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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.

Background: HIT has the potential to improve the health of individuals and the performance of providers, yielding improved quality, cost savings, and greater engagement by patients. Minorities face a variety of financial and nonfinancial barriers to obtaining appropriate and timely health care. Studying the behavior of minority patients will help understand the specific challenges to HIT adoption and engagement in patients and their caregivers. We undertook a patient-reported survey to explore these factors and understand any underlying disparities. Methods: A 21-question paper-based anonymous questionnaire addressing the responder's attitudes, understanding and needs of the electronic medical record (EMR) was used. This was administered to adult patients with lymphoid malignancies and their caregivers at two campuses of Mayo Clinic in Florida (San Pablo and inner-city; Riverside). Categorical and continuous variables between white and minority responders as well as minority responders from the two campuses were compared using the Chi-square test and U Mann Whitney with a significance level of 0.05. Results: The survey was completed by 1004 patients and caregivers. Average time taken to complete the survey was approximately 11 minutes. Of the responders, 716 (71%) were whites and 271 (27%) were minorities, with race-ethnicity not reported by 17 (2%). Among minorities, 30% (n=80) were seen at San Pablo and 64% (n=173) at the Riverside campus, with 6% at a multiple myeloma patient-caregiver symposium. Whites were older (median age 66 vs. 62 years, p<0.001) and had higher education (undergraduate or higher 60% vs. 52%, p=0.023) as compared to minorities. Minority survey responders had lesser access to a computer (84% vs. 92%, p<0.001) or a smartphone (85% vs. 89%, p=0.08). (Figure 1a) Exploring HIT awareness showed that only 51% of minorities were registered to use the EMR as compared to 72% whites (p<0.001) and a lesser number of minorities even knew that they could access their medical records electronically (81% vs. 92%, p<0.001). even among those registered to use the EMR, 13% minorities reported never using the EMR as compared to 4% whites (p<0.001). Encouragingly, a higher willingness to learn about and use the EMR was noted among minorities who were more interested in knowing how to access the EMR (43% vs. 36%, p=0.04), would increase the use of EMR if someone explained how to use it (17% vs. 10%, p=0.002), and if someone explained about test results (14% vs. 6%, p<0.001). (Figure 1b) Comparing minorities among the two campuses, those from the San Pablo campus were older (67.5 yrs. vs. 57 yrs., P<0.001), had higher level of education (undergraduate or higher in 66% vs. 47%, p=0.005) and a higher number had access to a computer (94% vs. 78%, P=0.001) as compared to those from the inner-city Riverside. (Figure 2a) Minorities from the Riverside campus were less likely to be aware of the current HIT EMR (75% vs. 93%, p<0.001), were significantly less likely to have registered for the patient EMR portal (38% vs. 76%, p<0.001) and never used the EMR even if registered for it (22% vs. 7%, p=0.01) as against those from the San Pablo campus. Minorities at the Riverside campus had a higher interest in knowing how to access the EMR (47% vs. 33%, p=0.03). Linguistic barriers were more striking in the inner-city Riverside campus where a higher proportion of minority survey responders noted that it would help if the EMR was in their primary language (66% vs. 48%, p=0.006). (Figure 2b) Conclusions: Minorities continue to struggle with suboptimal utilization of healthcare system including that of HIT. There are barriers related to access, awareness, language and understanding of HIT that prevent the integration and participation of racial-ethnic minorities in the healthcare system to a full extent. It is important to qualify the minorities better, since there exist HIT utilization disparities even within the minorities from different areas representing socioeconomic and demographic differences. Efforts need to be made at several levels to help the minorities overcome educational, access and linguistic barriers so that they can benefit from advancements in the healthcare system. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; Takeda: Consultancy. Manochakian:Novocure: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Guardant Health: Membership on an entity's Board of Directors or advisory committees. Chanan-Khan:AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding.

Background: Survival of patients with MM has improved significantly over recent years due to therapeutic advancements. Population-level data has shown that a substantial proportion of MM patients may die early after their diagnosis and real-world evidence regarding early mortality (≤6 months after MM diagnosis) has been conflicting. We evaluated the trends, causes and predictors of early mortality among newly diagnosed MM (NDMM) patients in the real world. Methods: We used Surveillance Epidemiology and End Results (SEER) database, to identify all adult patients (age ≥ 18 years) who were diagnosed of MM from 1975 to 2015. Data on age, gender, geographical regions, year of diagnosis, survival time, vital status at 6 months after diagnosis and cause of death (COD) were extracted. Ages were categorized as quartiles while period of diagnosis for multivariate analysis were categorized by running a joinpoint analysis separately for the all-cause and myeloma-specific mortality. To look at trends in early mortality, we estimated proportion of deaths for each year and plotted it as a scatterplot against the year of diagnosis and fitted it in the join point regression model by applying the NCI's Join point Regression Program, Version 4.5.0.1. By this method we identified the year(s) when a trend change was produced, calculated the annual percentage change (APC) in rates between trend-change points, and the average annual percentage change (AAPC) in the whole period studied. To correct for known errors with COD attribution, we applied a special COD variable which has been recently developed by the SEER program to indicate if the death was due to the primary cancer diagnosis or other causes. A multivariate analysis was conducted to analyze the predictors of all-cause and myeloma-specific mortality within 6 months by fitting into logistic regression model. Results: Of 90,975 NDMM patients, early mortality due to any cause was noted in 18,810 (20.7%). For the whole cohort, median age was 68 years, majority of the patients were males (53.1%), of non-Hispanic white (NHW) race/ethnicity (65.5%) and were diagnosed in SEER registries in the western region (53.9%). An overall survival (OS) of ≤6 months was seen for approximately 22% of NHW but 18% of non-Hispanic blacks (NHB) and Hispanics. OS of ≤6 months was seen in 10% of patients in the first quartile of age (<60 years) as compared to 36% of patients in the 4th quartile (≥78 years). By geographical regions, 23.3% of MM patients in the Midwest had ≤6-month OS as compared to only 18.4% in the Northeast. The most common early mortality COD was MM in 74.7% of the patients, followed by cardiovascular (11.9%), other (8.8%) and infectious causes (3.1%). The overall pattern of COD at 6 months was similar to COD at any time in the whole cohort. Joinpoint regression analysis of trends data resulted in 1 joinpoint for all-cause 6-month mortality while 2 joinpoints were noticed for myeloma-specific mortality (Figure 1). A steep decline in mortality was noticed in the more recent time periods for both, all-cause (2006-2015) and myeloma-specific (2003-2015) mortality rates with an AAPC of 3.93 (95%CI p<0.001) for all-cause and 3.95 (95%CI p<0.001) for myeloma-specific mortality. Prior to 2006, the decrease in all-cause mortality was only modest whereas decrease in myeloma-specific mortality witnessed a sharp decline from 1975-1987 as well. On MVA, advanced age (p<0.001), NHW race/ethnicity and Midwest geographic region (p<0.001) were associated with higher likelihood of mortality while female gender (p<0.001), more recent period of diagnosis (p<0.001), and "other" races (not NHW, NHB or Hispanics) (p<0.001) were associated with lower risk of mortality. Conclusion: Our results show that early mortality due to MM remains high despite therapeutic improvements and there are significant gender, racial and geographic disparities for this phenomenon. However, significant declines in all-cause and MM-specific early mortality in the more recent times are promising. The risk of early mortality is higher among men, older patients, NHW and Midwest region. A focus on interventions to reduce early mortality, including early diagnosis, use of efficacious anti-MM therapy and aggressive supportive care should be directed at groups with high-risk for early mortality from MM. Disclosures Chanan-Khan: Millennium: Research Funding; Ascentage: Research Funding; AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment. Ailawadhi:Celgene: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy; Cellectar: Research Funding; Janssen: Consultancy, Research Funding.

Despite the evolution of the therapeutic arsenal for the treatment of multiple myeloma (MM) over the past decade, autologous stem-cell transplantation (ASCT) remains an integral part of the treatment of patients with both newly diagnosed and relapsed MM. The advent of novel therapies, such as immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies, has led to unprecedented levels of deep hematologic responses. Nonetheless, studies show that ASCT has an additive effect leading to additional deepening of responses. As the therapeutic agents for MM continue to evolve, the timing, duration, and sequence of their use in combination with ASCT will be crucial to understand to obtain the deepest response and survival benefit for patients with MM. This review aims to discuss the role of ASCT for the management of MM, with a particular focus on the role of ASCT in the context of novel therapies and minimal residual disease.

Abstract Background Gastric variceal bleeding carries significant mortality in the setting of portal hypertension. Among the endoscopic treatment options, endoscopic ultrasound (EUS)-guided glue and/or coil injection is a novel approach, but its role in the treatment of gastric varices is not established due to a lack of robust data. Methods We conducted a comprehensive search of several databases (inception to June 2019) to identify studies evaluating EUS in the treatment of gastric varices. Our primary goals were to estimate the pooled rates of treatment efficacy, obliteration and recurrence of gastric varices, early and late rebleeding, and adverse events with EUS-guided therapy in gastric varices. We also searched for studies that evaluated direct endoscopic glue (END-glue) injection for treatment of gastric varices, and used the pooled rates as comparators. Results 23 studies (851 patients) evaluating EUS-guided therapy were included. The pooled treatment efficacy was 93.7 % (95 % confidence interval [CI] 89.5 – 96.3, I 2 = 53.7), gastric varices obliteration was 84.4 % (95 %CI 74.8 – 90.9, I 2 = 77), gastric varices recurrence was 9.1 % (95 %CI 5.2 – 15.7, I 2 = 32), early rebleeding was 7.0 % (95 %CI 4.6 – 10.7, I 2 = 0), and late rebleeding was 11.6 % (95 %CI 8.8 – 15.1, I 2 = 22). The rates were comparable to END-glue therapy (28 studies, 3467 patients) except for obliteration, which was significantly better with EUS-guided therapy. On subgroup analysis, EUS-coil/glue combination showed superior outcomes. Conclusions EUS-guided therapy demonstrated clinical efficacy for treatment of gastric varices in terms of obliteration, recurrence, and long-term rebleeding, and may be superior to END-glue.

Multiple myeloma (MM) treatment has advanced significantly over the last 2 decades. In most patients, the disease course has been altered from early fatality to chronic morbidity with multiple lines of treatment. The MM treatment paradigm has shifted toward treating patients before end-organ damage occurs. Thus, timeliness of treatment initiation in this era might improve patient outcomes. This is the first report to our knowledge analyzing disparities and trends in treatment timeliness of patients with MM using the National Cancer Database. Multiple factors affected the timing of treatment initiation in MM and disparities were found. We noted that initiation of treatment was delayed in women (odds ratio [OR], 1.15; 95% CI, 1.1 to 1.2) and blacks (OR, 1.21; 95% CI, 1.14 to 1.28; reference, whites) and in patients diagnosed in more recent years (2012-2015; OR, 1.15; 95% CI, 1.1 to 1.22; reference, 2004-2007). Patients were likely to start treatment earlier if they were age ≥ 80 years (OR, 0.83; 95% CI, 0.76 to 0.9; reference, age < 60 years), were uninsured (OR, 0.81; 95% CI, 0.72 to 0.91; reference, private insurance), had Medicaid (OR, 0.87; 95% CI, 0.79 to 0.95; reference, private insurance), were treated in a comprehensive community cancer program (OR, 0.7; 95% CI, 0.65 to 0.77; reference, community cancer program), lived in a location other than the US Northeast, or had a higher Charlson comorbidity score. Patient education and income levels did not affect time to treatment initiation. Particular aspects of these disparities could be explained by our current health care system and insurance rules, whereas others need to be investigated more deeply.

ABSTRACT Aims Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF. Methods and results Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = −12.21% (−15.47, −8.95); P &lt; 0.001], LA conduit [WMD = −5.68% (−8.56, −2.79); P &lt; 0.001], and pump [WMD = −11.07% (−14.81, −7.34); P &lt; 0.001] emptying fractions compared with controls. LA reservoir [WMD = −13.38% (−16.07, −10.68); P &lt; 0.001], conduit [WMD = −4.09% (−6.77, −1.42); P = 0.003], and pump [WMD = −3.53% (−4.47, −2.59); P &lt; 0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization. Conclusions Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies.