Impact of tumor lysis syndrome on clinical outcomes and healthcare burden in chimeric antigen receptor T-cell therapy patients: Key insights from United States population data.

Abstract

e19000 Background: Tumor lysis syndrome (TLS) is a known complication of hematologic malignancy treatments, often leading to fatal arrhythmias, acute kidney injury, and seizures. Chimeric Antigen Receptor T-cell (CAR-T) therapy, used for relapsed or refractory non-Hodgkin's lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and multiple myeloma (MM), has been increasingly associated with TLS. Single-center studies suggest that TLS in CAR-T patients correlates with lower overall survival, but its population-level impact remains underexplored. This study evaluates the effect of TLS on in-hospital outcomes in CAR-T patients using United States population data. Methods: We used the National Inpatient Sample to identify adult patients with ALL, NHL, and MM who underwent CAR-T between 2018 and 2021, based on ICD-10 codes. The cohort was stratified by TLS presence, with complex sampling weights used for national representation. We compared socio-demographic characteristics and comorbidities between groups. The primary outcome was all-cause mortality, with secondary outcomes assessed. Multivariate regression models evaluated outcome disparities, with significance set at p < 0.05. Results: We identified 4,120 adults who received CAR-T between 2018 and 2021 (82.5% NHL, 12.6% MM, 4.9% ALL), of whom 260 (6.3%) had concurrent TLS. A higher proportion of TLS patients had Medicare coverage (42.3% vs. 39.4%, p < 0.05), with no other significant demographic differences. The overall mortality rate was 3.0%, compared to 17.3% in the TLS group. TLS was associated with higher odds of all-cause mortality (adjusted odds ratio [aOR] 8.5, 95% CI 3.5–20.5), respiratory failure (aOR 3.9, 95% CI 1.9–8.1), acute kidney injury (aOR 3.8, 95% CI 2.0–7.3), shock (aOR 3.7, 95% CI 1.7–8.1), and gastrointestinal hemorrhage (aOR 6.8, 95% CI 1.6–28.5). TLS was also linked to higher odds of requiring mechanical ventilation (aOR 5.2, 95% CI 2.3–11.5), vasopressors (aOR 5.7, 95% CI 2.4–13.3), and renal replacement therapy (aOR 8.8, 95% CI 1.8–43.8). TLS patients had longer hospital stays (21.5 vs. 16.7 days, p < 0.05; adjusted incidence rate ratio [aIRR] 1.2, 95% CI 1.0–1.5). There were no significant differences in the risks of sudden cardiac death, new-onset seizures, acute venous thromboembolism, immune effector cell-associated neurotoxicity, intracerebral hemorrhage, or disseminated intravascular coagulation. Mean hospitalization charges for CAR-T patients were $1,196,413, with no significant difference between groups. Conclusions: Our study found that CAR-T patients with TLS had higher odds of all-cause mortality, adverse outcomes, longer hospital stays, and increased need for intensive care. These findings highlight the importance of early TLS detection and management to reduce complications and optimize healthcare resource use.