Background: Peripherally inserted central catheter (PICC) is the most commonly utilized central venous access for chimeric antigen receptor T-cell therapy (CART) infusion, due to hypothetical concern that the angled needle of a Port may enact shear stress on CAR T-cells. However, it has never been demonstrated whether there exists a difference in safety and/or efficacy outcomes among CART recipients depending on method of central venous access.

Methods: This is a single-center retrospective study including adult large B-cell lymphoma patients who received standard of care anti-CD19 autologous CART between January 2018 and March 2025. Baseline characteristics were collected before initiation of lymphodepleting chemotherapy. Cytokine release syndrome (CRS) and immune effector cell associated syndrome (ICANS) were prospectively graded according to ASTCT criteria. Response was assessed by Lugano 2014 Criteria. CAR T-cell levels in peripheral blood were measured on day +7 after infusion using a flow cytometry assay based on antibody targeting FMC63 domain of anti-CD19 CAR T cells, as these levels have been reported to be associated with response to CAR T therapy (Blumenberg et al. Blood Adv 2023).

Results: Five-hundred and four patients were included in the analysis: 202 (40.0%) received CART via Port, 302 (60.0%) via PICC line or central venous catheter (CVC). No differences in baseline characteristics were observed between the 2 groups (including age, sex, histology, Eastern Cooperative Oncology Group performance status, International Prognostic Index score, CART product, serum lactate dehydrogenase levels, serum c-reactive protein levels, or serum ferritin), except for a higher rate of previously refractory disease in patients who received CART via Port (76.2% vs 68.1%, p=0.048). No differences in safety outcomes, including CRS of any grade (88.6% vs 86.8%, p=0.536), grade (G) 3-4 CRS (13.9% vs 11.6%, p=0.450), ICANS of any grade (60.9% vs 53.0%, p=0.079), G3-4 ICANS (38.1% vs 33.1%, p=0.249), infections of any grade (5.0% vs 4.6%, p=0.871) and day 30 G3-4 cytopenia (49.0% vs 57.6%, p=0.103), were observed between the 2 groups, except for a significantly higher rate of venous thromboembolic events among patients who received CART via PICC line/CVC (3.0% vs 9.3%, p=0.0057). No significant differences in day 30 (52.2% vs 56.7%, p=0.325) and day 90 (46.1% vs 50.5%, p=0.351) complete response rates were observed between the 2 groups. After a median follow-up of 18.0 months (95% confidence interval, 13.9-23.7 months), no significant differences in median progression-free survival (5.59 vs 6.67 months, p=0.25) and median overall survival (13.7 vs 23.6 months, p=0.13) were observed between the 2 groups. Day +7 CAR T-cell levels in peripheral blood were available in 128 patients (49 with Port, 79 with PICC/CVC), with no significant difference in baseline characteristics when comparing the 2 groups. No significant difference in median CAR T-cells amplification was observed between the 2 groups (56 vs 59 CAR+ T-cells/mL, p=0.992).

Conclusion: This retrospective cohort study is the first to compare implanted Port to PICC line/CVC for CART administration in adult patients with LBCL. Our findings demonstrate that the use of Port, more commonly present in patients with refractory disease, is associated with comparable safety, efficacy and CAR T-cell amplification to PICC/CVC, while conferring a lower risk of venous thromboembolism. These results do not support concerns regarding potential mechanistic limitations related to CAR-T cell fragility during Port-based infusion.

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2025
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