Xie, Zhuoer

PURPOSE: The benefit of routine pre-emptive screening for severe acute respiratory syndrome coronavirus 2 infections in patients with cancer before cancer-directed therapies is unclear. Herein, we characterize the outcomes of a cohort of patients with cancer who were diagnosed with COVID-19 by routine screening (RS) in comparison with those diagnosed on the basis of clinical suspicion or exposure history (nonroutine screening [NRS]). METHODS: A multisite prospective observational study was conducted at three major and five satellite campuses of the Mayo Clinic Cancer Center between March 18 and July 31, 2020. The primary outcome was COVID-19–related hospital admission. Secondary outcomes included intensive care unit admissions and all-cause mortality. RESULTS: Five thousand four hundred fifty-two patients underwent RS in the outpatient setting only, and 44 (0.81%) were diagnosed with COVID-19. RS detected 19 additional patients from the scheduled inpatient admissions for surgical or interventional procedures or inpatient chemotherapy. One hundred sixty-one patients were diagnosed with COVID-19 on the basis of NRS. COVID-19–related hospitalization rate (17.5% v 26.7%; P = .14), intensive care unit admission (1.6% v 5.6%; P = .19), and mortality (4.8% v 3.7%; P = .72) were not significantly different between the RS and NRS groups. In the multivariable analysis, age ≥ 60 years (odds ratio, 4.4; P = .023) and an absolute lymphocyte count ≤ 1.4 × 109/L (odds ratio, 9.2; P = .002) were independent predictors of COVID-19–related hospital admission. CONCLUSION: The COVID-19 positivity rate was low on the basis of RS. Comparing the hospital admission and mortality outcomes with the NRS cohort, there were no significant differences. The value of routine pre-emptive screening of asymptomatic patients with cancer for COVID-19 remains low.

PURPOSE: The goal of this study was to assess the impact of an interdisciplinary remote patient monitoring (RPM) program on clinical outcomes and acute care utilization in cancer patients with COVID-19. METHODS: This is a cross-sectional analysis following a prospective observational study performed at Mayo Clinic Cancer Center. Adult patients receiving cancer-directed therapy or in recent remission on active surveillance with polymerase chain reaction–confirmed SARS-CoV-2 infection between March 18 and July 31, 2020, were included. RPM was composed of in-home technology to assess symptoms and physiologic data with centralized nursing and physician oversight. RESULTS: During the study timeframe, 224 patients with cancer were diagnosed with COVID-19. Of the 187 patients (83%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM. Following balancing of patient characteristics by inverse propensity score weighting, rates of hospitalization for RPM and non-RPM patients were 2.8% and 13%, respectively, implying that the use of RPM was associated with a 78% relative risk reduction in hospital admission rate (95% CI, 54 to 102; P = .002). Furthermore, when hospitalized, these patients experienced a shorter length of stay and fewer prolonged hospitalizations, intensive care unit admissions, and deaths, although these trends did not reach statistical significance. CONCLUSION: The use of RPM and a centralized virtual care team was associated with a reduction in hospital admission rate and lower overall acute care resource utilization among cancer patients with COVID-19.

Background Clonal cytopenia of undetermined significance (CCUS) is a newly described entity with a high probability to progress into myeloid disorders upon follow-up (Malcovati et al, Blood 2017). Little data is known on how to effectively treat patients with CCUS. We hereby describe a single institution experience in managing symptomatic CCUS patients. Methods Patients who had CCUS and underwent active treatment were identified after receiving IRB approval. CCUS diagnosis was rendered if patients had non-diagnostic bone marrow biopsy evaluation combined with evidence of pathogenic myeloid somatic mutation using our institution next generation sequencing (NGS) panel (OncoHeme, Mayo Clinic). "Symptomatic patients" is determined by patients who need therapy beyond blood transfusion. Treatment type is based on physicians' choice. Clinical and lab results were collected. Response and progression were graded based on the MDS IWG 2006 criteria. The date of treatment initiation was used for overall survival (OS) and progression (either to myeloid neoplasm or worsening cytopenias) free survival (PFS) calculation. Stata 14.1(StatCorp) was used for data analysis. Results 1) Cohort characteristics: Between 2015 and 2020, 24 patients met inclusion criteria with median age of 72 years (range: 24-87). Twenty (83%) were men. 15 (63%) were white, 1 (4%) African American, 1 (4%) Native American and 7 unknown (33%). Eighty percent had ECOG PS≤1. Four (17%) patients had prior other hematology disorders and 3 (13%) had solid tumor. Two (8%) patients had previous radiation therapy, 2 (8%) received chemotherapy and 1 (4%) received allogeneic stem cell transplantation. At the time of treatment, the median of hemoglobin was 8.9 (range 6.8-13.7) g/dL, white blood cell 2.9 (range 1.4-12.3) *109/L, and platelet 76 (range 8-407) *109/L. Red blood cell (RBC) and platelet transfusion dependency rate were 54% and 29%, respectively. We identified 23 different mutations. Most common mutations occurred in SRSF2 (N=5, 21%), TET2 (N=5, 21%), U2AF1 (N=5, 21%), and TP53 (N=4, 17%). Ten (42%) patients had 1 mutation, and 14 (58%) had ≥2 mutations. Treatment included hypomethylating agents (HMA) (N=10, 42%), growth factors (N=11, 46%), steroid (N=4, 17%), testosterone (N=2, 8%), cyclosporine (N=2, 8%), rituximab (N=1, 4%), immunoglobulin (N=1, 4%), vitamin B12 and iron (N=1, 4%). Seven (29%) patients received ≥2 treatments. Median follow up duration was 17.5 months (range 8.9-26.1). Median time from the diagnosis to treatment was 2.1 months (range 0-26.8). 2) Molecular correlation with response The overall response rate (RR) was 50% (hematological or symptomatic improvement). Most responders (67%) were treated with HMA (p=0.013). HMA treatment effect was not significantly associated with DNA methylation genes (DNMT3A, IDH1, IDH2 and TET2, all p>0.05). The RR was 100% for the three patients with IDH1 mutation (treated with HMA, steroid and erythropoietin stimulating agent (ESA), respectively). The RR was 100% for the 3 patients with ZRSR2 mutation (2 HMA, 1 testosterone). The RR was 0% for 3 patients with SF3B1 mutation (1 testosterone and ESA, 1 vitamin B12 and iron, and 1 HMA). The number of mutations had no impact on RR (p=0.41). Table demonstrates the RR for each treatment. 3) Survival and progression outcome At the last day of follow up, RBC and platelet transfusion dependency rate were 38% and 25%, respectively. The median PFS was 16.9 months (95% CI: 7.5-65.3). Six patients (25%) progressed to myeloid malignancy with 4 myelodysplastic syndrome (MDS) and 2 acute myeloid leukemia (AML). Five patients progressed with worsening cytopenias. Among the 4 MDS patients, they had SF3B1, TET2, and ASXL1 mutations at the diagnosis of CCUS. Within the 2 AML pts, 1 had RUNX1 mutation, 1 had BCOR, DNMT3A, PHF6, RUNX1, SF3B1, STAG2, and TET2 mutations at the diagnosis of CCUS. The median OS was not reached with an estimated 2 year OS 77%. Three (13%) patients progressed with cytopenia and died. Their NGS at CCUS diagnosis showed ASXL1, TP53 and U2AF1 mutations, respectively. Conclusion Patients with CCUS responded to available treatments used for myeloid diseases. HMA were effective in this cohort. Mutation profile may have an impact on treatment response. Studies of larger cohorts are needed to validate our findings. Additionally, development of response and progression criteria would be helpful for such patients for reporting treatment outcomes. Disclosures Shah: Dren Bio: Consultancy.

Abstract 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