Impact of Cardiovascular Diseases on in-Hospital Outcomes of CAR T-Cell Therapy in the United States

Introduction

With the expanding eligibility criteria for chimeric antigen receptor (CAR) T-cell therapy, there are more patients with diverse clinical characteristics receiving CAR T-cell therapy. However, data on the impact of pre-existing cardiovascular diseases (CVD) on patients receiving CAR T-cell therapy remains limited. Our study aimed to evaluate the impact of pre-existing CVD on the hospital outcomes among patients who received CAR T-cell therapy.

Methods

Using the Nationwide Readmissions Database (NRD), our study included patients aged ≥18 who received CAR T-cell therapy from 2018-2020. We compared the in-hospital outcomes between patients with and without pre-existing CVD. We used the sampling weights of the NRD dataset to produce national estimates. Univariable matched analysis was first performed. Patients’ variables, namely gender, age, and comorbidities including hypertension, diabetes, hyperlipidemia, cerebrovascular accident, vascular disease, pulmonary disease, anemia, obstructive sleep apnea, renal disease, and social factors such as smoking, alcohol use, and illicit drug use, were then included in a multivariable model for conditional logistic regression analyses. Analysis was performed using R studio software.

Results

After weighting, our study included 4,950 patients who received CAR T-cell therapy: 2,312 (46.7%) with pre-existing CVD and 2,638 (53.3%) without. Among patients with pre-existing CVD, 74.0% were diagnosed with non-Hodgkin lymphoma (NHL), 13.1% with multiple myeloma (MM), 2.8% with acute lymphocytic leukemia (ALL), and 10.0% with unspecified malignancy. Among patients without pre-existing CVD, 74.5% were diagnosed with NHL, 11.1% with MM, 5.9% with ALL, and 8.5% with unspecified malignancy. Although statistically insignificant, the prevalence of pre-existing CVD among patients who received CAR-T therapy increased from 38.5% in January-June 2018 to 47.6% in July-December 2020 (P=0.14). Patients with pre-existing CVD had significantly higher rates of in-hospital cardiovascular complications, including acute heart failure (2.9% vs. 0.7%; P=0.01) and acute myocardial infarction (2.2% vs. 0.9%; P<0.01) compared to patients without pre-existing CVD. There were also higher rates of cerebrovascular accident (1.4% vs. 0.7%; P<0.01) and acute kidney injury (19.2% vs. 13.3%; P<0.01) among those with pre-existing CVD than those without. Both groups had comparable rates of cardiogenic shock (0.3% vs. 0.2%; P=0.54), cardiac arrest (0.6% vs. 0.4%; P=0.39), and pulmonary embolism (1.1% vs. 0.8%; P=0.31). Through multivariate analysis, patients with pre-existing CVD were not associated with higher odds of early mortality (adjusted odd ratios [aOR]=1.01 [95% confidence intervals [CI], 0.69-1.49], p = 0.95), prolonged index hospitalization (aOR=0.94 [95% CI, 0.64-1.36], p = 0.73), non-home discharge (aOR 1.04 [95% CI, 0.79-1.38], p=0.77) and 30-day readmission (aOR 0.99 [95% CI, 0.81-1.20], p=0.91) compared to those without pre-existing CVD.

Conclusion

CAR T-cell therapy recipients with pre-existing CVD had higher rates of acute heart failure, myocardial infarction, cerebrovascular accident, and acute kidney injury than those without pre-existing CVD. These findings underscore the importance of increased vigilance among care providers in managing CAR T-cell therapy recipients with pre-existing CVD. Early consultation with a cardio-oncologist in managing these patients is crucial to improving outcomes among patients with pre-existing CVD.