 2.6 among females ≥65 years old). No significant change in mortality APCs (p > 0.05) was observed in PR when stratified by age or sex while other groups showed a decrease. Among males < 65 years, PR had significantly higher incidence rates than non-Hispanic Whites (NHW), and US Hispanics (USH). However, among both males and females ≥ 65 years, PR had significantly lower MM mortality rates than NHW, non-Hispanic Blacks (NHB), USH, and US Overall. In terms of survival, PR showed the lowest 5-year overall survival among males < 65 years (54.6%, 95% CI: 47.2-61.5) and males ≥ 65 years (34.5%, 95% CI: 29.2-39.9) but not among females. CONCLUSION: The incidence of MM in PR increased significantly over the study period, particularly among younger women. Despite the introduction of new therapies, mortality rates in PR have remained stable while other ethnic groups show significant decreases among all intersections of sex and age.

Body size and risk of multiple myeloma in the Black Women's Health Study.

BACKGROUND: Obesity is an established risk factor for multiple myeloma (MM). Relatively few prior studies, however, have evaluated associations in Black populations. METHODS: Among 55,276 participants in the Black Women's Health Study, a prospective U.S. cohort established in 1995, we confirmed 292 incident diagnoses of MM over 26 years of follow-up. Multivariable Cox proportional hazard models, adjusted for age and putative MM risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of usual body mass index (BMI), BMI at age 18, height, and waist-to-hip ratio with MM. RESULTS: Compared to women with a usual adult BMI < 25 kg/m2, the HR associated with a usual adult BMI ≥ 35 kg/m2 was 1.38 (95% CI: 0.96, 1.98). For early adult BMI, the HR comparing women with BMI ≥ 25 vs. <25 kg/m2 was 1.57 (95% CI: 1.08, 2.28). Women who were heavy in both early and later life had the highest risk compared to those who were lean at both time points (HR: 1.60; 95% CI: 1.02, 2.52). Height was also associated with the risk of MM; the HR per 10 cm was 1.21 (95% CI: 1.02, 1.43). CONCLUSIONS: These results indicate that high early adult BMI is associated with a 57% increased risk of MM in Black women and potentially highlight the importance of weight control as a preventive measure.

Clinical characteristics, treatment patterns, and outcomes among African American and White patients with multiple myeloma in the United States.

Multiple myeloma (MM) is more common among Black/African American (AA) patients than White patients, but survival rate improvements are less pronounced for AA patients. This study evaluated treatment patterns and survival among 1810 AA and 5904 White adults in the United States with ≥1 MM treatment and ≥3 months of follow-up. Median time from diagnosis to systemic treatment was longer (37 [0-3053] vs. 35 [0-3664] days) and median time to stem cell transplant (SCT) was longer for AA than White patients (255 [1-2352] vs. 225 [1-3094] days), and AA patients were less likely to receive SCT (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.58-0.76). Despite disparities in treatment between AA and White patients, AA patients demonstrated lower risk of death (OR: 0.89; 95% CI: 0.81-0.96). These data highlight the value of equal access to care for the improvement of health outcomes in underserved populations.

Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups.

ABSTRACT: Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (White, 12% and Black, 25%). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (hazard ratio, 1.27; 95% confidence interval, 1.11-1.47; P < .001). This appeared to be driven by a marked difference in OS between White patients with and without DM but not in Black patients. In contrast, obesity was associated with better OS in Black patients but not in White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised nonobese diabetic (Rag1-/-/muscle creatinine kinase promoter expression of a human IGF1R [M] with a lysine [K] to arginine [R] point mutation) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with in controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phosphorylated S6 ribosomal protein (Ser235/236) levels, indicating greater activation of the mammalian target of rapamycin pathway. Our study is, to our knowledge, the first to evaluate racial differences in DM prevalence and survival in MM, as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients; and to improve survival in MM, DM management cannot be ignored.

Fracture rate after conventional external beam radiation therapy to the spine in multiple myeloma patients.

BACKGROUND CONTEXT: Conventional external beam radiation therapy (cEBRT) is used in multiple myeloma (MM) to treat severe pain, spinal cord compression, and disease-related bone disease. However, radiation may be associated with an increased risk of vertebral compression fractures (VCFs), which could substantially impair survival and quality of life. Additionally, the use of the Spinal Instability Neoplastic Score (SINS) in MM is debated in MM. PURPOSE: To determine the incidence of VCFs after cEBRT in patients with MM and to assess the applicability of the SINS score in the prediction of VCFs in MM. STUDY DESIGN: Retrospective multicenter cohort study. PATIENT SAMPLE: MM patients with spinal myeloma lesions who underwent cEBRT between January 2010 and December 2021. OUTCOME MEASURES: Frequency of new or progressed VCFs and subdistribution hazard ratios for potentially associated factors. METHODS: Patient and treatment characteristics were manually collected from the patients' electronic medical records. Computed tomography (CT) scans from before and up to 3 years after the start of radiation were used to score radiographic variables at baseline and at follow-up. Multivariable Fine and Gray competing risk analyses were performed to evaluate the diagnostic value of the SINS score to predict the postradiation VCF rate. RESULTS: A total of 127 patients with 427 eligible radiated vertebrae were included in this study. The mean age at radiation was 64 years, and 66.1% of them were male. At the start of radiation, 57 patients (44.9%) had at least one VCF. There were 89 preexisting VCFs (18.4% of 483 vertebrae). Overall, 39 of 127 patients (30.7%) reported new fractures (number of vertebrae (n)=12) or showed progression of existing fractures (n=36). This number represented 11.2% of all radiated vertebrae. Five of the 39 (12.8%) patients with new or worsened VCFs received an unplanned secondary treatment (augmentation [n=2] or open surgery [n=3]) within 3 years. Both the total SINS score (SHR 1.77; 95% confidence interval (CI) 1.54-2.03; p<.001) and categorical SINS score (SHR 10.83; 95% CI 4.20-27.94; p<.001) showed an independent association with higher rates of new or progressed VCFs in adjusted analyses. The use of bisphosphonates was independently associated with a lower rate of new or progressed VCFs (SHR 0.47 [95% CI 0.24-0.92; p=.027]). CONCLUSIONS: This study demonstrated that new or progressed VCFs occurred in 30.7% of patients within 3 years, in a total of 11.2% of vertebrae. The SINS score was found to be independently associated with the development or progression of VCFs and could thus be applied in MM for fracture prediction and possibly prevention.

Real-world treatment patterns in patients initiating third-line therapy for relapsed or refractory multiple myeloma in Germany, Italy, the United Kingdom, France, and Spain.

OBJECTIVES: To retrospectively analyze real-world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third-line treatment in Europe. METHODS: German and Italian administrative claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016-2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms. RESULTS: Across all countries, immunomodulatory imide drug (IMiD)-based regimens were prominent in the third-line setting. From 2016 to 2020, lenalidomide-dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib-lenalidomide-dexamethasone (67.5%) in the UK, pomalidomide-dexamethasone (17.1%) in France, and daratumumab-bortezomib-dexamethasone (15.0%) in Spain. In the historical data (2016-2018), third-line lenalidomide- and pomalidomide-dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti-CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%). CONCLUSIONS: From 2016 to 2021, third-line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice.

Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma.

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

Addressing the disparities: the approach to the African American patient with multiple myeloma.

There are significant disparities with regards to incidence, timely diagnosis, access to treatment, clinical trial participation and health care utilization that negatively impact outcomes for African American patients with multiple myeloma. Health care providers have a role in ameliorating these disparities with thoughtful consideration of historical, sociocultural, individual and disease characteristics that influence the care provided to African American patient population. This review by a group of experts committed to health disparity in multiple myeloma provides a snapshot of disparities at both biologic and non-biologic levels, barriers to clinical care, and best practices to ensure that African American patients receive the best care available.

Approaches to developing de novo cancer population models to examine questions about cancer and race in bladder, gastric, and endometrial cancer and multiple myeloma: the Cancer Intervention and Surveillance Modeling Network incubator program.

BACKGROUND: We are developing 10 de novo population-level mathematical models in 4 malignancies (multiple myeloma and bladder, gastric, and uterine cancers). Each of these sites has documented disparities in outcome that are believed to be downstream effects of systemic racism. METHODS: Ten models are being independently developed as part of the Cancer Intervention and Surveillance Modeling Network incubator program. These models simulate trends in cancer incidence, early diagnosis, treatment, and mortality for the general population and are stratified by racial subgroup. Model inputs are based on large population datasets, clinical trials, and observational studies. Some core parameters are shared, and other parameters are model specific. All models are microsimulation models that use self-reported race to stratify model inputs. They can simulate the distribution of relevant risk factors (eg, smoking, obesity) and insurance status (for multiple myeloma and uterine cancer) in US birth cohorts and population. DISCUSSION: The models aim to refine approaches in prevention, detection, and management of 4 cancers given uncertainties and constraints. They will help explore whether the observed racial disparities are explainable by inequities, assess the effects of existing and potential cancer prevention and control policies on health equity and disparities, and identify policies that balance efficiency and fairness in decreasing cancer mortality.

A population-based study on incidence trends of myeloma in the United States over 2000-2020.

Myeloma is one of the most common types of haematological malignancies. We aimed to investigate the incidence rates of myeloma by sex, race, age, and histological subgroups in the United States (US) over 2000-2020. Data were retrieved from the the Surveillance, Epidemiology, and End Results (SEER) 22 database. The International Classification of Diseases for Oncology version 3 morphological codes 9731, 9732, and 9734 were assigned for solitary plasmacytoma of bone, plasma cell myeloma, and extraosseous plasmacytoma, respectively. Average annual percent change (AAPC) and the pairwise comparison with the parallelism and coincidence were reported. All estimates were reported as counts and age-adjusted incidence rates per 100,000 individuals. Over 2000-2019, most of myeloma cases were among those aged at least 55 years (85.51%), men (54.82%), and non-Hispanic Whites (66.67%). Among different subtypes, plasma cell myeloma with 193,530 cases had the highest frequency over the same period. Also, there was a significant decrease in the age-standardized incidence rate of myeloma across all races/ethnicities in both sexes within all age groups (AAPC: - 8.02; 95% confidence interval (CI): - 10.43 to - 5.61) and those aged < 55 (AAPC: - 8.64; 95% CI - 11.02 to - 6.25) from 2019 to November 2020. The overall trends of myeloma incidence rates were not parallel, nor identical. There was an increase in myeloma incidence in both sexes, with a highly increasing rate, particularly among younger Hispanic and non-Hispanic Black women over 2000-2019. However, a remarkable decline was observed in the incidence rates following the COVID-19 pandemic in 2020.