Impact of Chronic Kidney Disease on Toxicity Patterns and Economic Burden in CAR T‑Cell Therapy for Multiple Myeloma: A National Analysis

Chronic kidney disease (CKD) may impair physiologic resilience during chimeric antigen receptor (CAR) T‑cell therapy for multiple myeloma (MM). While cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndromes (ICANS) have been described in MM CAR‑T recipients with CKD, the broader cardiopulmonary, infectious, renal, and economic implications of CKD remain insufficiently defined. We examined the national impact of CKD3a+ on mortality, immune‑effector toxicities, organ dysfunction, infections and resource utilization.

Adult MM hospitalizations receiving CAR T‑cell therapy were identified from the National Inpatient Sample (2018–2022) using ICD‑10‑PCS codes. Patients with ESRD were excluded. CKD was categorized as CKD3a+ (eGFR <60 mL/min) versus no CKD/CKD1–2. Outcomes included in‑hospital mortality, CRS (2021–2022), ICANS (2022), arrhythmias, acute kidney injury (AKI), renal replacement therapy, acute respiratory failure, infections and total hospitalization cost. Comparative analyses used chi‑square testing. Multivariable regression adjusted for demographics, comorbidities, and hospital characteristics.

Among 2,045 weighted MM CAR‑T hospitalizations, 7.6% had CKD3a+. Overall CRS rates were similar (66.7% vs 64.9%; p=0.839) between CKD3a+ vs no/CKD1-2. Overall ICANS rates were also comparable (16.7% vs 17.3%; p=0.941). Differences in CRS/ICANS grades were not significant. CKD3a+ patients experienced sharply higher AKI (58.1% vs 13.0%; p<0.001; adjusted Odds ratio [OR] 9.2, p<0.001). Renal replacement therapy was more frequent in CKD3a+ but not statistically significant (3.2% vs 0.8%; p=0.196). Acute respiratory failure was more frequent (9.7% vs 2.9%; p=0.045) in patients with CKD. Arrhythmias were numerically higher but non‑significant (25.8% vs 20.6%; p=0.527; adjusted OR 1.3, 95% CI 0.4–4.9; p=0.673). Infections were amplified, including gram‑negative bacteremia (3.2% vs 0.3%; p=0.026), sepsis (9.7% vs 2.6%; p=0.040), and septic shock (3.2% vs 0.3%; p=0.027) in patients with CKD. Inpatient mortality was numerically higher (6.5% vs 1.9%; p=0.101), though nonsignificant after adjustment (OR 6.9; p=0.319). Hospital costs were substantially higher in CKD3a+ (USD 346,769 vs 239,175; p=0.006), though not significant in adjusted models (OR 1.3; p=0.120).

CKD3a+ is associated with markedly increased AKI, higher respiratory failure and infections, with a trend towards higher hospitalization costs. Inpatient mortality, CRS and ICANS rates were similar. CKD3a+ represents a significant vulnerability that amplifies downstream complications in MM CAR‑T recipients, warranting enhanced pre‑treatment risk stratification, infection surveillance, and renal‑preserving strategies.