Trends in multiple myeloma presentation, management, cost of care, and outcomes in the Medicare population: A comprehensive look at racial disparities.

BACKGROUND: Outcomes have improved significantly in multiple myeloma (MM), but racial disparities in health care access and survival exist. A comprehensive analysis exploring MM care and racial disparities is warranted. METHODS: Patients with MM from 1991 to 2010 in the Surveillance, Epidemiology, and End Results-Medicare database were evaluated for racial trends in clinical myeloma-defining events (MDEs), the receipt of treatment (drugs and stem cell transplantation; [SCT]), the cost of care, and overall survival (OS). RESULTS: Among 35,842 patients, the frequency of all MDEs at diagnosis increased over time; whereas, in recent years (2006-2010), all MDEs with the exception of renal dialysis decreased. Blacks had highest rates for all MDEs except bone fractures, which were highest in whites. Over time, the proportion of patients who received any treatment, multiple agents, and SCT increased significantly, and the largest increase was observed in the receipt of immunomodulatory drugs and steroids. There was greater receipt of bortezomib and SCT among whites and blacks and higher receipt of immunomodulatory drugs among Hispanics and Asians (P < .001). Medicare claims were highest during first 6 months after MM diagnosis for blacks and at any time after MM diagnosis for Hispanics. Over time, Medicare claims increased most steadily for Hispanics (P < .001). Hypercalcemia, renal dysfunction, and bone fractures were associated with inferior OS. Blacks and Asians had superior OS compared with whites, but racial differences in OS became less pronounced during 2006 through 2010 (P = .182) compared with prior years (P < .01). Better OS was noted among patients who had higher median incomes. CONCLUSIONS: The current results indicate that there have been significant changes in the management of patients with MM over time and provide an in-depth understanding of the factors that may help explain racial disparities. Cancer 2018;124:1710-21. © 2018 American Cancer Society.

Targeting CD38 with daratumumab is lethal to Waldenström macroglobulinaemia cells.

CD38 is expressed on Waldenström macroglobulinaemia (WM) cells, but its role as a therapeutic target remains undefined. With recent approval of the anti-CD38 monoclonal antibody, daratumumab (Dara), we hypothesized that blocking CD38 would be lethal to WM cells. In vitro Dara treatment of WM cells (including ibrutinib-resistant lines) elicited antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cell phagocytosis (ADCP) and direct apoptosis. In vivo, Dara treatment was well tolerated and delayed tumour growth in RPCI-WM1-xenografted mice. CD38 is reported to augment B-cell receptor (BCR) signalling; we noted that Dara significantly attenuated phosphorylated SYK, LYN, BTK, PLCγ2, ERK1/2, AKT, mTOR, and S6 levels, and this effect was augmented by cotreatment with ibrutinib. Indeed, WM cells, including ibrutinib-resistant WM cell lines treated with the ibrutinib + Dara combination, showed significantly more cell death through ADCC, CDC, ADCP and apoptosis relative to single-agent Dara or ibrutinib. In summary, we are the first to report the in vitro and in vivo anti-WM activity of Dara. Furthermore, we show a close connection between BCR and CD38 signalling, which can be co-targeted with ibrutinib + Dara to induce marked WM cell death, irrespective of acquired resistance to ibrutinib.

The Rate of Negative Appendicectomy and Perforated Appendicitis As Quality Indicators of the General Surgical Service in a District General Hospital in Cavan, Republic of Ireland.

Introduction Appendicitis is a common surgical condition that can be difficult to diagnose due to its varied clinical presentations. Surgical removal of the inflamed appendix is often necessary, and the appendix is sent for histopathological assessment to confirm the diagnosis. However, in some cases, the analysis may return a negative result for acute inflammation, known as a negative appendicectomy (NA). The definition of NA varies among experts. While negative appendicectomies are not ideal, they are accepted by surgeons to reduce the rate of perforated appendicitis, which can have severe consequences for patients. A study was conducted to investigate the rates of negative appendicectomies and their impact at a local district general hospital in Cavan, Republic of Ireland. Methods The study was conducted retrospectively from January 2014 to December 2019 on patients who were admitted with suspected appendicitis and underwent appendicectomy for appendicitis, regardless of age and sex. The researchers excluded patients who underwent elective, interval, and incidental appendicectomies. Data were collected on patient demographics, duration of symptoms prior to presentation, the intraoperative appearance of the appendix, and the histology results of the appendix specimens. Descriptive statistics and the Chi-squared test were used for data analysis with the help of IBM Statistical Package for the Social Sciences (SPSS) Version 26. Results The study retrospectively reviewed 876 patients who underwent an appendicectomy for suspected appendicitis between January 2014 and December 2019. The age distribution of patients was non-uniform, with 72% presenting before the third decade. The overall perforated appendicitis rate was 7.08%, and the overall negative appendicectomy (NA) rate was 21.3%. A subset analysis showed a statistically significant lower NA rate in females than in males. The NA rate decreased significantly over time and has been sustained since 2014 at around 10%, which is consistent with other published studies. The majority of the histology findings were uncomplicated appendicitis. Discussion This article discusses the challenges of diagnosing appendicitis and the need to reduce unnecessary surgeries. Laparoscopic appendectomy is the standard treatment, with an average cost of £2222.53 per patient in the UK. However, patients with negative appendicectomies (NA) have longer hospital stays and higher morbidity than uncomplicated cases, making it crucial to reduce unnecessary surgeries. The clinical diagnosis of appendicitis is not always straightforward, and the rate of perforated appendicitis increases with a longer duration of symptoms, particularly pain. The selective use of imaging in suspected appendicitis could reduce NA rates, but a statistical difference has not been proven. Scoring systems like the Alvarado score have limitations and cannot be relied upon alone. Retrospective studies have limitations, and biases and confounding variables must be considered. Conclusion The study found that a thorough investigation of patients, particularly with preoperative imaging, can decrease the rate of unnecessary appendectomies without increasing the rate of perforation. This could save costs and reduce harm to patients.

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.