To determine the incidence and complications of myelodysplastic syndromes (MDS) among Medicare beneficiaries.
Retrospective review of 2003 Medicare Standard Analytic Files utilizing International ...Classification of Diseases for Oncology ninth edition CM code 238.7 to identify new MDS patients, with 3-year follow-up.
Among 1,394,343 individuals in Medicare Standard Analytic Files age > or = 65 years, 162 per 100,000 were coded as newly diagnosed MDS during 2003 yielding a calculated 45,000 new cases in the United States Medicare > or = 65 years population. Patients with MDS were older (median age, 77 years), and over-represented by males. Among patients with MDS diagnosed during first quarter of 2003, 73.2% suffered cardiac-related events during 3-year follow-up, which exceeded the Medicare population (54.5%; P < .01) even when age adjusted (odds ratio, 2.10; P < .01). Significant increases in prevalence of diabetes (40.0% v 33.1%), dyspnea (49.4% v 28.5%), hepatic diseases (0.8% v 0.2%), and infections (sepsis: 22.5% v 6.1%) were noted in MDS (all P < .01) compared with the Medicare population. Patients with MDS requiring RBC transfusions had greater prevalence of these comorbidities. Acute myeloid leukemia developed within 3 years in 9.6%, with increased transformation among transfused (24.6%; P < .001). The 3-year Kaplan-Meier age-adjusted survival for MDS was 60.0%, which was significantly lower than the Medicare population (84.7%; hazard ratio, 3.08; P < .001), and mortality was further increased among transfused MDS (P < .01). In 2003, median payment for MDS was $16,181, compared to $1,575 for the Medicare population (P < .001).
MDS is a common hematologic malignancy of the elderly, which places patients at risk for comorbid conditions. Transfusion dependency identifies patients with MDS at additional increased risk of organ impairment and shortened survival.
Abstract Background National guidelines advocate broad molecular profiling as part of the standard diagnostic evaluation for advanced non-small cell lung cancer (NSCLC), with the goal of identifying ...driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines may present challenges to community oncologists. Methods Retrospective review of genomic testing patterns in patients with non-squamous NSCLC treated by 89 oncologists at 15 sites throughout New Jersey and Maryland between January 2013 and December 2015. Results 814 patients (89% stage IV; 11% stage IIIB) were identified in the COTA database. 479 (59%) met guideline recommendations for EGFR and ALK biomarker testing; 63 (8%) underwent comprehensive genomic profiling (CGP) for all four major types of alterations (point mutations, indels, fusions and copy number amplifications). Gender, age, race, site of care (referral vs. community center), and practice size did not influence CGP frequency. Active smokers and patients who died within 30 days were tested less frequently (p<0.05). Among those not tested for EGFR and ALK , 52% received chemotherapy without documented reasons for non-testing, 32% did not receive anti-neoplastic therapy and 13% had insufficient tissue for genotyping. Conclusions Genomic testing presents multiple logistical challenges for the community based oncologist, including coordination of sample handling, long turnaround times, test reimbursement, access to targeted therapies, insufficient tissue, and the patient harm from repeat biopsies necessary if tissue is insufficient. Opportunities exist for improvement in guideline adherence, possibly through new technologies such as “liquid biopsies,” which obviate tissue biopsy in select settings.
Objectives The development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health ...preparations. Methods We retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset. Results The study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate greater than or equal to25/minute upon hospital presentation, oxygenation <94% on hospital presentation, and pre-hospital comorbidities of hypertension, coronary artery disease, or chronic renal disease. The risk score was highly prognostic of mortality in a training set and confirmatory set yielding in the combined dataset a hazard ratio of 1.80 (95% CI, 1.72, 1.87) for one unit increases. Using observed mortality within 20 equally sized bins of risk scores, a predictive model for an individual's 40-day risk of mortality was generated as -14.258 + 13.460*RS + 1.585*(RS-2.524)^2-0.403*(RS-2.524)^3. An online calculator of this 40-day COVID-19 mortality risk score is available at www.HackensackMeridianHealth.org/CovidRS. Conclusions A risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19. Trial registration Clinicaltrials.gov Identifier: NCT04347993.
Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective ...observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 95% CI, 0.80-1.22), hydroxychloroquine alone (HR, 1.02 95% CI, 0.83-1.27), or hydroxychloroquine with azithromycin (HR, 0.98 95% CI, 0.75-1.28). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 95% CI, 0.57-1.00), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.
Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with
-mutant metastatic ...melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy.
In a phase III trial, patients with treatment-naive
-mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety.
A total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank
= .010). Step 1 progression-free survival favored arm A (
= .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B (
< .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated.
Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.
Background The objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow–derived CD34+ cells after ST elevation myocardial ...infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells. Methods Patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34+ cells were infused via the IRA at 3 dose levels (5, 10, and 15 × 106 ) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34+ cell mobility were performed. Results Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥10 million cohorts compared with controls (−256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the ≥10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34+ cells. Conclusions The effects of CD34+ cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34+ cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34+ cells in patients with acute myocardial infarction AMR-01 NCT00313339).
Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective ...prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting.
We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching.
Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available.
In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.
Summary
Relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months ...of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first‐relapse or primary refractory DLBCL. Dose‐escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM BCNU (carmustine), etoposide, cytarabine, melphalan followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose‐limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high‐risk DLBCL patients.
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