Cardiovascular Effects of CAR T Cell Therapy: A Retrospective Study

Abstract

Background: Anti-CD19 chimeric antigen receptor (CAR) T cell (CART19) therapy holds great promise in the treatment of hematological malignancies. A high occurrence of cardiac dysfunction has been noted in children treated with CART19 therapy.

Objectives: We aimed to define the occurrence of major cardiovascular events (MACE) in adult patients treated with CART19 cells and assess the relationships between clinical factors, echocardiographic parameters, laboratory values, and cardiovascular outcomes.

Methods: Baseline clinical, laboratory and echocardiographic parameters were collected in 145 adult patients undergoing CART19 cell therapy. MACE included cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke and de novo cardiac arrhythmia. Baseline parameters associated with MACE were identified using Cox proportional cause-specific hazards regression analysis.

Results: Thirty-one patients had MACE (41 events) at a median time of 11 days (Q1-Q3:6-151 days) after CART19 cell infusion. The median follow-up period was 456 days (Q1-Q3: 128-1214 days). Sixty-one patients died. Cytokine release syndrome (CRS) occurred 176 times in 104 patients; the median time to CRS was 6 days (Q1-Q3: 1-8 days). The Kaplan-Meier estimates for MACE and CRS at 30 days were 17% and 53% respectively. The KM estimates for survival at 1 year was 71%. Multivariable Cox proportional cause-specific hazards regression analysis determined that baseline creatinine and Grade 3 or 4 CRS were independently associated with MACE.

Conclusion: Patients treated with CART19 are at an increased risk of MACE and may benefit from cardiovascular surveillance. Further large prospective studies are needed to confirm the incidence and risk factors predictive of MACE.

Keywords: CART cells; Cardio-oncology; Cardiovascular.

Graphical abstract

Figure 1

Kaplan-Meier Estimates of CRS (Left) Kaplan-Meier curve at 30 days. (Right) Kaplan-Meier curve over 360 days. The Kaplan-Meier estimates for cytokine release syndrome (CRS) were 53% at 30 days, 64% at 6 months, and 71% at 12 months.

Figure 2

Kaplan-Meier Estimates of Survival Rate The Kaplan-Meier estimates for survival were 95% at 30 days, 81% at 6 months, and 71% at 12 months.

Figure 3

Kaplan-Meier Estimates of MACE (Left) Kaplan-Meier curve at 30 days. (Right) Kaplan-Meier curve over 360 days. The Kaplan-Meier estimates for major adverse cardiovascular events (MACE) were 17% at 30 days, 19% at 6 months, and 21% at 12 months.

Central Illustration

Timeline Demonstrating the Relationship Among Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Infusion, Cytokine Release Syndrome, and Major Adverse Cardiovascular Events As the median time to major adverse cardiovascular events (MACE) was 5 days later than the median time to cytokine release syndrome (CRS) onset, this suggests that CRS and its treatments can at least contribute to the occurrence of MACE in patients treated with anti-CD19 chimeric antigen receptor T cell therapy. IQR = interquartile range (25th to 75th quartile).