Management of Pericardial Effusion in Patients With Solid Tumor: An Algorithmic, Multidisciplinary Approach Results in Reduced Mortality After Paradoxical Hemodynamic Instability.

OBJECTIVE: This study compared outcomes in patients with solid tumor treated for pericardial effusion with surgical drainage versus interventional radiology (IR) percutaneous drainage and compared incidence of paradoxical hemodynamic instability (PHI) between cohorts. BACKGROUND: Patients with advanced-stage solid malignancies may develop large pericardial effusions requiring intervention. PHI is a fatal and underreported complication that occurs following pericardial effusion drainage. METHODS: Clinical characteristics and outcomes were compared between patients with solid tumors who underwent s urgical drainage or IR percutaneous drainage for pericardial effusion from 2010 to 2020. RESULTS: Among 447 patients, 243 were treated with surgical drainage, of which 27 (11%) developed PHI, compared with 7 of 204 patients (3%) who were treated with IR percutaneous drainage ( P =0.002); overall incidence of PHI decreased during the study period. Rates of reintervention (30-day: 1% vs 4%; 90-day: 4% vs 6%, P =0.7) and mortality (30-day: 21% vs 17%, P =0.3; 90-day: 39% vs 37%, P =0.7) were not different between patients treated with surgical drainage and IR percutaneous drainage. For both interventions, OS was shorter among patients with PHI than among patients without PHI (surgical drainage, median [95% confidence interval] OS, 0.89 mo [0.33-2.1] vs 6.5 mo [5.0-8.9], P <0.001; IR percutaneous drainage, 3.7 mo [0.23-6.8] vs 5.0 mo [4.0-8.1], P =0.044). CONCLUSIONS: With a coordinated multidisciplinary approach focusing on prompt clinical and echocardiographic evaluation, triage with bias toward IR percutaneous drainage than surgical drainage and postintervention intensive care resulted in lower incidence of PHI and improved outcomes.

Approaches for monitoring and treating cardiomyopathy among cancer survivors following anthracycline or thoracic radiation treatment.

BACKGROUND: Anthracycline chemotherapy and thoracic radiation therapy (RT) are known causes of cardiomyopathy among cancer survivors, however, management guidelines for this population are lacking. In this study we describe our single institution management approach for cancer survivors with low left ventricular ejection fraction (LVEF) secondary to cancer treatment. METHODS: We conducted a retrospective descriptive study of childhood and young adult (CAYA) cancer survivors in the Adult Long-Term Follow-Up Clinic at Memorial Sloan Kettering Cancer Center enrolled between November 2005 and July 2019. Those included were treated with anthracycline and/or thoracic RT as a part of their cancer therapy and had recorded a LVEF of < 55% on at least one post-treatment echocardiogram. Details regarding survivor characteristics, screening, and management were abstracted. Differences in management approaches among survivors with LVEF of 50-54.9%, 40-49.9%, and < 40% were described. Qualitative management approaches were abstracted as well. RESULTS: Among 668 CAYA survivors in the initial cohort, 80 were identified who had received anthracycline and/or thoracic RT and had a LVEF of < 55%. Median age at cancer diagnosis was 16.1 years, median time from cancer diagnosis was 25.8 years, and 55% of survivors were female. Cardiology referrals, nuclear stress tests, multi-gated acquisition scans, angiograms, echocardiograms, treatment with angiotensin converting enzyme inhibitors or receptor blockers, beta-blockers, diuretics, aldosterone antagonists, aspirin, and insertion of pacemaker or implantable cardioverter-defibrillators differed by LVEF category. Documentation suggested uncertainty regarding management of survivors with borderline low-LVEF, with low-LVEF that improved on follow-up, and with subsequent cancers requiring additional treatment. CONCLUSIONS: The management of CAYA cancer survivors with low-LVEF largely followed guidelines designed for the general population, however, uncertainty remains for issues specific to cancer survivors. Cardiomyopathy management guidelines that address issues specific to cancer survivors are needed.

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.

BACKGROUND: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs). OBJECTIVES: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy. METHODS: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR). RESULTS: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%. CONCLUSIONS: In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.

Prognostic Importance of Pretransplant Functional Capacity After Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: The purpose of this study was to investigate the prognostic importance of functional capacity in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for hematological malignancies. PATIENTS AND METHODS: Using a retrospective design, 407 patients completed a 6-minute walk distance (6 MWD) test to assess functional capacity before HCT; 193 (47%) completed a 6 MWD test after hospital discharge. Cox proportional hazards regression was used to estimate the risk of nonrelapse mortality (NRM) and overall survival (OS) according to the 6 MWD category (<400 m vs. ≥ 400 m) and the change in 6 MWD (before HCT to discharge) with or without adjustment for Karnofsky performance status (KPS), age, and other prognostic markers. RESULTS: Compared with <400 m, the unadjusted hazard ratio for NRM was 0.65 (95% confidence interval, 0.44-0.96) for a 6 MWD ≥ 400 m. A 6 MWD of ≥ 400 m provided incremental information on the prediction of NRM with adjustment for age (p = .032) but not KPS alone (p = .062) or adjustment for other prognostic markers (p = .099). A significant association was found between the 6 MWD and OS (p = .027). A 6 MWD of ≥ 400 m provided incremental information on the prediction of OS with adjustment for age (p = .032) but not for other prognostic markers (p > .05 for all). Patients presenting with a pre-HCT 6 MWD of <400 m and experiencing a decline in 6 MWD had the highest risk of NRM. CONCLUSION: The 6 MWD is a significant univariate predictor of clinical outcomes but did not provide prognostic information beyond that of traditional prognostic markers in HCT. IMPLICATIONS FOR PRACTICE: The pretransplant 6-minute walk test is a significant univariate predictor of clinical outcomes in hematological patients beyond age but not beyond that of performance status. On this basis, 6-minute walk distance testing should not be considered part of the standard battery of assessments for risk stratification before hematopoietic cell transplantation.

A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma.

Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is safe and effective in relapsed or refractory multiple myeloma (R/RMM). We report phase 2 results of carfilzomib 20 mg/m(2) on days 1 to 2 of cycle 1, 56 mg/m(2) thereafter (30-minute infusion), in R/RMM with the option of adding dexamethasone (20 mg) for suboptimal response/progression. Forty-four patients enrolled, all having prior bortezomib and immunomodulatory drugs and a median of 5 prior regimens. Of 42 response-evaluable patients, 23 (55%) achieved at least partial response (PR). Median (95% confidence interval) duration of response, progression-free, and overall survival were 11.7 (6.7-14.7), 4.1 (2.5-11.8), and 20.3 months (6.4-not estimable), respectively. High-risk cytogenetics did not impact outcomes. Treatment was active in bortezomib-refractory subgroups, but these patients tended to have poorer outcomes. Four/10 patients with prior allogeneic transplant achieved at least PR. Of 6 patients who responded, progressed and had dexamethasone added, 4 achieved at least stable disease. The most frequent grade 3/4 adverse events (AEs) possibly related to carfilzomib included lymphopenia (43%), thrombocytopenia (32%), hypertension (25%), pneumonia (18%), and heart failure (11%). Seven patients (16%) discontinued treatment due to AEs. Carfilzomib 56 mg/m(2) ± dexamethasone was tolerable and provided durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01351623.

Late cardiovascular toxicity following chemotherapy for germ cell tumors.

The introduction of cisplatin-based chemotherapy has transformed germ cell tumors (GCTs), the most common malignancy to affect young adult men, into a highly curable cancer, even in the setting of advanced disease. However, over the past decade, the success of these chemotherapy regimens in curing GCTs has been temporized by an increasing recognition of their important late toxicities, such as cardiovascular disease. The relative risk of coronary artery disease in this population is particularly elevated within the first 10 years of follow-up, when patients are still in their 30s and 40s, which are age groups often considered too young to experience cardiovascular events. Two hypotheses have been proposed to explain the association between chemotherapy and cardiovascular disease in this population. The direct hypothesis asserts that chemotherapy causes diffuse endothelial damage, including in the coronary arteries, gradually leading to cardiovascular disease. In contrast, the indirect hypothesis proposes that chemotherapy leads to an increased incidence of cardiovascular disease risk factors, such as hypertension, hyperlipidemia, and the metabolic syndrome, which in turn enhance the risk of cardiovascular disease. This article summarizes the data on the association between chemotherapy (predominantly cisplatin-based) and the development of cardiovascular disease among GCT survivors, and reviews the evidence supporting both mechanistic hypotheses. In addition, recommendations are provided for the management of GCT survivors who received cisplatin-based chemotherapy and are therefore at risk for cardiovascular toxicity.

Retrospective outcome data for hematopoietic stem cell transplantation in patients with concurrent coronary artery disease.

Hematopoietic stem cell transplantation (HSCT) represents an extended period of physiologic stress. It is unknown whether patients with pre-existing coronary artery disease (CAD) may be poor transplant candidates. There are no data analyzing the risk of transplantation in this population. Sixty-nine patients with CAD who underwent 72 transplantations, autologous and allogeneic, were identified retrospectively. Fifty-five percent of these patients had prior percutaneous coronary intervention, 42% had verifiable history of myocardial infarction, and 23% had prior coronary artery bypass grafting. Outcomes were compared to 1109 patients without established CAD who underwent 1183 transplants during the same time period. Cancer diagnoses in the 2 groups were similar, predominantly lymphoma, multiple myeloma, and leukemia. There was no significant difference between the CAD group and the control group with respect to type of transplant (autologous 68% versus 64%, P = .612, myeloablative 86% versus 85%, P = .867). Treatment-related mortality was no different in the CAD group versus the control group (5.6% versus 4.9%, P = .777), nor were there differences in mortality at 1 year (15.3% versus 16.6%, P = .871), urgent intensive care unit admission (11.1% versus 9.9%, P = .686), or length of stay (25.5 days versus 28.4 days, P = .195). These findings suggest many patients with underlying coronary artery disease may be safely managed through hematopoietic stem cell transplantation.