National burden and outcomes of CAR-T therapy toxicities in DLBCL, multiple myeloma, and B-ALL: A retrospective analysis of the Nationwide Inpatient Sample.

Abstract

e19108 Background: Chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), and B-cell acute lymphoblastic leukemia (B-ALL). However, toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) complicate care and strain resources. Population-based estimates of toxicity rates across indications remain limited. We performed a national retrospective analysis to compare toxicity incidence and burden, aiming to inform risk stratification and resource planning. Methods: Using the Nationwide Inpatient Sample (NIS) 2020–2022, we identified adult hospitalizations receiving CAR-T for DLBCL, MM, or B-ALL (ICD-10 codes). We collected sociogeographic data, inpatient outcomes (mortality, length of stay [LOS], total charges), and complications including CRS, ICANS, sepsis, acute renal failure (ARF), and others. Analyses used Stata 18.5 with survey weighting. Multivariable logistic regression evaluated associations between indication and outcomes. p<0.05 was significant. Results: Among 10,650 CAR-T recipients, DLBCL (46.5%) and MM (19.6%) cohorts were older (mean age 62.7 and 63.6 years), whereas B-ALL (10.9%) patients were younger (mean 26 years). Median LOS was longest in B-ALL (19.2 days), followed by DLBCL (16.9) and MM (13.5; p<0.0001). Mean hospital charges were highest in DLBCL ($1,346,614), exceeding MM ($973,800) and B-ALL ($973,134; p<0.0001). Inpatient mortality was similar: MM 3.8%, B-ALL 3.0%, DLBCL 2.8% (p=0.61). CRS occurred in 47.1% overall, highest in MM (53.96%), then DLBCL (46.91%) and B-ALL (35.62%; p<0.001). On multivariable analysis, MM had higher odds of CRS vs. DLBCL (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 occurred in 14.7% overall, most in DLBCL (16.41%), then B-ALL (13.73%), and least in MM (11.03%; p=0.03). MM had lower odds vs. DLBCL (OR 0.63; 95%CI 0.45–0.90; p=0.01). Any complication was common across groups (MM 67.4%, DLBCL 66.0%, B-ALL 56.2%; p=0.01); B-ALL had lower adjusted odds vs. DLBCL (OR 0.66; 95%CI 0.50–0.89; p=0.006). ARF was most frequent in MM (21.6% vs. DLBCL 13.9%, B-ALL 9.4%; p<0.0001), with higher odds vs. DLBCL (OR 1.71; 95%CI 1.27–2.29; p=0.000). Rates of sepsis, mechanical ventilation, and vasopressor use did not differ significantly by indication. Conclusions: In this national cohort, CAR-T toxicities are common and confer substantial clinical and economic burden. DLBCL carries the highest costs; MM is associated with increased CRS and ARF but lower ICANS vs. DLBCL; and B-ALL, despite younger age and fewer complications, has the longest hospitalizations. These data support indication-specific toxicity mitigation, risk stratification, and resource planning as CAR-T use expands.