Dexamethasone prophylaxis for excessive lymphocyte expansion after cilta-cel in multiple myeloma

Increased absolute lymphocyte count (ALC) appears to be a predictor of risk for both treatment-related mortality and atypical neurologic events among patients receiving chimeric antigen receptor (CAR)-T cell therapies for relapsed/refractory multiple myeloma. In this study we analyzed clinical outcomes of patients treated with the CAR-T cell therapy ciltacabtagene autoleucel (cilta-cel) at the Colorado Blood Cancer Institute, from September 2023 to January 2025. Baseline demographics, disease characteristics, and clinical data were collected before and after CAR-T therapy. Patients were stratified into 2 groups: pre-intervention (patients treated September 2023-July 2024) and intervention (patients treated August 2024-January 2025; those with ALC 5000/μL received 3 days of dexamethasone prophylaxis on first identification of elevated ALC). In the pre-intervention group, 9/30 patients had peak ALC 5000/μL; 5/9 (55.6%) experienced atypical neurologic events and all 5 died (post-cilta-cel-related complications). In the intervention group, 7/23 patients had peak ALC 5000/μL and received dexamethasone; 1/7 had an atypical neurologic event; and there was 1 death (infectious complication, 9 months post-treatment). Dexamethasone prophylaxis in patients with ALC 5000/μL resulted in rapid ALC reduction. Overall survival (OS) was significantly lower in pre-intervention patients with ALC 5000/μL compared with intervention patients with ALC 5000/μL and patients with ALC ≤5000/μL (P=.0013). ALC 5000/μL (vs ALC ≤5000/μL) was significantly associated with atypical neurologic events (odds ratio 6.8, P=.0157) and lower OS (hazard ratio 6.2, P=.0106). In conclusion, ALC 5000/μL after cilta-cel treatment predicted severe early neurologic events and high mortality risk. Dexamethasone prophylaxis demonstrated promise for risk mitigation.