bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of overall survival (OS) of elderly patients with multiple myeloma: A National Cancer Database (NCDB) analysis of years 2004-2017.
Authors: Chaulagain Chakra Pani , Saba Ludovic , Liang Hong , Dominguez Barbara , Fu Chieh Lin 
Published: June 2023

e20035 Background: The survival of older adults with multiple myeloma (MM) continues to improve due to advancements in therapy but there is limited real-world data around the outcome of elderly (≥ 75 years old) MM patients. These patients are at risk due to comorbidities, frailty and potential for reduced tolerance to treatment. In this IRB approved retrospective analysis, the NCDB was used to evaluate the 30-day mortality and the determinants of overall survival (OS) of elderly MM patients who were treated at commission on cancer (CoC) accredited facilities across the USA. Methods: Using the NCDB, we identified N = 54,766 patients ≥ 75 years old diagnosed and treated for MM from 2004 to 2017. Multivariable cox regression analysis with backward elimination was utilized to identify the independent survival factors, using significance level of p < 0.05. Kaplan-Meier survival curves were produced, and SAS version 9.4 was used to analyze the data. Results: Overall median survival time was 23 months; while survival rates of 1, 3, and 5-year were 61.9%, 38.0%, and 23.6%, respectively. Multivariable cox regression analysis with backward elimination method revealed that there were 10 significant independent survival factors including age, sex, race, ethnicity, education level, Charlson-Deyo score, facility type, median income, year of diagnosis, and treatment-regimen. Male patients were more likely to die compared to female patients (HR = 1.08, p < 0.0001). Black patients were predicted to have less death events compared to White patients (HR = 0.90, p < 0.0001). In addition to that, patients of Hispanic ethnicity were more likely to die compared to non-Hispanic patients (HR = 1.16, p < 0.0001). Subjects who were treated in non-academic facilities were more likely to suffer death compared to the ones who received care in academic centers (HR = 1.15, p < 0.0001). Patients with median income < $38,000 (HR = 1.10, p < 0.0001), $38,000-$47,999 (HR = 1.06, p = 0.0011) and $48,000-$62,999 (HR = 1.04, p = 0.0031) were more likely to die compared to patients with higher median income ≥ $63,000. The hematopoietic stem cell transplantation utilization rate was 0.1%. The 30-day mortality rate was 8%. Detailed analysis will be presented. Conclusions: This large real-world analysis of elderly MM patients shows that White and Hispanic patients have inferior OS compared to Blacks and non-Hispanics. Patients with lower economic status and those treated at a non-academic facility also had inferior survival compared to those with higher income and with access to care at an academic facility. The 30-day mortality is strikingly high (8%) in the elderly. The unacceptably high mortality could be improved by facilitating access to high quality care and prompt use of novel agents. Prospective studies are needed to identify and address determinants of disparity in MM care in elderly patients.
Socioeconomic factors associated with a late-stage multiple myeloma diagnosis: An analysis of the National Cancer Database.
Authors: Patel Chirag , Townley Liam P. , Silberstein Peter T. , Gallegos Jillian Marie 
Published: June 2023

e20036 Background: Multiple myeloma is an aggressive monoclonal plasma cell proliferative disorder that is the second most common hematologic malignancy. On a global scale, multiple myeloma led to an estimated 106,000 deaths in 2018 alone. The exact cause of multiple myeloma is not well understood. Later stage of diagnosis is correlated with worse outcomes; thus, it is critical to assess the socioeconomic factors associated with diagnosis at early versus late stages. Methods: Using the National Cancer Database, we aimed to identify associations between socioeconomic factors of patients that present with Revised International Staging System (R-ISS) stage I multiple myeloma in comparison to R-ISS stage III at diagnosis. In this study, 5,512 patients from the National Cancer Database who were diagnosed with R-ISS stage I and stage III multiple myeloma were analyzed based on age, ethnicity, race, education, insurance type, income, education, geographic location, facility type, sex, Charlson-Deyo score, and urban or rural setting. Demographic factors of patients that presented with stage I and stage III disease were analyzed using chi square, ANOVA, and multivariate analyses. All patients included in the study were diagnosed with multiple myeloma between 2004 and 2020. Results: We identified significant (P < 0.05) associations between insurance type, median income, education, rural setting, and Charlson-Deyo score with diagnosis of R-ISS stage III multiple myeloma. For insurance type, private insurance, other government insurance, and Medicaid had lower percentages of R-ISS stage III diagnosis than patients without insurance (P < 0.001). Medicaid and over government insurance were up to 70% less likely to present with stage III MM than patients without insurance (P < 0.001). Regarding income and education, patients from a zip-code associated with an income of < $38,000 and zip-codes with lower levels of high school diploma had higher rates of stage III multiple myeloma diagnosis (P < 0.001). Patients from completely rural or less than 2,500 urban population adjacent to a metro area (P < 0.005) and not adjacent to a metro area (P < 0.025) showed significant increase in later stage multiple myeloma diagnosis than those from a metro setting with population above one million. Patients with Stage III at presentation were older than patients with stage I on average (P < 0.001). There were no significant differences seen based on race, sex, ethnicity, or region in the United States. Conclusions: Factors associated with increased likelihood of later stages of diagnosis of multiple myeloma include insurance type, median income, education, and rural location. Future analysis should further investigate the specific barriers to early patient diagnosis and treatment due to insurance type, education level, and rural setting.
Clinical validation of next-generation sequencing-based clonality assays for minimal residual disease tracking in multiple myeloma.
Authors: Lin Chuanming , Jian Qijie , Huang Zoufang , Xie Shuiling , Xin Liuyan , Wu Haiyan , Pang Fei , Liao Changfeng , Chen Yijian 
Published: June 2023

e20037 Background: The prognosis of multiple myeloma (MM) patients is dependent on minimal residual disease (MRD) status after treatment. Multicolor flow cytometry (MFC) as a clinical MRD evaluation method has certain limitations regarding sample requirement, sensitivity and specificity. Next-generation sequencing (NGS)-based B cell receptor (BCR) clonality assessment has an edge in lymphoid clone MRD detection, with easier sample preparation and higher sensitivity. NGS-based BCR clonality assays were performed to evaluate curative effect and track MRD of MM patients, and its performance in testing samples with limited DNA contents was explored. Methods: In this retrospective study, newly diagnosed or relapsed MM patients with paired sample collected before and after initial treatment were included, and OriMIRACLE L NGS assay were used for BCR clonality detection in genomic DNA (gDNA) extracted from clinical residual marrow smear samples. The quantitative accuracy of NGS was compared to MFC. The concordance of MRD between MFC, NGS and clinical response assessment were analyzed. Results: From December 2016 to April 2022, 29 patients were included with a median age of 65 years old. The gDNA input of the sample collected before treatment was 100.0 ng, and the median DNA content of the sample collected after treatment was 1673.4 ±594.8 ng. The quantitative results of NGS and MFC were consistent in samples with a frequency of cancer cells of above 1x10-4 among all nucleated cells. BCR clonality detection in 23 newly diagnosed and 6 relapsed cases showed a 100% sensitivity at diagnosis. For post-treatment monitoring, patients with positive MRD by both MFC and NGS (n = 18), the MRD results were consistent with clinical response assessment. One of the patients achieved complete response (CR), while the remaining patients were unable to achieved CR. The CR patient was relapsed after 134 days. The clinical responses of 11 cases with negative MRD by MFC and positive MRD by NGS were reviewed. There were 7 cases with CR, 3 cases with very good partial response or partial response, and one case with stable disease. Among those CR patients, except for one patient who was lost to follow-up, 4 patients who underwent continuous treatment were still CR and 2 patients who had treatment discontinued recurred at 67 and 134 days. Conclusions: OriMIRACLE L NGS assay showed the higher sensitivity and specificity of MRD evaluation than MFC. For patients with negative MRD by MFS and positive MRD by NGS, recurrence might occur in case of treatment discontinuation. It is recommended to consider carefully that whether maintenance treatment is required in such cases.
A matching-adjusted indirect treatment comparison of elranatamab in patients with triple-class exposed relapsed/refractory multiple myeloma: Comparisons with belantamab mafodotin, selinexor plus dexamethasone, and real-world physician’s choice of treatment.
Authors: Hlavacek Patrick , Mol Isha , Hu Yannan , Cappelleri Joseph C. , Chu Haitao , Aydin Didem 
Published: June 2023

e20038 Background: Elranatamab, a bispecific antibody targeting B-cell maturation antigen on multiple myeloma (MM) cells and CD3 on T cells, is being evaluated as a monotherapy in the MagnetisMM-3 trial (MM3; NCT04649359) in patients with triple-class exposed (TCE) relapsed/refractory MM. While there is no standard of care for TCE MM, belantamab mafodotin (belamaf) and selinexor plus dexamethasone (sel-dex) are treatment options. LocoMMotion is a prospective, non-interventional study investigating real-world physician’s choice of treatment (PCT) in patients with TCE MM. In the absence of head-to-head trials, unanchored matching-adjusted indirect comparisons (MAIC) were conducted to compare the relative efficacy across comparators. Methods: Individual patient-level data were obtained for elranatamab from MM-3 (data cut Oct 2022). Aggregated data for belamaf, sel-dex, and PCT were obtained from DREAMM-2 (NCT03525678), STORM (NCT02336815), and LocoMMotion (NCT04035226). Unanchored MAICs were conducted to compare the relative treatment effect on objective response rate (ORR) accounting for potential different distributions of prognostic variables (PVs) and effect modifiers (EMs). In the base case, PVs identified via logistic regressions based on MM-3 data were adjusted. In sensitivity analyses, PVs/EMs identified from the literature were added. Relative treatment effects were measured by rate differences and odds ratios. Results: After MAIC adjustments, the selected PVs/EMs were balanced in each comparison. The table presents the results from the naïve comparison with no MAIC adjustment plus the MAIC base case. The ORR of elranatamab was statistically higher than belamaf, sel-dex, and PCT in LocoMMotion. Results were consistent across all sensitivity analyses. Conclusions: Elranatamab had a significantly higher ORR than belamaf, sel-dex, and real-world PCT in LocoMMotion for patients with TCE MM, demonstrating its clear clinical benefit for this population. [Table: see text]
The efficacy of autologous hematopoietic cell transplantation in standard risk multiple myeloma refractory to multiple therapies.
Authors: Awada Hussein , Hajj Ali Adel , Tabaja Chadi , Khouri Jack , Anwer Faiz 
Published: June 2023

e20039 Background: Patients with multiple myeloma (MM) of standard risk (SR) cytogenetics generally experience better outcomes compared to high risk (HR) disease. However, it remains poorly understood why outcomes amongst SR MM patients are highly variable, especially after autologous hematopoietic cell transplant (AHCT). Here, we investigated the outcomes of AHCT in SR MM patients who failed multiple therapies pre-AHCT. Methods: We reviewed all MM patients who underwent AHCT at the Cleveland Clinic between January 1, 2011 and January 15, 2021. Demographic characteristics, comorbidities, International Scoring System (ISS) stages, serum and bone marrow studies, pre-AHCT treatments, and maintenance therapy were obtained from electronic medical records. SR MM was considered in patients without t(4;14), t(14;16), t(14;20), del(17p), or gain(1q). Patients were divided into 4 groups of 1, 2, 3 or ≥4 therapies pre-AHCT. The primary outcome studied was median time to either progression or death, reported as time to event (TTE) and determined by Kaplan Meier analysis. Results: We reviewed a total of 517 patients, among whom 279 were determined as SR MM and hence were included in our analysis. Of this cohort, 188 patients received a single line of therapy, 63 patients received 2 lines, 32 patients received 3 lines, and 10 patients received ≥4 lines pre-AHCT. The baseline demographic and clinical characteristics were then compared between the groups and they showed similar age at AHCT (61 vs 60.6 vs 59.6 vs 59.9 years, P=0.8), albumin levels (<3.5 g/dL 22.4 vs 22.8 vs 16.7 vs 50%, P=0.2), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score (≥3 40.4 vs 47.6 vs 65.6 vs 60%, P=0.1), Male preponderance (54.8 vs 65.1 vs 65.6 vs 50%, P=0.4), ethnicity (White 82.4 vs 84.1 vs 78.1 vs 90%, P=0.8), ISS stages (P=0.7), MM immunoglobulin subtype (IgG 28.7 vs 20.6 vs 18.8 vs 30%, P=0.6), on single agent maintenance (8.9 vs 19 vs 13.8 vs 0%, P=0.1), respectively. The only significant differences between the four groups were smoking history (34.9 vs 53.2 vs 40.6 vs 60%, P=0.045) and time from diagnosis to transplant (>12 months 21.3 vs 44.4 vs 75 vs 100%, P<0.0001) reflecting resistance to therapies. Kaplan-Meier analysis for median TTE revealed a significantly shorter median TTE for the ≥4 therapies group at 8 months vs 54.5, 55.9 and 67.7 months for the 1, 2, and 3 pre-AHCT therapies groups. Conclusions: SR MM patients who require ≥4 therapies pre-AHCT have poor outcomes post-transplant. We suggest the use of AHCT early in the course of myeloma treatment given the shorter time to progression as also shown in randomized trials.
In hospital outcomes and mortality predictors of multiple myeloma on stroke hospitalizations: A multivariable logistic regression study on the National Inpatient Sample Database.
Authors: Shah Zunairah , Younas Hafiz Muhammad Waqar , Rehman Mohammad Ebad Ur , Taha Amro , Baloch Ali Shahbaz Shehbaz , Khir Fadi , Badu Irisha , Basit Jawad , Sandhyavenu Harigopal , Ali Shehzad , Anwer Faiz 
Published: June 2023

e20048 Background: Multiple Myeloma (MM) patients have a higher risk of stroke due to a hypercoagulable state. A study by Liu et al. 2014 reported a 1.23 times higher incidence of stroke in MM patients compared to the matched cohort. Another study by Lee et al. 2016 reported a 5-year estimated cumulative incidence rate of 7.45%. Bortezomib therapy is an independent risk factor for stroke. However, data on the inpatient outcomes of MM on stroke hospitalizations is limited. Therefore, we conducted a nationwide population-based study investigating in-hospital outcomes and mortality predictors of MM in stroke hospitalizations. Methods: The national inpatient sample database from 2016-2019 was queried to identify patients with a primary diagnosis of stroke and stratified based on the presence of MM as a secondary diagnosis. The adjusted odds ratios (aOR) of in-hospital outcomes were calculated using multivariable logistic regression using STATA v.17 software. The primary outcome was in-hospital mortality. Results: A total of 2,028,240 weighted hospitalizations with stroke were identified between 2016-2019, of which 4,240 were associated with MM. On adjusted analysis, stroke-MM patients have statistically significant higher odds of in-hospital mortality (aOR 1.33, CI 1.01-1.40, P<0.001). Furthermore, the presence of fluid and electrolyte imbalance, complicated diabetes mellitus, and coagulopathy were found to be independent predictors of mortality. However, the odds of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), and cardiac arrest were similar between stroke patients with and without MM. Bleeding risk was not assessed, given the low sample size. Additionally, no significant statistical difference was found between the two cohorts regarding the length of hospital stay and cost of hospital stay. Conclusions: Stroke patients with MM have significantly higher odds of in-hospital mortality than those without MM. Given the increased mortality risk, physicians should pay particular attention to optimizing the modifiable risk factors of stroke. Large-scale prospective trials are needed to identify the patients at the highest risk. [Table: see text]
Identifying associations between race and gender in the incidence and mortality of patients with multiple myeloma.
Authors: Ghosh Aditya Kumar , McGuire Nicole , Ruiz Vega Ruben , Alaws Hossny , Adewunmi Comfort , Abidoye Oluseyi , Caton Andria P , Johnson Andrew Thomas 
Published: June 2023

e20052 Background: Multiple Myeloma (MM) is a plasma cell malignancy due to proliferation of malignant clonal plasma cells. Prior studies have shown that overall incidence of MM was 8.47 per 100,000 individuals. It has also been seen that the incidence of MM has trended upwards in non-Hispanic white (NHW) males and non-Hispanic blacks (NHB) across all age groups. This retrospective, database-driven population study sought to further assess racial and gender-based differences in the trends of the incidence of MM and mortality from MM. Methods: Data obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry 17 were available to assess trends of multiple myeloma incidence and mortality from 2000 to 2019. Trends were described as average annual percentage change (APC) rates. Results: A total of 102,467 MM patients were identified in this data set; 56,508 (55.1%) were males and 45,949 (44.8%) were female. The distribution of MM by race was as follows (in order from highest to lowest): Non-Hispanic White [NHW] patients was 63.2% (N = 64,776), Non-Hispanic Black [NHB] patients was 18.6% (n = 19,099), Hispanic patients was 11.6 % (11,841), Non-Hispanic Asian [NHA] patients was 5.6% (5,769), and Non-Hispanic American Indian [NHAI]/Alaska Native patients was 0.5% (523). Incidence of MM (cases per 100,000 persons) was highest in males (7.5; 95% CI: 7.5, 7.6) and blacks (13; 95% CI: 12.8, 13.2). Overall trend in the incidence of MM has increased significantly for all gender and ethnicity groups over the period from 2000-2019, except for NHA patients. The incidence-based mortality of MM was highest in male (5.2; 95% CI: 5.2, 5.3) and black (8.7; 95% CI: 8.5, 8.8) patients. The overall incidence-based mortality increased significantly in males APC 4.1% (95% CI: 2.2,5.9; p < 0.001), females APC 3.6% (95% CI, 1.8,5.5; p < 0.001) and all ethnicities - NHW patients APC 4.1%, (95% CI, 2.2,6.0; p < 0.001), NHB (APC 4.2%, 95% CI, 2.1,6.3; P < 0.001), NHAI (APC 4.7%, 95% CI, -2.2,7.2; p < 0.001), NHA (APC 3.0%, 95% CI: 0.8,5.2; P = 0.009) and Hispanic (APC 2.9, 95% CI:1.1,4.7; P = 0.003). Conclusions: Population-based trends in MM incidence and mortality, as reported in this study, were increased commensurate with prior reports. Of note, mortality was noted to be highest amongst the NHB and male populations, indicating a need for further research focused efforts in this potentially high-risk population.
Clinicopathologic features and outcomes associated with induction regimen intensity among older veterans with myeloma.
Authors: Kirby Conor , Atweh George , Rosko Ashley Elizabeth , Friedman Daphne Ruth , Yellapragada Sarvari , Vashistha Vishal 
Published: June 2023

e20054 Background: More than one third of patients diagnosed with multiple myeloma (MM) are 75 years or older. Though registries and clinical trials have conveyed the disease features across myeloma patients and have confirmed improvement in outcomes with increasing number of frontline induction agents, older patients are disproportionately excluded from these studies. We sought to evaluate the disease characteristics and frontline (FL) induction treatment patterns among older Veterans. Methods: The VA’s Corporate Data Warehouse was queried to identify patients who (1) were diagnosed with MM between January 1, 2016 and December 31, 2019, (2) were 75 years or older at the time of diagnosis, and (3) received at least 1 induction regimen within the VA. Each unique record was reviewed in the VA’s Joint Legacy Viewer, an online platform collectivizing Veteran electronic charts nationwide. Data abstraction was performed to ascertain disease type, cytogenetics, stage, and characteristics of treatment regimen(s) by reviewing provider progress notes and treatment notes. Presence of del(17p), t(4;14), t(14;16), t(14;20), or gain 1q by FISH defined high-risk cytogenetics. Median composite progression-free survival (PFS), defined as the interval between date of FL induction initiation and the earliest date of second induction or death, was computed for Veterans based upon number of drugs in their FL induction regimens. Results: A total of 199 Veterans met selection criteria, with a mean age of 83.0 (SD 4.8) years at start of treatment. Of the 84 patients with documented cytogenetics, 44 (52.3%) had high-risk disease, and 6 (7.1%) had 2 or more deleterious cytogenetic findings. The majority (52.8%) of patients received only 1 induction regimen, and only 44 (22.1%) patients received maintenance therapy following frontline induction. 1 patient underwent autologous stem cell transplant, and 1 was referred for chimeric antigen receptor T-cell therapy. Within FL induction regimen, 104 (52.3%) received 2 drugs and 88 (44.2%) received 3 drugs. Induction therapy selection was unrelated to disease stage (p = 0.556) or cytogenetic risk (p = 0.335), but patients 80 years or older were more likely to receive 2-drug therapy (p = 0.012) than those between 75 and 79 years. No difference in median composite PFS was observed between patients receiving 2 drugs (10.1 [4.5 – 21.7] months) and those receiving 3 drugs (10.7 [5.0 – 20.3] months) (p = 0.733) in FL induction regimen. Conclusions: In a real-world study of older Veterans with MM bearing a high rate of high-risk cytogenetics, the median PFS with FL induction is only 10 months, but a more intensive FL 3-drug induction regimen is not more beneficial than a 2-drug. Less intense treatment planning is most reasonable for geriatric patients. Larger investigations evaluating cytogenetic results across Veterans with MM should be considered.