Background: Chimeric antigen receptor (CAR)-T cell therapy is a transformative treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). While product efficacy and patient factors have been extensively studied, the impact of manufacturing logistics specifically the time interval between apheresis and CAR-T infusion on clinical outcomes remains unclear. Delays in cell processing may influence product fitness, tumor dynamics, and treatment-related toxicity.

Methods: We conducted a retrospective study of 95 patients with relapsed/refractory DLBCL treated with commercial CAR-T therapy at a tertiary cancer center from 2018 to 2023. We analyzed the association between time from apheresis to infusion (infusion delay) and clinical outcomes, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), progression-free survival (PFS), and overall survival (OS). Patients were stratified by infusion delay (≤30 days vs. >30 days). Survival analyses employed Kaplan-Meier estimates and Cox proportional hazards models. Multivariable models adjusted for age, sex, ECOG performance status, LDH, CAR-T product, and disease burden. Chi-square testing assessed associations between infusion delay and Grade ≥2 CRS incidence.

Results: Among 95 patients, the median age was 64 years (range 22–82). The median infusion delay was 39 days (range 6–116). CRS occurred in 59 (62.1%). Patients with infusion delays >30 days (n=68, 71%) had a higher incidence of CRS compared to those with delays ≤30 days (n=27, 29%). Among 40 patients developing Grade ≥2 CRS, 62.5% (25/40) had delays >30 days versus 37.5% (15/40) with shorter delays, though this difference did not reach statistical significance (Chi-square=2.67, p=0.10). ICANS rates were higher in the ≤30-day group (63%, 17/27) than the >30-day group (46%, 31/68), though not statistically significant (p=0.13). Longer infusion delays were associated with worse survival; median OS for the cohort was 14.8 months, with a significantly shorter median OS of 5 months in patients who experienced disease progression. Adjusted Cox modeling suggested a trend toward worse progression-free and overall survival in patients with longer infusion delays.

Conclusion: In this real-world cohort, longer infusion delays were associated with increased toxicity and poorer survival outcomes in relapsed/refractory DLBCL. Although a trend toward higher-grade CRS with delayed infusion was observed, the sample size limits definitive conclusions. These findings underscore the importance of optimizing manufacturing and logistic timelines to improve patient outcomes. Future larger-scale studies are warranted to validate these associations and inform clinical and operational practice.

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2025
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