Prophylactic dexamethasone at the time of absolute lymphocyte expansion does not mitigate risk or event-free survival...

High post-infusion absolute lymphocyte count (ALC) following ciltacabtagene autoleucel (cilta-cel) therapy is associated with an increased risk of immune effector cell-associated delayed neurotoxicity (IEC-DNT), including parkinsonism (IEC-PKS) and cranial nerve palsies (IEC-NP). Between December 2024 and August 2025, we evaluated a prophylactic strategy using a short course of dexamethasone (DEX) in 57 patients with high-ALC, defined as a post-infusion ALC of ≥3 × 10⁹/L on serial monitoring after CAR-T infusion. DEX was administered at 10 mg twice daily for a minimum of three days. Outcomes were compared with a historical control cohort of 104 patients with high-ALC treated between February 2022 and November 2024. While DEX appeared to attenuate the severity of facial nerve palsy, it did not significantly improve event-free survival for IEC-DNT, IEC-PKS, or IEC-NP, nor did it reduce the severity of IEC-PKS. Analysis of ALC kinetics demonstrated no statistically or biologically meaningful reduction in lymphocyte expansion, suggesting that the dose and duration of dexamethasone may be insufficient, or that additional immune and host factors contribute to the risk of IEC-DNT. These findings highlight the limited role of corticosteroid prophylaxis and underscore the need for more mechanistically targeted strategies to mitigate this challenging complication of BCMA-directed CAR-T therapy.