Survival Differences in Men and Women With Primary Malignant Cardiac Tumor: An Analysis Using the Surveillance, Epidemiology and End Results (SEER) Database From 1973 to 2015.

Background No data are available on sex disparities in prevalence and survival for primary malignant cardiac tumors (PMCT). This study aimed to compare male and female PMCT prevalence and long-term survival rates. Methods and Results We utilized the Surveillance, Epidemiology, and End Results (SEER) 18 database from the National Cancer Institute for all PMCTs diagnosed between 1973 and 2015. From a total of 7 384 580 cases of cancer registered in SEER, we identified 327 men and 367 women with PMCTs. The majority (78%) of patients were white. Sarcoma was the most common type of PMCT in both men and women (≈60%). Individuals diagnosed with lymphoma exhibited better survival than those with other types of PMCTs. Men were diagnosed at a younger age than women; however, there was no significant difference in overall survival between the sexes. Men diagnosed with PMCT between the ages of 51 and 65 years demonstrated prolonged survival compared with those diagnosed at younger or older ages. There was no difference in survival rates among women based on age at diagnosis. Conclusions PMCTs are rare in both men and women. Tumors tend to be diagnosed at an earlier age in men compared with women, but there is no sex disparity in survival rate. Sarcoma is the most common type of PMCT, and lymphoma is associated with the highest survival rate among both sexes.

Monoclonal antibody utilization characteristics in patients with multiple myeloma.

This study analyzed 91 multiple myeloma patients who received two monoclonal antibodies, Daratumumab and Elotuzumab, over a year and report the adverse event profile, infusion practices and utilization of these drugs in the real world. All current reported data on monoclonal antibodies is from clinical trials, without any real-world experience. Patients from Mayo Clinic Florida or Arizona diagnosed with relapsed or refractory multiple myeloma who were treated with Daratumumab or Elotuzumab alone or in combination between 1 January 2016 and 31 December 2016 were included in the analysis. Daratumumab-treated patients (n = 78) were more heavily pre-treated than that in published clinical trials, whereas the elotuzumab patient (n = 13) profile was similar to that published before. Infusion time was on average 2 hours less than the prescribing guidelines and premedication use varied noticeably after the initial monoclonal antibody infusion, with an overall decrease over time. We noted higher than reported haematologic adverse events, especially neutropenia and fewer non-haematologic adverse events. 91.7% infusion-related reactions were observed during the first monoclonal antibody infusion, with a subsequent decrease. All infusion-related reactions were grade 2 or less, and none of the patients discontinued treatment due to infusion-related reactions. Baseline allergy profile or laboratory tests were not associated with the likelihood of developing monoclonal antibody-related infusion-related reactions. The real-world safety profile of monoclonal antibodies showed varying adverse event patterns than those reported in previous clinical trials. The infusion-related reaction patterns were similar to previous reports. Despite changes in premedication regimens safety was maintained in succeeding infusions. Such treatment utilization data is vital to broaden our knowledge of approved therapeutic agents and maximize their benefits for patients.

Surgical septal myectomy for relief of dynamic obstruction in Anderson-Fabry Disease.

Patients with Anderson-Fabry Disease (AFD) and severe left ventricular hypertrophy complicated by left ventricular outflow tract (LVOT) obstruction may benefit from surgical septal myectomy (SSM). Mid- and late outcomes following surgery have not been established, and we sought to better characterize postoperative outcomes following septal myectomy. Between January 2011 and June 2017, 7 patients (6 females) with AFD underwent SSM. The median (range) age at the time of surgery was 53 (37-72) years; 4 patients had a positive family history of AFD and a preoperative diagnosis of AFD. Extracardiac features suggestive of AFD were present in 3 patients and all but 1 (female) had reduced α-galactosidase A activity. All patients had severe left ventricular hypertrophy and LVOT obstruction on transthoracic echocardiography. Preoperatively, all patients were severely symptomatic with New York Heart Association (NYHA) class III symptoms. There was no early mortality following surgery. The median in-hospital length of stay was 5 (4-7) days with 6 patients reporting NYHA class II or less symptoms at 3 month follow-up. Long-term outcomes were favorable with 4 patients reporting sustained NYHA class II or less symptoms, but 2 patients had recurrence of NYHA class III symptoms without evidence of recurrent LVOT obstruction. In conclusion, SSM appears to provide favorable short- and long-term relief of severe, symptomatic LVOT obstruction but may not alter progression of Fabry cardiomyopathy.

Targeting CD38 Enhances the Antileukemic Activity of Ibrutinib in Chronic Lymphocytic Leukemia.

PURPOSE: CD38 has emerged as a high-impact therapeutic target in multiple myeloma, with the approval of daratumumab (anti-CD38 mAb). The clinical importance of CD38 in patients with chronic lymphocytic leukemia (CLL) has been known for over 2 decades, although it's relevance as a therapeutic target in CLL remains understudied. EXPERIMENTAL DESIGN: We investigated the biological effects and antitumor mechanisms engaged by daratumumab in primary CLL cells. Besides its known immune-effector mechanisms (antibody-dependent cell-mediated cytotoxicity, complement-dependent death, and antibody-dependent cellular phagocytosis), we also measured direct apoptotic effects of daratumumab alone or in combination with ibrutinib. In vivo antileukemic activity was assessed in a partially humanized xenograft model. The influence of CD38 on B-cell receptor (BCR) signaling was measured via immunoblotting of Lyn, Syk, BTK, PLCγ2, ERK1/2, and AKT. RESULTS: In addition to immune-effector mechanisms; daratumumab also induced direct apoptosis of primary CLL cells, which was partially dependent on FcγR cross-linking. For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCγ2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib. In comparison to single-agent treatment, the combination of ibrutinib and daratumumab resulted in significantly enhanced anti-CLL activity in vitro and significantly decreased tumor growth and prolonged survival in the in vivo CLL xenograft model. CONCLUSIONS: Overall, our data demonstrate the antitumor mechanisms of daratumumab in CLL; furthermore, we show how cotargeting BTK and CD38 lead to a robust anti-CLL effect, which has clinical implications.

Survival Differences in Women and Men After Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.

Importance: Recent data indicate that women with hypertrophic cardiomyopathy (HCM) are older and more symptomatic at presentation and have worse clinical outcomes than men. However, to our knowledge, there are no large studies of the association of patient sex with outcomes after surgical myectomy. Objective: To analyze preoperative characteristics and overall survival of women and men undergoing septal myectomy for obstructive HCM. Design, Setting, and Participants: This retrospective, single-center study included the clinical data of adult patients who underwent septal myectomy from January 1961 through April 2016. Data analysis occurred from December 2017 to December 2018. Exposures: Septal myectomy. Main Outcomes and Measures: Survival. Results: A total of 2506 adults were included; 1379 patients (55.0%) were men. At the time of surgery, women were older, with median (IQR) age of 59.5 (46.6-68.2) years vs 52.9 (42.9-62.7) years in men (P < .001). Women were more likely to have New York Heart Association class III or IV status at presentation (women, 1023 [90.8%]; men, 1169 [84.8%]; P < .001) and more severe obstructive physiology, as reflected in higher resting left ventricular outflow tract gradients (women, 67.0 [36.0-97.0] mm Hg; men, 50.0 [23.0-81.0] mm Hg; P < .001). Women also had a greater likelihood of having moderate or severe mitral regurgitation (606 [55.2%]) than men (581 [43.1%]; P < .001) and higher right ventricular systolic pressure (women, 36.0 [30.0-46.0] mm Hg; men, 33.0 [28.0-39.0] mm Hg; P < .001). The unadjusted overall survival was lower in women, corresponding to a median 3.9-year shorter survival than men (median [IQR] survival time: women, 18.2 [12.1-27.2] years; men, 22.1 [15.1-32.5] years; P < .001). In a multivariable Cox regression analysis, however, the association between sex and mortality was attenuated and not significant after controlling for other baseline variables (hazard ratio, 0.98 [95% CI, 0.76-1.26]; P = .86). Among the covariates in the model, older age at surgery (adjusted hazard ratio [aHR], 3.09 [95% CI, 2.12-4.52]; P < .001), higher body mass index (aHR, 1.22 [95% CI, 0.90-1.66]; P < .001), greater NYHA class (aHR, 2.31 [95% CI, 1.03-5.15]; P = .04), and presence of diabetes prior to surgery (aHR, 1.57 [95% CI, 1.10-2.24]; P = .01) were each independently associated with increased mortality. Operations performed later in the study period (2013 vs 2004) were associated with decreased mortality (aHR, 0.82 [95% CI, 0.55-1.22]; P = .001). Conclusions and Relevance: In this large cohort of surgical patients with obstructive HCM, we observed significant differences at clinical presentation between women and men, in that women were older and more symptomatic. However, after adjustment for important baseline prognostic factors, there was no survival difference after septal myectomy by sex. Improved care of women with obstructive HCM should focus on early identification of disease and prompt surgical referral of appropriate patients who do not respond to medical treatment.

Myectomy and Left Atrial-to-Left Ventricular Conduit for Severe Calcific Mitral Stenosis and Hypertrophic Cardiomyopathy.

Severe calcific mitral valve stenosis can rarely occur concomitantly with obstructive hypertrophic cardiomyopathy. In these patients, surgical decalcification of the stenotic mitral valve followed by mitral valve replacement carries substantial operative risk and may result in paravalvular leakage, atrioventricular groove disruption, and excessive bleeding. We report two cases of obstructive hypertrophic cardiomyopathy with severe calcific mitral valve stenosis successfully treated with concomitant transaortic septal myectomy and bypass of the stenotic mitral valve with the use of a valved left atrial-to-left ventricular conduit.

Racial disparity in utilization of therapeutic modalities among multiple myeloma patients: a SEER-medicare analysis.

Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial-ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER-Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time-dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4-year follow-up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African-Americans (P < 0.01), higher thalidomide use among Hispanics and Asians (P < 0.01), and lower bortezomib use among Asians (P < 0.01). Hispanics had the highest median number of days to first dose of bortezomib (P = 0.02) and the lowest utilization of SCT (P < 0.01). Hispanics and Asians were the only groups without notable increases in lenalidomide and bortezomib use, respectively. SCT utilization increased over time for all except African-Americans. SCT use within the first year after diagnosis was associated with better overall survival (HR 0.52; 95% CI: 0.4-0.68), while bortezomib use was associated with inferior survival (HR 1.14; 95% CI 1.02-1.28). We noted considerable variability in MM therapeutics utilization with seeming inequity for racial-ethnic minorities. These trends should be considered to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all races.

Equal Treatment and Outcomes for Everyone with Multiple Myeloma: Are We There Yet?

Multiple myeloma treatment has changed tremendously over recent years leading to overall improvement in patient outcomes. With therapeutic advancements, patient care has become increasingly complex and variability is seen in healthcare delivery as well as outcomes when various patient subgroups are analyzed based on sociodemographic factors. It is imperative to understand this variability so that while overall the outcomes get better, specific focus is placed on subgroups that may remain disadvantaged and may not be able to fully access the advancements in therapeutics. Research in multiple myeloma has specifically looked at several such patient subgroups based on socioeconomic status, age, race/ethnicity, insurance carrier, and geographic location that may affect healthcare utilization and patient outcomes. Exploring and understanding these would certainly help address disparities and lead to further equity in healthcare access and, hopefully, patient outcomes.