Faculty Bibliography

Importance/UNASSIGNED:Recently, the benefit of adding daratumumab to the proteasome inhibitor-based, 3-drug combination of bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed multiple myeloma who underwent high-dose melphalan chemotherapy and autologous hemopoietic cell transplant was assessed. Here, we examine the addition of daratumumab to the second-generation proteasome inhibitor-based, 3-drug combination of carfilzomib, lenalidomide, and dexamethasone. Objective/UNASSIGNED:To assess the safety and effectiveness of carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy for patients with newly diagnosed multiple myeloma, in the absence of high-dose melphalan chemotherapy and autologous hemopoietic cell transplant. Design, Setting, and Participants/UNASSIGNED:Clinical and correlative pilot study at the Memorial Sloan Kettering Cancer Center in New York, New York. Patients with newly diagnosed multiple myeloma were enrolled between October 1, 2018, and November 15, 2019. The median follow-up from start of treatment was 20.3 months (95% CI, 19.2-21.9 months). Interventions/UNASSIGNED:Eight 28-day cycles with intravenous carfilzomib, 20/56 mg/m2 (days 1, 8, and 15); oral lenalidomide, 25 mg, (days 1-21); dexamethasone, 40 mg weekly, orally or intravenously (cycles 1-4), and 20 mg after cycle 4; and intravenous daratumumab, 16 mg/kg (days 1, 8, 15, and 22 [cycles 1-2]; days 1 and 15 [cycles 3-6]; and day 1 [cycles 7 and 8]). Main Outcomes and Measures/UNASSIGNED:The primary end point was the minimal residual disease (MRD) rate, in the absence of high-dose melphalan chemotherapy and autologous hemopoietic cell transplant. Secondary end points included determining safety and tolerability, evaluating rates of clinical response per the International Myeloma Working Group, and estimating progression-free survival (PFS) and overall survival (OS) rates. Results/UNASSIGNED:Forty-one evaluable patients were enrolled (median age, 59 years; range, 30-70 years); 25 (61%) were female, and 20 (49%) had high-risk multiple myeloma. The primary end point (MRD negativity in the bone marrow; 10-5 sensitivity) was achieved in 29 of 41 patients (71%; 95% CI, 54%-83%), and therefore the trial was deemed successful. Median time to MRD negativity was 6 cycles (range, 1-8 cycles). Secondary end points of the overall response rate and the very good partial response or complete response rate were 100% (41 of 41 patients) and 95% (39 of 41 patients), respectively. At 11 months of the median follow-up, the 1-year PFS rate and the OS rate were 98% (95% CI, 93%-100%) and 100%, respectively. Most common (≥2 patients) grade 3 or 4 adverse events were neutropenia (12 patients [27%]), rash (4 patients [9%]), lung infection (3 patients [7%]), and increased alanine aminotransferase level (2 patients [4%]). There were no deaths. Conclusions and Relevance/UNASSIGNED:In this nonrandomized clinical trial, carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy was associated with high rates of MRD negativity in patients with newly diagnosed multiple myeloma and high rates of PFS.

OBJECTIVE:The aim of the study was to determine the main factors contributing to hospital readmissions and their potential preventability after a coronavirus disease 2019 (COVID-19) hospitalization at 2 New York City hospitals. METHODS:This was a retrospective study at 2 affiliated New York City hospitals located in the Upper East Side and Lower Manhattan neighborhoods. We performed case reviews using the Hospital Medicine Reengineering Network framework to determine potentially preventable readmissions among patients hospitalized for COVID-19 between March 3, 2020 (date of first case) and April 27, 2020, and readmitted to either of the 2 hospitals within 30 days of discharge. RESULTS:Among 53 readmissions after hospitalization for COVID-19, 44 (83%) were deemed not preventable and 9 (17%) were potentially preventable. Nonpreventable readmissions were mostly due to disease progression or complications of COVID-19 (37/44, 84%). Main factors contributing to potentially preventable readmissions were issues with initial disposition (5/9, 56%), premature discharge (3/9, 33%), and inappropriate readmission (1/9, 11%) for someone who likely did not require rehospitalization. CONCLUSIONS:Most readmissions after a COVID-19 hospitalization were not preventable and a consequence of the natural progression of the disease, specifically worsening dyspnea or hypoxemia. Some readmissions were potentially preventable, mostly because of issues with disposition that were directly related to challenges posed by the ongoing COVID-19 pandemic. Clinicians should be aware of challenges with disposition related to circumstances of the COVID-19 pandemic.

Thoracic aortic calcium(TAC) is an important marker of extracoronary atherosclerosis with established predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium (CAC) score. The CAC Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no previous history of cardiovascular disease, baseline CAC scans for risk stratification, and follow-up for 12 ± 4 years. CAC scans capture the adjacent thoracic aorta, enabling assessment of TAC from the same images. TAC was available in 41,066 (62%), and was primarily analyzed as present or not present. To account for competing risks for nonstroke death, we utilized multivariable-adjusted Fine and Gray competing risk regression models adjusted for traditional cardiovascular risk factors and CAC score. The mean age of participants was 53.8 ± 10.3 years, with 34.4% female. There were 110 stroke deaths during follow-up. The unadjusted subdistribution hazard ratio (SHR) for stroke mortality in those who had TAC present compared with those who did not was 8.80 (95% confidence interval [CI]: 5.97, 12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21 (95% CI:1.39,3.49). In sex-stratified analyses, the fully adjusted SHR for females was 3.42 (95% CI: 1.74, 6.73) while for males it was 1.55 (95% CI: 0.83, 2.90). TAC was associated with stroke mortality independent of CAC and traditional risk factors, more so in women. The presence of TAC appears to be an independent risk marker for stroke mortality.