Assessing the utility of the charlson comorbidity index in predicting outcomes of CAR-T therapy in patients with diffuse large B-cell lymphoma

Abstract Background: The Charlson Comorbidity Index (CCI) is a widely used tool for assessing comorbidity burden and predicting clinical outcomes, yet its prognostic value in the setting of chimeric antigen receptor T-cell (CAR-T) therapy for diffuse large B-cell lymphoma (DLBCL) has not been well established. As CAR-T therapy expands to broader patient populations, understanding the influence of baseline comorbidity burden is critical to inform risk stratification and patient selection. Methods We conducted a weighted retrospective analysis using the National Inpatient Sample (2016–2022) to evaluate outcomes of adult patients hospitalized for CAR-T therapy for DLBCL. Patients were stratified by CCI scores into three groups: 2 (reference group), 3, and ≥4. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay (LOS), total hospital charges, receipt of packed red blood cell (PRBC) transfusions, and inpatient complications including acute kidney injury (AKI), immune effector cell-associated neurotoxicity syndrome (ICANS), febrile neutropenia, pulmonary embolism (PE), deep vein thrombosis (DVT), mechanical ventilation, cytokine release syndrome (CRS), and septic shock. Multivariable logistic and linear regression models were used to assess outcomes, adjusted for demographics, hospital characteristics, and clinical covariates. Results The final cohort included 4,385 CAR-T hospitalizations. CCI scores were distributed as follows: 54.7% had a score of 2, 21.3% had a score of 3, and 23.9% had a score of 4 or higher. In-hospital mortality increased with higher CCI scores: 2.29% for CCI 2, 5.34% for CCI 3, and 5.71% for CCI ≥4. Compared to CCI 2, the adjusted odds ratio (aOR) for mortality was 2.51 for CCI 3 (p = 0.056) and 2.64 for CCI ≥4 (p = 0.03). Higher CCI scores were also associated with longer hospitalizations, with adjusted increases in LOS of 3.03 days for CCI 3 (p = 0.026) and 6.26 days for CCI ≥4 (p < 0.001). Total hospital charges trended higher with comorbidity burden, with adjusted increases of $184,882 for CCI 3 (p = 0.064) and $159,562 for CCI ≥4 (p = 0.108). Complications were more frequent among patients with higher CCI. Compared to CCI 2, AKI increased by 84.6% for CCI 3 (p = 0.056) and 280.4% for CCI ≥4 (p < 0.001). ICANS increased by 62.4% (p = 0.065) for CCI 3 and 67.7% (p = 0.054) for CCI ≥4, representing a trend toward statistical significance. The need for mechanical ventilation increased by 366.3% for CCI 3 (p = 0.004) and 559.8% for CCI ≥4 (p < 0.001). Other notable findings included increased risk of new PE (CCI 3: +476.3%, p = 0.016), DVT (CCI 3: +353.7%, p = 0.032), and PRBC transfusion (CCI ≥4: +96.2%, p = 0.017). No statistically significant differences were observed across groups for febrile neutropenia, CRS, or septic shock.Conclusion: Higher Charlson Comorbidity Index scores are associated with increased mortality, prolonged hospitalizations, greater healthcare costs, and more frequent inpatient complications among DLBCL patients receiving CAR-T therapy. Although ICANS showed a trend toward higher incidence with increasing CCI, it did not reach statistical significance. These findings suggest that CCI may be a valuable tool for risk stratification and pre-treatment decision-making in this high-risk population.