Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma.

Although Janus kinase (JAK) inhibitors have demonstrated efficacy for treating autoimmune disorders and myeloproliferative neoplasms, their efficacy in treating other types of cancer has not been clearly demonstrated. We evaluated oral ruxolitinib (15 mg twice daily) with oral methylprednisolone (40 mg every other day) for multiple myeloma (MM) patients with progressive disease who had received a proteasome inhibitor, lenalidomide, glucocorticosteroids and three or more prior regimens. All of the planned 29 patients had been enrolled with follow-up until 28 April 2022. Median lines of prior therapy were 6 (range 3-12). Cytogenetics and fluorescent in situ hybridization were evaluable in 28 patients; 9 (32%) and 17 (70%) patients showed high-risk cytogenetics and/or 1q+, respectively. The overall response rate was 31%. The median duration of response was 13.1 (range 2.8-22.0) months. Median progression-free survival rate was 3.4 (range 0.5-24.6) months, Overall, the treatment was well tolerated. The combination of ruxolitinib and methylprednisolone demonstrated significant clinical activity among previously heavily-treated MM patients, and responses were achieved among patients who had high-risk cytogenetics. This is the first clinical study to show activity of JAK inhibitors in combination with steroids for MM patients and expands the potential use of these drugs to those with cancers other than myeloproliferative neoplasms.

Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study.

BACKGROUND: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19. METHODS: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed. RESULTS: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity. CONCLUSIONS: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

Use of synchronous kidney and lung extracorporeal support for severe COVID-19: A single-center retrospective study.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus disease 2019 (COVID-19) has been associated with both kidney and respiratory failure. During the early phase of the coronavirus disease pandemic, patients often required the use of mechanical assistance to provide adequate kidney and lung function. In this paper we describe the clinical outcomes of patients who required synchronous kidney and lung extracorporeal support for COVID-19. MATERIALS AND METHODS: All patients admitted to Baylor University Medical Center, Dallas, between February 1, 2020, to April 23, 2021, with COVID-19 who required both extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were retrospectively analyzed. Patients who were on hemo- or peritoneal dialysis prior to admission or who required veno-arterial (VA) ECMO were excluded. RESULTS: 35 patients with COVID-19 required ECMO and CRRT support. Four patients (11%) were excluded, 2 due to being on dialysis prior to admission and 2 due to the requirement of VA-ECMO. The median time on CRRT was 33 days (IQR 13 - 51). The median time on ECMO was 28 days (IQR 10.5 - 59.5). At 90 days, 9 patients had died (29%), 4 patients remained hospitalized, and 18 patients had been discharged: 10 to long-term acute care, 2 to inpatient rehabilitation, and 6 to home. CONCLUSION: Patients with severe COVID-19 requiring concurrent ECMO and CRRT in this institution had a 29% mortality at 90 days.

Extracorporeal membrane oxygenation for respiratory failure in phases of COVID-19 variants.

BACKGROUND: Adaptive mutations of the severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) virus have emerged throughout the coronavirus disease 2019 (COVID-19) pandemic. The characterization of outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory distress from COVID-19 during the peak prevalence of different variants is not well known. METHODS: There were 131 patients with laboratory-confirmed SARS-CoV-2 infection supported by ECMO at two referral centers within a large healthcare system. Three predominant variant phase time windows (Pre-Alpha, Alpha, and Delta) were determined by a change-point analyzer based on random population sampling and viral genome sequencing. Patient demographics and outcomes were compared. RESULTS: The average age of patients was 46.9 ± 10.5 years and 70.2% (92/131) were male. Patients cannulated for ECMO during the Delta variant wave were younger compared to earlier Pre-Alpha (39.3 ± 7.8 vs. 48.0 ± 11.1 years) and Alpha phases (39.3 ± 7.8 vs. 47.2 ± 7.7 years) (p < .01). The predominantly affected race in the Pre-Alpha phase was Hispanic (52.2%; 47/90), while in Alpha (61.5%; 16/26) and Delta (40%; 6/15) variant waves, most patients were White (p < .01). Most patients received a tracheostomy (82.4%; 108/131) with a trend toward early intervention in later phases compared to Pre-Alpha (p < .01). There was no significant difference between the duration of ECMO, mechanical support, intensive care unit (ICU) length of stay (LOS), or hospital LOS over the three variant phases. The in-hospital mortality was overall 41.5% (54/131) and was also similar. Six-month survival of patients who survived to discharge was 92.2% (71/77). CONCLUSIONS: There was no significant difference in survival or time on ECMO support in patients during the peak prevalence of the three variants.

Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients.

Treatment of acute respiratory distress syndrome from COVID-19 with extracorporeal membrane oxygenation in obstetrical patients.

BACKGROUND: Extracorporeal membrane oxygenation therapy has been used as a rescue therapy for patients with severe acute respiratory distress syndrome from COVID-19 who have failed conventional ventilatory strategies. Little is known about the outcome of pregnant and postpartum patients on extracorporeal membrane oxygenation therapy. OBJECTIVE: To describe the medical and surgical outcomes of pregnant and postpartum patients who were placed on extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome from COVID-19. STUDY DESIGN: A case series reviewing pregnant or postpartum patients with laboratory-confirmed COVID-19 who were placed on extracorporeal membrane oxygenation therapy was conducted within the Baylor Scott & White Healthcare system. The demographics and the medical and surgical outcomes were collected and reviewed. RESULTS: Between March 2020 and October 2021, 5 pregnant and 5 postpartum women were supported with venovenous extracorporeal membrane oxygenation therapy. The median age was 30 years (interquartile range, 26-33.5) and the median body mass index was 36.6 kg/m2 (interquartile range, 29.5-42.0). There was a median of 4.5 days (interquartile range, 1.5-6.8) from admission to any hospital to intubation and 9 days (interquartile range, 7-13) to extracorporeal membrane oxygenation therapy cannulation. One patient had an ischemic stroke, 1 patient had a presumed hemorrhagic stroke, and 9 patients developed bleeding while on extracorporeal membrane oxygenation therapy. Of the 5 pregnant women, 2 patients had intrauterine fetal demise and 3 underwent delivery for maternal hemodynamic instability. The 5 postpartum women were initiated on extracorporeal membrane oxygenation therapy a median of 10 days (interquartile range, 3-11) after delivery. The median length of time on extracorporeal membrane oxygenation therapy was 22 days (interquartile range, 11-31). At the time of the study, there were 2 inpatient mortalities, 6 patients survived to discharge from the extracorporeal membrane oxygenation therapy hospital, and 2 patients were still admitted. CONCLUSION: There is limited information regarding the use of extracorporeal membrane oxygenation therapy for COVID-19 acute respiratory distress syndrome in obstetrical patients. This case series describes the use of extracorporeal membrane oxygenation therapy and survival in pregnant and postpartum patients with COVID-19.

Outcomes of Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Distress Syndrome Caused by COVID-19 Versus Influenza.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be effective for refractory acute respiratory distress syndrome (ARDS) in patients with influenza, but its utility in patients with coronavirus disease 2019 (COVID-19) is uncertain. We compared outcomes of patients with refractory ARDS from COVID-19 and influenza placed on ECMO. METHODS: We conducted a retrospective analysis of 120 patients with refractory ARDS due to COVID-19 or influenza placed on ECMO at 2 referral centers from January 2013 to October 2020. Patient characteristics and clinical outcomes were compared. The primary endpoint was survival to discharge. RESULTS: Baseline characteristics and comorbidities were similar. During the study period, 53 patients with COVID-19 and 67 patients with influenza were supported. Venovenous ECMO was the predominant initial cannulation strategy in both groups (COVID 92.5% vs influenza 95.5%; P = .5). Survival to hospital discharge was 62.3% (33 of 53 patients) in the COVID-19 group and 64.2% (43 of 67 patients) in the influenza group (P = .8). In patients successfully decannulated, median length of time on ECMO was longer in COVID-19 patients (14 [interquartile range (IQR), 9-30] days vs influenza 10.5 [IQR, 6.8-14.3] days; P = .004). Among patients discharged alive, COVID-19 patients had longer overall length of stay (COVID-19 37 [IQR, 27-62] days vs influenza 13.5 [IQR, 9.3-24] days; P = .007). CONCLUSIONS: In patients with refractory ARDS from COVID-19 or influenza placed on ECMO, there was no significant difference in survival to hospital discharge. In patients surviving to decannulation, the duration of ECMO support and total length of stay were longer in COVID-19 patients.

Characteristics and outcomes of patients with COVID-19 supported by extracorporeal membrane oxygenation: A retrospective multicenter study.

OBJECTIVE: To determine characteristics, outcomes, and clinical factors associated with death in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support. METHODS: A multicenter, retrospective cohort study was conducted. The cohort consisted of adult patients (18 years of age and older) requiring ECMO in the period from March 1, 2020, to September 30, 2020. The primary outcome was in-hospital mortality after ECMO initiation assessed with a time to event analysis at 90 days. Multivariable Cox proportional regression was used to determine factors associated with in-hospital mortality. RESULTS: Overall, 292 patients from 17 centers comprised the study cohort. Patients were 49 (interquartile range, 39-57) years old and 81 (28%) were female. At the end of the follow-up period, 19 (6%) patients were still receiving ECMO, 25 (9%) were discontinued from ECMO but remained hospitalized, 135 (46%) were discharged or transferred alive, and 113 (39%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%). Factors associated with in-hospital mortality were age (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.06-1.61 per 10 years), renal dysfunction measured according to serum creatinine level (aHR, 1.21; 95% CI, 1.01-1.45), and cardiopulmonary resuscitation before ECMO placement (aHR, 1.87; 95% CI, 1.01-3.46). CONCLUSIONS: In patients with severe COVID-19 necessitating ECMO support, in-hospital mortality occurred in fewer than half of the cases. ECMO might serve as a viable modality for terminally ill patients with refractory COVID-19.

Venovenous extracorporeal membrane oxygenation for patients with refractory coronavirus disease 2019 (COVID-19): Multicenter experience of referral hospitals in a large health care system.

BACKGROUND: The benefit of extracorporeal membrane oxygenation (ECMO) for patients with severe acute respiratory distress from coronavirus disease 2019 refractory to medical management and lung-protective mechanical ventilation has not been adequately determined. METHODS: We reviewed the clinical course of 37 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection supported by venovenous ECMO at 4 ECMO referral centers within a large health care system. Patient characteristics, progression of hemodynamics and inflammatory markers, and clinical outcomes were evaluated. RESULTS: The patients had median age of 51 years (interquartile range, 40-59), and 73% were male. Peak plateau pressures, vasopressor requirements, and arterial partial pressure of carbon dioxide all improved with ECMO support. In our patient population, 24 of 37 patients (64.8%) survived to decannulation and 21 of 37 patients (56.8%) survived to discharge. Among patients discharged alive from the ECMO facility, 12 patients were discharged to a long-term acute care or rehabilitation facility, 2 were transferred back to the referring hospital for ventilatory weaning, and 7 were discharged directly home. For patients who were successfully decannulated, median length of time on ECMO was 17 days (interquartile range, 10-33.5). CONCLUSIONS: Venovenous ECMO represents a useful therapy for patients with refractory severe acute respiratory distress syndrome from coronavirus disease 2019.

Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426.

A double-edged sword: Prolonged detection of SARS-COV-2 in patients receiving cancer directed therapy.

INTRODUCTION: SARS-CoV-2 (S-2) infection duration and its impact on patients with cancer and mild to moderate COVID-19 undergoing cancer-directed therapy (CDT), especially in the underserved population, is not well described. We conducted a retrospective study to analyze S-2 positive (+) patients on CDT to describe the S-2 duration and its impact on CDT. METHODS: Two hundred ninety-nine patients with cancer were tested with nasopharyngeal (NP) S-2 PCR assay at Columbia University Medical Irving Center (CUIMC), a Minority-NCI Community Oncology site, of which 77 (26%) tested positive. We retrospectively analyzed 26 S-2 (+) patients with mild-to-moderate COVID-19 receiving CDT who consented to the study. NP PCR was repeated every 1 to 2 weeks until 2 successive negative (-) PCRs were obtained prior to restarting CDT. Time to 2 (-) PCR and serology results were recorded. Cycling thresholds (Ct) were obtained for S-2 specific targets and represented an indirect measure of viral load. RESULTS: Demographics of N = 26 patients are: Hispanic (N = 17, 65%), Black (N = 1, 4%), White (N = 7, 27%), and undeclared (N = 1, 4%). Among the tumor histologies represented, gastrointestinal (N = 9, 35%), breast (N = 5, 19%), and sarcoma (N = 3, 12%) were most common. Median time to 2 (-) PCR was 32 days. Twenty patients required greater than 14 days to achieve 2 sequential (-) swabs. CDT was delayed in 21 patients (81%) of whom three experienced disease progression, likely attributed to an interruption in CDT, which was delayed by a mean of 53 days. Interestingly, nine (41%) patients had Ct values greater than 34 for the pan SARS target and seven (32%) patients had Ct values greater than 34 for the SARS-COV-2 target. Sixteen of 16 patients on CDT, tested positive for IgG antibodies at the time of consent, despite protracted viral detectability by NP PCR. CONCLUSION: Patients receiving CDT appear to have prolonged detectable S-2 by PCR, which can lead to interruption of CDT and POD in patients. We believe and recommend that patients with asymptomatic to mild COVID-19 and aggressive malignancies are at greatest risk for cancer related morbidity and mortality due to CDT cessation and should be considered for continued CDT without interruption. Ct values and serology testing are tools that can help identify those patients on CDT who may be at greatest risk of worsening COVID-19 or of spreading S-2.

Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020.

PURPOSE: This ecological analysis investigates the spatial patterns of the COVID-19 epidemic in the United States in relation to socioeconomic variables that characterize US counties. METHODS: Data on confirmed cases and deaths from COVID-19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state-level measure of the percent of the population that has been tested for COVID-19 was used to control for the impact of testing. FINDINGS: The impact of COVID-19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID-19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested. CONCLUSIONS: Knowledge about the spatial aspects of the COVID-19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to "shelter-in-place" should continue to stem the spread of COVID-19.