Treatment patterns and outcomes of high-grade immune checkpoint inhibitor-related pneumonitis in an oncology hospitalist service.

PURPOSE: Immune checkpoint inhibitors (ICI) have become standard of care for some types of lung cancer. Along with expanding usage comes the emergence of immune-related adverse events (irAEs), including ICI-related pneumonitis (ICI-P). Treatment guidelines for managing irAEs have been developed; however, how clinicians manage irAEs in the real-world setting is less well known. We aimed to describe the outcomes and care patterns of grade ≥ 3 ICI-P in an onco-hospitalist service. PATIENTS AND METHODS: We included patients with lung cancer treated with ICI who were admitted to an oncology hospitalist service with a suspicion of ICI-P. We described the hospitalization characteristics, treatment patterns, discharge practices, and clinical outcomes of patients with confirmed ICI-P. The primary outcome was time to start treatment for ICI-P. RESULTS: Among 49 patients admitted with a suspicion of ICI-P, 31 patients were confirmed to have ICI-P and subsequently received ICI-P directed treatment. Pulmonology was consulted in 97% of patients. Median time to start treatment for ICI-P was 1 day (IQR 0-3.5 days). All 31 patients received corticosteroids. Inpatient mortality was 32%. Majority of patients discharged with steroids were prescribed prophylaxis for gastritis and opportunistic infections. Thirty-eight percent of patients were seen by pulmonology and 86% were seen by the oncology team post-discharge. CONCLUSION: Our study confirms prior findings of high mortality among patients with high-grade ICI-P. Early diagnosis and treatment are key to improving clinical outcomes. Understanding the care patterns and adherence to treatment guidelines of clinicians caring for this patient population may help identify ways to further standardize management practices and improve patient outcomes.

Cardiovascular Complications of Chimeric Antigen Receptor T-Cell Therapy: The Cytokine Release Syndrome and Associated Arrhythmias.

In recent years, cancer treatment has evolved, and new therapies have been introduced with significant improvement in prognosis. The immunotherapies stand out owing to their efficacy and remission rate. Chimeric antigen receptor (CAR) T-cell therapy is a part of this new era of therapies. Chimeric antigen receptor T-cell therapy is a form of adoptive cellular therapy that uses a genetically encoded CAR in modified human T cells to target specific tumor antigens in a nonconventional, non-major histocompatibility complex (MHC) protein presentation. Chimeric antigen receptor T-cell therapy successfully identifies tumor antigens and through activation of T cells destroys tumoral cells. It has been found to efficiently induce remission in patients who have been previously treated for B-cell malignancies and have persistent disease. As the use of this novel therapy increases, its potential side effects also have become more evident, including major complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokine release syndrome is a major systemic inflammatory process as a result of massive cytokine production by the proliferating and activated CAR T cells in which multiple interleukins and immune cells contribute to the inflammatory response. Cytokine release syndrome has been associated with cardiovascular life-threatening complications including hypotension, shock, tachycardia, arrhythmias, left ventricular dysfunction, heart failure, and cardiovascular death. Arrhythmias, among its major complications, vary from asymptomatic prolonged corrected QT interval (QTc) to supraventricular tachycardia, atrial fibrillation, flutter, and ventricular arrhythmias like Torsade de pointes. This article focuses on the cardiovascular complications and arrhythmias associated with CRS and CAR T-cell therapy.

Prognostic implications of relative hypochromia in ambulatory patients with chronic systolic heart failure.

Iron insufficiency has been associated with heart failure, but the impact of a reduction of hemoglobin content in the erythrocytes as estimated by mean corpuscular hemoglobin concentration (MCHC) to myocardial structure, performance, and long-term clinical outcomes has not been well-established. The authors examined hematologic data and long-term outcomes of 197 ambulatory patients with chronic systolic and symptomatic heart failure who underwent comprehensive echocardiographic evaluation. The authors observed that relative hypochromia (defined as low MCHC) was associated with higher natriuretic peptide levels (NT-proBNP, r =-0.40, P<.0001) and lower estimated glomerular filtration rate (eGFR; r = 0.45, P <. 0001) and correlated modestly with indices of left and right ventricular diastolic dysfunction (all P<.05), but were not related to left ventricular ejection fraction (LVEF, r=0.17, P=.079). After 5 years of follow-up, lower MCHC levels were associated with higher risk of death, transplant, or heart failure hospitalization after adjusting for age, LVEF, eGFR, and New York Heart Association class (hazard ratio, 1.34; 95% confidence interval, 1.04-1.72; P=.025), particularly in those with above-median hemoglobin (>13.8 g/dL; hazard ratio, 2.02; 95% confidence interval, 1.44-2.81, P<.0001). Taken together, the observations imply that physicians should take notice of the presence of relative hypochromia particularly in the absence of anemia in the setting of chronic systolic heart failure.

Pre-operative risk factors and clinical outcomes associated with vasoplegia in recipients of orthotopic heart transplantation in the contemporary era.

BACKGROUND: Patients who underwent orthotopic heart transplant (OHT) can develop vasoplegia, which is associated with high mortality and morbidity. Herein we examine the pre-operative risk in OHT recipients at our institution. METHODS: We reviewed peri-operative data from 311 consecutive adult patients who underwent OHT between January 2003 and June 2008. Vasoplegia was defined as persistent low systemic vascular resistance, despite multiple intravenous pressor drugs at high dose, between 6 and 48 hours after surgery. RESULTS: In our cohort of 311 patients, 35 (11%) patients developed vasoplegia syndrome; these patients were more likely to be UNOS Status 1A, with a higher body surface area (1.8 ± 0.25 vs 1.63 ± 0.36, p = 0.0007), greater history of thyroid disease (38.2% vs 18.5%, p = 0.0075) and a higher rate of previous cardiothoracic surgery (79% vs 48%, p = 0.0006). Pre-operatively, they were more frequently treated with aspirin (73% vs 48%, p = 0.005) and mechanical assist devices (ventricular assist devices [VADs]: 45% vs 17%, p < 0.0001; total artificial hearts: 8.6% vs 0%, p < 0.0001), and less treated with milrinone (14.7% vs 45.8%, p = 0.0005). Bypass time (118 ± 37 vs 142 ± 39 minutes, p = 0.0002) and donor heart ischemic time (191 ± 46 vs 219 ± 51 minutes, p = 0.002) were longer, with higher mortality (3.2% vs 17.1%, p = 0.0003) and morbidity in the first 30 days after transplant. In the multivariate analysis, history of thyroid disease (odds ratio [OR] = 2.7, 95% CI 1.0 to 7.0, p = 0.04) and VAD prior to transplant (OR = 2.8, 95% CI 1.07 to 7.4, p = 0.03) were independent risk factors for development of vasoplegia syndrome. CONCLUSIONS: High body mass index, long cardiopulmonary bypass time, prior cardiothoracic surgery, mechanical support, use of aspirin, and thyroid disease are risk factors associated with development of vasoplegia syndrome.