Burden and outcomes of CAR T-cell therapy toxicities in DLBCL, multiple myeloma, and B-ALL: A nationwide analysis

Abstract Background: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of blood cancers, resulting in long-lasting responses in diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), and B-cell acute lymphoblastic leukemia (B-ALL). However, serious toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) pose significant challenges for patient care and healthcare resources. Real-world, population-based data on toxicity rates and their effects across CAR-T uses are still limited. Therefore, this nationwide analysis aims to identify and compare the rates of these toxicities to improve risk assessment and resource planning. Methods: Using the Nationwide Inpatient Sample (NIS) database from 2020 to 2022, we identified hospitalizations for adults who received CAR-T therapy for DLBCL, MM, or B-ALL using the relevant ICD-10 codes. We gathered sociogeographic variables and examined inpatient outcomes, including complications such as mortality, CRS, ICANS, sepsis, acute renal failure (ARF), and others. All statistical analyses were performed with Stata 18.5, utilizing appropriate survey-weighting techniques. Multivariable logistic regression determined the independent association between CAR-T indication and outcomes. p<0.05 was considered statistically significant. Results: We identified 10,650 CAR-T recipients: DLBCL (46.5%), MM (19.6%), and B-ALL (10.9%). DLBCL and MM patients were mostly older, with mean ages of 62.7 and 63.6 years, respectively, compared to B-ALL patients at a mean age of 26 years. The median length of stay (LOS) was longest for B-ALL (19.2 days), followed by DLBCL (16.9 days), and MM (13.5 days; p<0.0001). DLBCL resulted in the highest mean hospital charges ($1,346,614), significantly higher than MM and B-ALL ($973,800 and $973,134, respectively; p<0.0001). Inpatient mortality rates were similar across the three groups: MM 3.8%, B-ALL 3.0%, and DLBCL 2.8% (p=0.61). CRS was observed in 47.1% of all CAR-T patients, most common in MM (53.96%), followed by DLBCL (46.91%), and B-ALL (35.62%; p<0.001). Multivariable regression showed that, compared to the DLBCL group, MM had higher odds of CRS (OR 1.33; 95% CI: 1.05–1.67; p=0.016), while B-ALL had lower odds (OR 0.63; 95%CI: 0.47–0.84; p=0.002). ICANS was present in 14.7% of patients, most frequently in DLBCL (16.41%), then B-ALL (13.73%), and least in MM (11.03%; p=0.03). Compared to DLBCL, MM patients had significantly lower odds of ICANS (OR 0.63; 95%CI: 0.45–0.90; p=0.01). Complications were common across all groups, MM 67.4%, DLBCL 66.0%, B-ALL 56.2%; p=0.01, although B-ALL patients had lower adjusted odds of complications than DLBCL (OR 0.66; 95%CI: 0.50–0.89; p=0.006). MM patients experienced the highest ARF rate (21.6% vs. DLBCL's 13.9% and B-ALL's 9.4%; p<0.0001) and significantly higher odds of ARF compared to DLBCL (OR 1.71; 95%CI: 1.27–2.29; p=0.000). The rates of sepsis, mechanical ventilation, and vasopressor use did not significantly differ among these groups. Conclusion: In this large, nationally representative cohort, CAR-T toxicities remain common and impose a significant clinical and economic burden. DLBCL patients incurred the highest costs, and MM patients are at increased risk for CRS and ARF but have lower odds of ICANS compared to DLBCL. B-ALL patients, while younger and with fewer complications, experienced longer hospital stays. Our findings underscore the urgent need for improved toxicity mitigation strategies, risk stratification, and resource planning tailored to disease type as CAR-T therapy use expands.