Association of Flu AUC and clinical outcomes after ide-cel treatment
Sweiss K, Wagner C, Anto E, et al. Fludarabine Lymphodepletion Exposure Is Associated With Toxicities After Idecabtagene-Vicleucel in Relapsed/Refractory Multiple Myeloma: Real-World Experience from the US Myeloma Immunotherapy Consortium. Transplantation and Cellular Therapy. 2025; (doi: 10.1016/j.jtct.2025.08.015).
Researchers report that exposure to fludarabine (Flu), a component of lymphodepletion chemotherapy, may influence toxicity in patients undergoing treatment with idecabtagene-vicleucel (ide-cel). The real-world study, which leveraged data from the U.S. Multiple Myeloma Immunotherapy Consortium, analyzed outcomes in 285 patients with relapsed or refractory multiple myeloma who were apheresed for the chimeric antigen receptor (CAR) T-cell therapy by December 31, 2022. Per usual practice, body surface area (BSA) determines Flu dosage for the pre-infusion lymphodepletion process; however, the BSA approach increases the likelihood of overexposure, which subsequently elevates the risk for CAR-T toxicity. In the study population, the researchers observed an association between high levels of cumulative Flu exposure, as defined by area under the concentration-time curve (AUC), and development of immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, and other toxicities after ide-cel treatment. The findings suggest that Flu AUC could be a modifiable variable for predicting response after CAR T therapy and that optimizing exposure via individualized dosing has the potential to limit treatment-related toxicities.