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Abstract Many studies have documented racial, socioeconomic, geographic, and other disparities for United States (US) patients with multiple myeloma pertaining to diagnosis and frontline management. In contrast, very little is known about disparities in the management of relapsed/refractory multiple myeloma (RRMM) despite a plethora of novel treatment options. In this review, we discuss the manifestations of disparities in RRMM and strategies to mitigate their impact. Immunomodulatory drugs can create disparities on many axes, for example inappropriately low dosing due to Duffy-null status as well as time toxicity and financial toxicity from logistical hurdles for socioeconomically vulnerable patients. Access to myeloma expertise at high-volume centers is a critical consideration given the disconnect between how drugs like carfilzomib and dexamethasone are prescribed in trials versus optimized in real-world practice to lower toxicities. Disparities in chimeric antigen receptor T-cell therapy and bispecific antibody therapy span across racial, ethnic, and socioeconomic lines in large part due to their limited availability outside of high-volume centers. Another insidious source of disparities is supportive care in RRMM, ranging from inadequate pain control in Black patients to limited primary care provider access in rural settings. We discuss the rationales and evidence base for several solutions aimed at mitigating these disparities: for example, (1) bidirectional co-management with community-based oncologists, (2) screening for risk factors based on social determinants of health, (3) strategies to build patient trust with regard to clinical trials, and (4) longitudinal access to a primary care provider. As the treatment landscape for RRMM continues to expand, these types of efforts by the field will help ensure that this landscape is equally accessible and traversable for all US patients.

Abstract Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018-2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20–0.43) and TCEs (aHR = 0.62, 95%CI = 0.43–0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18–0.44) and TCEs (aHR = 0.60, 95%CI = 0.39–0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.

Abstract Multiple myeloma (MM) therapeutics have evolved tremendously in recent years, with significant improvement in patient outcomes. As newer treatment options are developed, stem cell transplant (SCT) remains an important modality that provides excellent disease control and delays the progression of disease. Over the years, SCT use has increased overall in the U.S., but two distinct gaps remain, including suboptimal use overall and racial-ethnic disparities. We evaluated the National Cancer Database (NCDB) to study what sociodemographic factors might play a role within a given racial-ethnic group leading to disparate SCT utilization, such that targeted approaches can be developed to optimize SCT use for all. In nearly 112,000 cases belonging to mutually exclusive categories of non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA), and others, we found certain factors including age, comorbidity index, payor type, facility type (academic vs. community) and facility volume to be uniformly associated with SCT use for all the racial-ethnic groups, while gender was not significant for any of the groups. There were several other factors that had a differential impact on SCT utilization among the various race-ethnicity groups studied, including year of diagnosis (significant for NHW, NHB, and Hispanics), income level (significant for NHW and Hispanics), literacy level (significant for NHW and NHB), and geographic location of the treatment facility (significant for NHW and NHA). The suboptimal SCT utilization overall in the U.S. suggests that there may be room for improvement for all, even including the majority NHW, while we continue to work on factors that lead to disparities for the traditionally underserved populations. This study helps identify sociodemographic factors that may play a role specifically in each group and paves the way to devise targeted solutions such that resource utilization and impact can be maximized.

Introduction: While randomized controlled trials remain the reference standard for evaluating treatment efficacy, there is an increased interest in the use of external control arms (ECA), namely in oncology, using real-world data (RWD). Challenges related to measurement of real-world oncology endpoints, like progression-free survival (PFS), are one factor limiting the use and acceptance of ECAs as comparators to trial populations. Differences in how and when disease assessments occur in the real-world may introduce measurement error and limit the comparability of real-world PFS (rwPFS) to trial progression-free survival. While measurement error is a known challenge when conducting an externally-controlled trial with real-world data, there is limited literature describing key contributing factors, particularly in the context of multiple myeloma (MM).Methods: We distinguish between biases attributed to how endpoints are derived or ascertained (misclassification bias) and when outcomes are observed or assessed (surveillance bias). We further describe how misclassification of progression events (i.e., false positives, false negatives) and irregular assessment frequencies in multiple myeloma RWD can contribute to these biases, respectively. We conduct a simulation study to illustrate how these biases may behave, both individually and together.Results: We observe in simulation that certain types of measurement error may have more substantial impacts on comparability between mismeasured median PFS (mPFS) and true mPFS than others. For instance, when the observed progression events are misclassified as either false positives or false negatives, mismeasured mPFS may be biased towards earlier (mPFS bias = −6.4 months) or later times (mPFS bias = 13 months), respectively. However, when events are correctly classified but assessment frequencies are irregular, mismeasured mPFS is more similar to the true mPFS (mPFS bias = 0.67 months).Discussion: When misclassified progression events and irregular assessment times occur simultaneously, they may generate bias that is greater than the sum of their parts. Improved understanding of endpoint measurement error and how resulting biases manifest in RWD is important to the robust construction of ECAs in oncology and beyond. Simulations that quantify the impact of measurement error can help when planning for ECA studies and can contextualize results in the presence of endpoint measurement differences.

Patients with relapsed/refractory multiple myeloma (RRMM) that are refractory to the five most active anti-MM drugs, so-called penta-refractory MM, have historically had dismal outcomes with subsequent therapies. Progressive immune dysfunction, particularly of the T-cell repertoire, is implicated in the development of disease progression and refractory disease. However, the advent of novel immunotherapies such as bispecific antibodies are rapidly changing the treatment landscape and improving the survival outcomes of patients with RRMM. Bispecific antibodies are antibodies that are engineered to simultaneously engage cytotoxic immune effector cells (T cells or NK cells) and malignant plasma cells via binding to immune effector cell antigens and extracellular plasma cell antigens leading to immune effector cell activation and malignant plasma cell destruction. Currently, bispecific antibodies that bind CD3 on T cells and plasma cell epitopes such as B-cell maturation antigen (BCMA), G-protein coupled receptor family C group 5 member D (GPRC5d), and Fc receptor homologue 5 (FcRH5) are the most advanced in clinical development and are showing unprecedented response rates in patients with RRMM, including patients with penta-refractory disease. In this review article, we explore the available clinical data of bispecific antibodies in RRMM and summarize the efficacy, safety, toxicity, clinical outcomes, mechanisms of resistance, and future directions of these therapies in patients with RRMM.

While immunotherapies, such as CAR T therapy and bi-specific antibodies, have revolutionized the treatment of multiple myeloma (MM), patients with AL amyloidosis have been excluded from trials with these agents due to concerns of underlying autonomic, cardiac, and renal dysfunction, leading to potentially fatal toxicities from these therapies. In this communication, we described the outcomes of two patients with AL amyloidosis and concurrent MM with underlying cardiac and/or renal dysfunction who underwent anti-BCMA CAR T cell therapy with ide-cel or cilta-cel, received cytokine release syndrome prophylaxis, and tolerated therapy well with manageable toxicities and achieved a MRD-negative state. We described the preliminary efficacy and safety of CAR T in patients with AL amyloidosis and highlighted the importance of patient selection and medical optimization of cardiac and renal function prior to CAR T.

Abstract Introduction Health information technology (HIT) has the potential to improve healthcare delivery and engagement. Studying racial‐ethnic disparities in HIT engagement will help understand and overcome challenges to healthcare utilization. Methods We undertook a patient‐reported survey among patients with lymphoid malignancies at two campuses of Mayo Clinic, Florida to explore HIT‐related disparities. Variables between Whites and non‐Whites, and non‐Whites from the two campuses were compared. Results The survey was completed by 1004 respondents, with 71% whites, 27% non‐Whites (race‐ethnicity not reported by 2%). Non‐Whites included 30% responders at the main campus and 64% at an inner‐city campus. Whites were significantly older and had higher education, while non‐Whites had lesser access to a computer. Only 51% of non‐Whites were registered to use electronic medical records (EMR) as compared to 72% Whites (p

Abstract Background BCMA-directed CAR T-cell therapy (CAR-T) has altered the treatment landscape of relapsed/refractory (r/r) multiple myeloma, but is hampered by unique side effects that can lengthen hospital stays and increase morbidity. Hematological toxicity (e.g. profound and prolonged cytopenias) represents the most common grade ≥ 3 toxicity and can predispose for severe infectious complications. Here, we examined the utility of the CAR-HEMATOTOX (HT) score to predict toxicity and survival outcomes in patients receiving standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel. Methods Data were retrospectively collected from 113 r/r multiple myeloma patients treated between April 2021 and July 2022 across six international CAR-T centers. The HT score—composed of factors related to hematopoietic reserve and baseline inflammatory state—was determined prior to lymphodepleting chemotherapy. Results At lymphodepletion, 63 patients were HTlow (score 0–1) and 50 patients were HThigh (score ≥ 2). Compared to their HTlow counterparts, HThigh patients displayed prolonged severe neutropenia (median 9 vs. 3 days, p

Abstract There are disparities in outcomes for patients with multiple myeloma (MM). We evaluated the influence of sociodemographic factors on global disparities in outcomes for patients with MM. This rapid evidence assessment (PROSPERO, CRD42021248461) followed PRISMA-P guidelines and used the PICOS framework. PubMed and Embase® were searched for articles in English from 2011 to 2021. The title, abstract, and full text of articles were screened according to inclusion/exclusion criteria. The sociodemographic factors assessed were age, sex, race/ethnicity, socioeconomic status, and geographic location. Outcomes were diagnosis, access to treatment, and patient outcomes. Of 84 articles included, 48 were US-based. Worldwide, increasing age and low socioeconomic status were associated with worse patient outcomes. In the US, men typically had worse outcomes than women, although women had poorer access to treatment, as did Black, Asian, and Hispanic patients. No consistent disparities due to sex were seen outside the US, and for most factors and outcomes, no consistent disparities could be identified globally. Too few studies examined disparities in diagnosis to draw firm conclusions. This first systematic analysis of health disparities in patients with MM identified specific populations affected, highlighting a need for additional research focused on assessing patterns, trends, and underlying drivers of disparities in MM.

Aim: Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. Patients & methods: Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). Results: Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p < 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p < 0.05) versus patients treated with anti-CD20 + chemotherapy. Conclusion: Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

Abstract Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC

IntroductionNewer treatment options for relapsed/refractory multiple myeloma (RRMM) with efficacy and safety profiles that differ from traditional therapies have facilitated personalized management strategies to optimize patient outcomes. In the context of such personalized management, understanding how treatment characteristics influence patients’ preferences is essential. This study assessed patients’ preferences for RRMM treatment attributes and determined trade-offs between potential benefits, administration procedures, and adverse effects.MethodsPatients’ preferences were evaluated using a discrete choice experiment (DCE). Patients with RRMM who reported failing two lines of anti-myeloma treatment (immunomodulatory agent and a proteasome inhibitor [PI]) or ≥ 3 lines (including ≥1 PI, immunomodulatory agent, or anti-CD38 monoclonal antibody), were recruited across the US, UK, Italy, Germany, France, and Spain. DCE attributes and levels were identified using a targeted literature review, a review of clinical data for relevant RRMM treatments, qualitative patient interviews, and input from clinical and myeloma patient experts. The DCE was administered within an online survey from February–June 2022. Preference data were analyzed using an error-component logit model and willingness to make trade-offs for potential benefits, and relative attribute importance scores were calculated.ResultsOverall, 296 patients from the US (n = 100), UK (n = 49), Italy (n = 45), Germany (n = 43), France (n = 39), and Spain (n = 20) participated in the DCE. Mean (standard deviation) age was 63.8 (8.0) years, 84% had a caregiver, and patients had a median of 3 (range: 2–8) prior lines of therapy. Efficacy attributes most influenced patients’ preferences, with increasing overall response rate (25–85%) and overall survival (6 months to 2 years) contributing to ~50% of treatment decision-making. Administration procedures were also considered important to patients. Avoiding individual side effects was considered relatively less important, with patients willing to tolerate increases in side effects for gains in efficacy. Patient characteristics such as rate of disease progression, sociodemographics, or clinical characteristics also influenced treatment preferences.ConclusionPatients with RRMM were willing to tolerate increased risk of side effects for higher efficacy. Preferences and risk tolerance varied between patients, with preference patterns differing by certain patient characteristics. This highlights the importance of shared decision-making for optimal treatment selection and patient outcomes.

Abstract Background Extended first‐line therapy (1LT) has improved clinical outcomes in newly diagnosed multiple myeloma (NDMM). This retrospective study of NDMM patients evaluated the relationship between dose‐attenuation of 1LT and duration of therapy (DOT) and DOT on outcomes. Methods Adults with NDMM not undergoing stem cell transplant (SCT) from January 1, 2012 toMarch 31, 2018 from the Integrated Oncology Network were included; 300 were randomly selected for chart review. 1LT DOT, time to next treatment (TTNT), progression‐free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier analysis. Marginal structural models evaluated relationships between DOT and TTNT, PFS, and OS at 2 years accounting for confounders and survival bias from the time‐dependent nature of DOT. Results Of 300 chart‐reviewed patients, 93 were excluded for incomplete data or meeting exclusion criteria. Among 207 NDMM patients, median age was 74 years; 146 (70.5%) did not receive dose‐attenuation during 1LT. Patients with short DOT were older, frailer, with a higher comorbidity burden, and a significantly lower proportion had an Eastern Cooperative Oncology Group PS = 0. As DOT increased, more patients underwent dose‐attenuation (p

Abstract Patients with chronic lymphocytic leukemia (CLL) with disease progression on ibrutinib have worse outcomes compared to patients stopping ibrutinib due to toxicity. A better understanding of expected outcomes in these patients is necessary to establish a benchmark for evaluating novel agents currently available and in development. We evaluated outcomes of 144 patients with CLL treated at Mayo Clinic with 2018 iwCLL disease progression on ibrutinib. The median overall survival (OS) for the entire cohort was 25.5 months; it was 29.8 months and 8.3 months among patients with CLL progression (n = 104) and Richter transformation (n = 38), respectively. Longer OS was observed among patients with CLL progression who had received ibrutinib in the frontline compared to relapsed/refractory setting (not reached versus 28.5 months; p = 0.04), but was similar amongst patients treated with 1, 2, or ≥3 prior lines (18.5, 30.9, and 26.0 months, respectively, p = 0.24). Among patients with CLL disease progression on ibrutinib, OS was significantly longer when next-line treatment was chimeric antigen receptor T-cell therapy (median not reached) or venetoclax-based treatment (median 29.8 months) compared to other approved treatments, such as chemoimmunotherapy, phosphoinositide 3’-kinase inhibitors, and anti-CD20 monoclonal antibodies (9.1 months; p = 0.03). These findings suggest an unmet need for this growing patient population.

Abstract A clearer understanding of the prognostic implications of t(11;14) in multiple myeloma (MM) is needed to inform current and future therapeutic options. We utilized real-world data from a US database to examine treatment patterns and outcomes in patients by t(11;14) status compared with high- and standard-risk subgroups across different lines of therapy (LoT). This retrospective, observational cohort study used de-identified patient-level information from adults with MM and first-line treatment initiation between January 2011 and January 2020, followed until February 2020. The high-risk cohort comprised patients with high-risk genetic abnormalities per mSMART criteria (including those with co-occurring t(11;14)). Among 6138 eligible patients, 6137, 3160, and 1654 received first-, second-, and third-line treatments, respectively. Of 645 patients who had t(11;14), 69.1% had t(11;14) alone, while 30.9% had co-occurring high-risk abnormalities. Altogether, 1624 and 2544 patients were classified as high- and standard-risk, respectively. In the absence of biomarker-driven therapy, treatment patterns remain similar across LoT in high-risk, t(11;14)+, and standard-risk subgroups. Across all LoT, patient outcomes in the high-risk subgroup were less favorable than those in the t(11;14)+ and standard-risk subgroups. Thus, there is an opportunity for novel therapeutics targeted to t(11;14) and other defined subgroups to personalize MM therapy and optimize patient outcomes.

Abstract: Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10−6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10−12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

Abstract Background The Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB) show improved overall survival (OS) in patients with multiple myeloma (MM) over the last 15 years. This analysis evaluated the validity of the largely community‐based Connect MM Registry as a national reference for MM. Methods Baseline disease characteristics and survival in US newly diagnosed MM patients were examined using the Connect MM Registry as well as SEER and NCDB databases. Baseline characteristics predictive of longer survival in Connect MM were also identified. Results As of February 2017, 3011 patients were enrolled in the Connect MM Registry; 2912 were treated. Median age at time of MM diagnosis and age range were numerically similar from 2010 to 2015 across all 3 registries; SEER had a higher representation of nonwhite racial groups than that in the other 2 registries. OS rates suggest proportionate improvement with year of diagnosis among the 3 registries. A Cox proportional hazards model suggests that younger age (

Abstract Extramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1% of cases and can be differentiated from infectious etiologies based on fluid cytology.

Expert consensus on the potential benefits of early cancer detection does not exist for most cancer types. We convened 10 practicing oncologists using a RAND/UCLA modified Delphi panel to evaluate which of 20 solid tumors, representing >40 American Joint Committee on Cancer (AJCC)-identified cancer types and 80% of total cancer incidence, would receive potential clinical benefits from early detection. Pre-meeting, experts estimated how long cancers take to progress and rated the current curability and benefit (improvement in curability) of an annual hypothetical multi-cancer screening blood test. Post-meeting, experts rerated all questions. Cancers had varying estimates of the potential benefit of early cancer detection depending on estimates of their curability and progression by stage. Cancers rated as progressing quickly and being curable in earlier stages (stomach, esophagus, lung, urothelial tract, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck) were estimated to be most likely to benefit from a hypothetical screening blood test. Cancer types rated as progressing quickly but having comparatively lower cure rates in earlier stages (liver/intrahepatic bile duct, gallbladder, pancreas) were estimated to have medium likelihood of benefit from a hypothetical screening blood test. Cancer types rated as progressing more slowly and having higher curability regardless of stage (prostate, thyroid) were estimated to have limited likelihood of benefit from a hypothetical screening blood test. The panel concluded most solid tumors have a likelihood of benefit from early detection. Even among difficult-to-treat cancers (e.g., pancreas, liver/intrahepatic bile duct, gallbladder), early-stage detection was believed to be beneficial. Based on the panel consensus, broad coverage of cancers by screening blood tests would deliver the greatest potential benefits to patients.

BackgroundSmall cell lung cancer (SCLC) is associated with aggressive biology and limited treatment options, making this disease a historical challenge. The influence of race and socioeconomic status on the survival of stage IV SCLC remains mostly unknown. Our study is designed to investigate the clinical survival outcomes in Black and White patients with stage IV SCLC and study the demographic, socioeconomic, clinical features, and treatment patterns of the disease and their impact on survival in Blacks and Whites.Methods and ResultsStage IV SCLC cases from the National Cancer Database (NCDB) diagnosed between 2004 and 2014 were obtained. The follow-up endpoint is defined as death or the date of the last contact. Patients were divided into two groups by white and black. Features including demographic, socioeconomic, clinical, treatments and survival outcomes in Blacks and Whites were collected. Mortality hazard ratios of Blacks and Whites stage IV SCLC patients were analyzed. Survival of stage IV SCLC Black and White patients was also analyzed. Adjusted hazard ratios were analyzed by Cox proportional hazards regression models. Patients’ median follow-up time was 8.18 (2.37-15.84) months. Overall survival at 6, 12, 18 and 24 months were 52.4%, 25.7%, 13.2% and 7.9% in Blacks in compared to 51.0%, 23.6%, 11.5% and 6.9% in Whites. White patients had significantly higher socioeconomic status than Black patients. By contrast, Blacks were found associated with younger age at diagnosis, a significantly higher chance of receiving radiation therapy and treatments at an academic/research program. Compared to Whites, Blacks had a 9% decreased risk of death.ConclusionOur study demonstrated that Blacks have significant socioeconomic disadvantages compared to Whites. However, despite these unfavorable factors, survival for Blacks was significantly improved compared to Whites after covariable adjustment. This may be due to Blacks with Stage IV SCLC having a higher chance of receiving radiation therapy and treatments at an academic/research program. Identifying and removing the barriers to obtaining treatments at academic/research programs or improving the management in non-academic centers could improve the overall survival of stage IV SCLC.

Abstract Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL, and management is poorly understood. We describe a case of an 81‐year‐old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

Abstract: The objective of the study was to assess racial disparities in the treatment and outcomes among white, African American, and Hispanic patients with multiple myeloma (MM). Patients with an MM diagnosis from the Surveillance Epidemiology and End Results (SEER)–Medicare (2007-2013) database were included. Continuous Medicare enrollment for 6 months before (baseline) and after MM diagnosis was required unless death occurred. Time from MM diagnosis to novel therapy initiation and autologous stem cell transplant (ASCT), overall survival (OS), and MM-specific survival (MSS) was evaluated. Unadjusted and multivariable regressions compared African Americans and Hispanics vs whites. Trends of novel therapy and ASCT use across MM diagnosis years were assessed using linear regression models. The study included 3504 whites, 858 African Americans, and 468 Hispanics. African Americans and Hispanics had a longer time from MM diagnosis to novel therapy initiation vs whites (median: 5.2 and 4.6 vs 2.7 months, respectively). All cohorts had an increasing trend of novel therapy initiation within 6 months of MM diagnosis, particularly whites (all P < .05). Median MSS was significantly longer for African Americans (5.4 years) than whites (4.5 years; P < .05), and was comparable for Hispanics and whites. Median OS was similar overall (2.6-2.8 years). ASCT rate within 1 year of MM diagnosis rose among whites and African Americans (P < .05), but not Hispanics, who were less likely to receive ASCT vs whites. Significant variations in novel therapy and ASCT use were observed among different racial/ethnic groups with MM. Although OS was similar, both African Americans and Hispanics may not be fully benefitting from the introduction of novel therapies, as they receive them later than whites.

Importance: Social media is widely used by various segments of society. Its role as a tool of communication by the Public Health Departments in the U.S. remains unknown. Objective: To determine the impact of the COVID-19 pandemic on social media following of the Public Health Departments of the 50 States of the U.S. Design, Setting, and Participants: Data were collected by visiting the Public Health Department web page for each social media platform. State-level demographics were collected from the U.S. Census Bureau. The Center for Disease Control and Prevention was utilized to collect information regarding the Governance of each State’s Public Health Department. Health rankings were collected from “America’s Health Rankings” 2019 Annual report from the United Health Foundation. The U.S. News and World Report Education Rankings were utilized to provide information regarding the public education of each State. Exposure: Data were pulled on 3 separate dates: first on March 5th (baseline and pre-national emergency declaration (NED) for COVID-19), March 18th (week following NED), and March 25th (2 weeks after NED). In addition, a variable identifying the total change across platforms was also created. All data were collected at the State level. Main Outcome: Overall, the social media following of the state Public Health Departments was very low. There was a significant increase in the public interest in following the Public Health Departments during the early phase of the COVID-19 pandemic. Results: With the declaration of National Emergency, there was a 150% increase in overall public following of the State Public Health Departments in the U.S. The increase was most noted in the Midwest and South regions of the U.S. The overall following in the pandemic “hotspots,” such as New York, California, and Florida, was significantly lower. Interesting correlations were noted between various demographic variables, health, and education ranking of the States and the social media following of their Health Departments. Conclusion and Relevance: Social media following of Public Health Departments across all States of the U.S. was very low. Though, the social media following significantly increased during the early course of the COVID-19 pandemic, but it still remains low. Significant opportunity exists for Public Health Departments to improve social media use to engage the public better.

Dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA.R-EPOCH) is used for upfront treatment of high-risk diffuse large B cell lymphoma (DLBCL). In this study, we compared the outcomes in patients with high-risk DLBCL who received frontline rituximab, cycophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or DA.R-EPOCH immunochemotherapy. Outcomes and treatment-related cost were analyzed. DLBCL with one of the following features were included in the study: MYC ± BCL2 or BCL6 rearrangement by FISH or MYC overexpression by immunohistochemistry, Ki67 index ≥ 80% or nongerminal center immunophenotype, tumor measuring ≥5 cm and NCCN- IPI score ≥4. A total of 80 patients were treated with R-CHOP (n = 52, 65%) or DA.R-EPOCH (n = 28, 35%), with a median follow-up of 11.2 months (range: 0.7–151.3 months). The hazard ratios (HRs) for progression-free survival and overall survival were 0.79 [95% confidence interval (CI) 0.28%–2.29%, p = 0.67] and 0.86 (95% CI 0.26%–2.78%, p = 0.80), respectively for DA.R-EPOCH compared to R-CHOP. The total mean cost was USD106,940 ± USD39,351 and USD58,509 ± 24,588 for DA.R-EPOCH and R-CHOP respectively (p < 0.001). In our analysis, DA.R-EPOCH resulted comparable clinical outcomes and increased treatment-related expenses compared to R-CHOP in high-risk DLBCL.

Extramedullary multiple myeloma is defined by the presence of plasma cell infiltration outside of the bone marrow. It is associated with a poor prognosis and resistance to therapy and is often associated with high-risk cytogenetics. Aggressive relapsed and refractory extramedullary multiple myeloma is often treated with salvage infusional chemotherapy to achieve rapid disease control. Commonly used regimens include DCEP, CVAD, and VTD-PACE. While VTD-PACE contains bortezomib and thalidomide which have potent antimyeloma activity, the advent of novel agent therapy with proteasome inhibitors and immunomodulatory agents being used in the first-line setting has resulted in many patients being refractory to bortezomib by the time they are treated with VTD-PACE. Herein, we discuss two cases of aggressive relapsed, high-risk, bortezomib-refractory extramedullary multiple myeloma treated with KRD-PACE and review the available clinical data on salvage chemotherapy regimens used in relapsed refractory myeloma.

Abstract: Approximately one third of cancer patients suffer from comorbid mood disorders that are associated with increased cost and poorer outcomes. The majority of patients with multiple myeloma (MM) are treated with corticosteroids; as many as three fourths of those taking corticosteroids develop neuropsychiatric complications, likely increasing morbidity and cost of care. MM patients diagnosed between 1991 and 2010 and reported in the Surveillance Epidemiology, and End Results-Medicare database were characterized as MM-Only, MM+Psychiatric (any psychiatric condition, preexisting or post-MM), or MM+Depression (depression as the only psychiatric diagnosis, preexisting or post-MM). Differences in demographic characteristics, occurrence of clinical myeloma-defining events (MDEs), health care utilization (inpatient, outpatient, ambulatory claims), and cost of care during the first 6 months of MM diagnosis were analyzed. Psychiatric comorbidities were reported more frequently in females, and racial minorities had lower rates of psychiatric comorbidities. All clinical MDEs were more common in the MM+Psychiatric and MM+Depression groups; within them, the majority were more common in patients diagnosed with the psychiatric condition or depression after MM compared with it being a preexisting condition. Health care utilization in all treatment settings was higher in those with psychiatric comorbidities. Cost of care within the first 6 months after MM diagnosis was significantly higher in the MM+Psychiatric and MM+Depression groups. This increase in cost was more pronounced for patients from racial minorities diagnosed with a psychiatric condition, including depression. Psychiatric comorbidities significantly impact the clinical presentations, health care utilization, and cost among patients with MM. These findings need to be addressed for improved survivorship of MM patients.

Obinutuzumab is used for the treatment of chronic lymphocytic leukemia. So far there are no data of using this for retreatment in patients who have received it previously. We introduced obinutuzumab for the retreatment in a chronic lymphocytic leukemia patient, who had first achieved partial remission with it and eventually relapsed over a course of 2.5 years. After retreatment with single-agent obinutuzumab, the patient achieved a partial remission again within one cycle and continues to maintain the response status. This case is a platform for considering obinutuzumab as a viable option for retreatment of chronic lymphocytic leukemia patients who have received it before, similar to the pattern of use for other anti-CD20 monoclonal antibodies in this disease, including rituximab.

An Extramedullary Plasmacytoma (EMP) is characterized by a neoplastic proliferation of clonal plasma cells outside the medullary cavity. EMPs are a rare occurrence compared to other malignant plasma cell disorders and account for approximately 3-5% of plasma-cell neoplasms. Although most cases of EMP are not immediately life threatening at diagnosis, EMPs can progress to Multiple Myeloma (MM) and thus, warrant monitoring. Currently, there are no standard guidelines for when and how to monitor patients who are diagnosed with or treated for a solitary plasmacytoma. We present a case of solitary EMP who was treated adequately and definitively but developed a distinct, non-contiguous subsequent solitary EMP and was only discovered due to surveillance 18F-Fludeoxyglucose Positron Emission Tomography (18F-FDG) (PET) scan. Uniform surveillance guidelines should be developed and the potential benefits of PET and other imaging techniques as well as their cost should be considered.

Granulocytic Sarcomas (GS) also called as Myeloid Sarcomas (MS) or chloromas are the representatives of extramedullary infiltrates of immature myeloid cells including myeloblasts, promyelocytes and myelocytes. Primary cardiac malignancies per se are rare and infiltration of cardiac muscles by secondary malignant cells is also an uncommon finding. Out of these cardiac tumors, contribution of Cardiac Myeloid Sarcoma (CMS) is even more smaller thereby limiting our knowledge about this rare entity. Because of its very lower incidence, an exact guideline for diagnosis and management is still missing and usually haematologists around the world are treating CMS based on their clinical acumen. Aim of this review is to briefly discuss the presenting clinical feature, differential diagnosis, diagnostic workup and management based on published articles related to CMS till date.

Dysferlinopathy is an uncommon, progressive muscular dystrophy that has a wide phenotypic variability and primarily supportive management (Nguyen et al., 2007; Narayanaswami et al., 2014). Amyloid myopathy is a distinct, rare disorder that can present similarly to inflammatory myopathies and requires a high clinical suspicion for early intervention to prolong survival. Amyloid myopathy is typically associated with other systemic manifestations of amyloidosis, but rare cases of isolated amyloid myopathy have been described (Mandl et al., 2000; Hull et al., 2001). Positive Congo red stains on tissue biopsy remain the gold standard for diagnosis (Spuler et al., 1998; Karacostas et al., 2005). A high clinical suspicion and meticulous diagnostic workup that includes novel techniques are necessary for identifying these rare disorders. We report a middle-aged man with progressive leg muscle weakness who was initially treated as having amyloid myopathy but was later diagnosed as having dysferlinopathy by Whole Exome Sequencing (WES) analysis. We also report a novel missense mutation (c.959G>C) to help correlate in any patient with presumed dysferlinopathy and to add to the already known genotype of this disorder.

Waldenströms macroglobulinemia (WM) is a subtype of Non-Hodgkin's lymphoma in which the tumor cell population is markedly heterogeneous, consisting of immunoglobulin-M secreting B-lymphocytes, plasmacytoid lymphocytes and plasma cells. Due to rarity of disease and scarcity of reliable preclinical models, many facets of WM molecular and phenotypic architecture remain incompletely understood. Currently, there are 3 human WM cell lines that are routinely used in experimental studies, namely, BCWM.1, MWCL-1 and RPCI-WM1. During establishment of RPCI-WM1, we observed loss of the CD19 and CD20 antigens, which are typically present on WM cells. Intrigued by this observation and in an effort to better define the immunophenotypic makeup of this cell line, we conducted a more comprehensive analysis for the presence or absence of other cell surface antigens that are present on the RPCI-WM1 model, as well as those on the two other WM cell lines, BCWM.1 and MWCL-1. We examined expression of 65 extracellular and 4 intracellular antigens, comprising B-cell, plasma cell, T-cell, NK-cell, myeloid and hematopoietic stem cell surface markers by flow cytometry analysis. RPCI-WM1 cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced expression of CD28, CD38 and CD184, antigens that were differentially expressed on BCWM.1 and MWCL-1 cells. Due to increased expression of CD184/CXCR4 and CD38, RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or anti-CD38 targeted therapies that are actively being developed for treatment of hematologic cancers. Overall, differences in surface antigen expression across the 3 cell lines may reflect the tumor clone population predominant in the index patients, from whom the cell lines were developed. Our analysis defines the utility of the most commonly employed WM cell lines as based on their immunophenotype profiles, highlighting unique differences that can be further studied for therapeutic exploit.