Background and Importance According to an American study¹, prior exposure to Piperacillin/tazobactam (P/T), Imipenem/cilastatin (I) and meropenem (M) is correlated with reduced overall survival and a 71% higher risk of death in patients treated with CAR-T cells (Chimeric Antigen Receptor T cells). This exposure is also associated with an increased risk of immune effector cell-associated neurotoxicity syndrome (ICANS).

Aim and Objectives The aim is to demonstrate if the American results apply to our real-life results.

Material and Methods For each patient who received a CAR-T cells injection between January 2019 and August 2023, the ‘CAR-T cells’ pharmaceutical team checked: antibiotic prescription 4 weeks prior to CAR-T cells injection, post-injection toxicities (ICANS and cytokine release syndrome (CRS)) and death within 6 months of CAR-T cells injection.

To have populations comparable to those in the study, we defined two groups: ‘P/T/I/M’ is patients who received P/T/I/M antibiotics, and ‘Other antibiotics and naive’ is patients who received antibiotics other than P/T/I/M or antibiotic naive. we selected all CAR-T cells with marketing authorisation.

Statistical comparisons were made using the Fischer test (risk = 5% bilateral).

Results Two-hundred and five patients received CAR-T cells: 172 ‘Other ATB and naive’ patients (84%) and 33 ‘P/T/I/M’ patients (16%) in the 4 weeks prior to injection.

In the ‘P/T/I/M’ population, there were 12 CRS (36.5%), 0 ICANS, 12 ICANS+CRS (36.5%) and 9 (27%) without toxicities. Seven (21%) patients died.

In the ‘Other antibiotics and naive’ population, there were 100 CRS (58%), 2 ICANS (1%), 43 ICANS+CRS (25%) and 27 no toxicities (16%). Twenty-four patients (14%) died.

A higher risk of CRS has been identified in the ‘P/T/I/M’ group (p=0.02).

No other significant difference was found between the 2 groups on: ICANS+CRS (p=0.2), ICANS (p=1), or death (p=0.29).

Conclusion and Relevance Our study shows a higher risk of CRS for patients exposed to P/T/I/M 4 weeks prior to injection.

Our study also shows no excess risk of ICANS nor toxicities and death for ‘P/T/I/M’ patients. Our results are therefore not similar to those of the American study.

These differences could be explained by the size of our population and the fact that the American study only selected anti-CD19 CAR-T cells.

References and/or Acknowledgements 1. https://doi.org/10.1038/s41591-022-01702-9

Conflict of Interest No conflict of interest.